Post menopausal osteoporosis
Submitted by-Amit KochharBOT 2nd yearPt DDU IPH
Osteoporosis
PATHOGENESIS
DIAGNOSIS
TREATMENT
Two components of the bone
Cortical Bone Dense and compact Runs the length of the long bones forming a
hollow cylinder
Trabecular bone Has a light honeycomb structure Trabeculae are arranged in the directions of tension
and compression Occurs in the heads of the long bones Also makes up most of the bone in the vertebrae
Osteons
Principal organizing feature of compact bone Haversian canal ndash place for the nerve blood
and lymphatic vessels Lamellae ndash collagen deposition pattern Lacunae ndash holes for osteocytes Canaliculi ndash place of communication between
osteocytes
Bone cells
Osteocytes - derived from osteoprogenitor cells Osteoblasts Osteoclasts
Osteocytes
Trapped osteoblasts1048708 In lacunae
Keep bone matrix in good condition and can release calcium ions from bone matrix when calcium demands increase1048708 Osteocytic osteolysis
Osteoblasts
Make collagenActivate nucleation of hydroxyapatite
crystallization onto the collagen matrix forming new bone
As they become enveloped by the collagenous matrix they produce they transform into osteocytes
Stimulate osteoclast resorptive activity
Osteoclasts
Resorbe bone matrix from sites where it is deteriorating or not needed
Digest bone matrix componentsFocal decalcification and extracellular
digestion by acid hydrolases and uptake of digested material
Disappear after resorptionAssist with mineral homeostasis
Chemistry of the bone
Matrix Mineral
Matrix - osteoid
Collagen type I and IVLayers of various orientations (add to the
strength of the matrix)Other proteins 10 of the bone protein
1048708 Direct formation of fibers1048708 Enhance mineralization1048708 Provide signals for remodeling
Mineral
A calcium phosphatecarbonate compound resembling the mineral hydroxyapatite Ca10(PO4)6(OH)2
1048708 Hydroxyapatite crystals1048708 Imperfect1048708 Contain Mg Na K
Mineralization of the bone
Calcification occurs by extracellular deposition of hydroxyapatite crystalsTrapping of calcium and phosphate ions in
concentrations that would initiate deposition of calcium phosphate in the solid phase followed by its conversion to crystalline hydroxyapatite
Mechanisms exist to both initiate and inhibit calcification
Bone remodeling process
Proceeds in cycles ndash first resorption than bone formation
The calcium content of bone turns over with a half-life of 1-5 years
Bone remodeling process
Coordination of Resorption and Formation
Phase ISignal from osteoblastsStimulation of osteoblastic precursor cells to
become osteoclastsProcess takes 10 days
Coordination of Resorption and Formation
Phase IIOsteoclast resorb bone creating cavity1048708 Macrophages clean up
Phase III1048708 New bone laid down by osteoblasts1048708 Takes 3 months
Pathways of differentiation ofosteoclasts and osteoblasts
Hormonal Influence
Vitamin DParathyroid HormoneCalcitoninEstrogenAndrogen
Vitamin D
Osteoblast have receptors for (125-(OH)2-D) Increases activity of both osteoblasts and
osteoclasts Increases osteocytic osteolysis (remodeling) Increases mineralization through increased
intestinal calcium absorption Feedback action of (125-(OH)2-D) represses
gene for PTH synthesis
Parathyroid Hormone
Accelerates removal of calcium from bone to increase Ca levels in blood
PTH receptors present on both osteoblasts and osteoclasts
Osteoblasts respond to PTH by Change of shape and cytoskeletal arrangement Inhibition of collagen synthesis Stimulation of IL-6 macrophage colony-stimulating factor
secretion Chronic stimulation of the PTH causes hypocalcemia
and leads to resorptive effects of PTH on bone
Calcitonin
C cells of thyroid gland secrete calcitoninStraight chain peptide - 32 aaSynthesized from a large preprohormoneRise in plasma calcium is major stimulus
of calcitonin secretionPlasma concentration is 10-20 pgml and
half life is 5 min
Actions of Calcitonin
Osteoclasts are target cells for calcitoninMajor effect of clacitonin is rapid fall of
plasma calcium concentration caused by inhibition of bone resorption
Magnitude of decrease is proportional to the baseline rate of bone turnover
Other systemic hormones
Estrogens Increase bone remodeling
Androgens Increase bone formation
Other systemic hormones
Growth hormone Increases bone remodeling
Glucocorticoids Inhibit bone formation
Thyroid hormones Increase bone resorption Increase bone formation
Local regulators of bone remodeling
Cytokines IL-6 IL-1
ProstaglandinsGrowth factors
IGF-ITGF-β
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Osteoporosis
PATHOGENESIS
DIAGNOSIS
TREATMENT
Two components of the bone
Cortical Bone Dense and compact Runs the length of the long bones forming a
hollow cylinder
Trabecular bone Has a light honeycomb structure Trabeculae are arranged in the directions of tension
and compression Occurs in the heads of the long bones Also makes up most of the bone in the vertebrae
Osteons
Principal organizing feature of compact bone Haversian canal ndash place for the nerve blood
and lymphatic vessels Lamellae ndash collagen deposition pattern Lacunae ndash holes for osteocytes Canaliculi ndash place of communication between
osteocytes
Bone cells
Osteocytes - derived from osteoprogenitor cells Osteoblasts Osteoclasts
Osteocytes
Trapped osteoblasts1048708 In lacunae
Keep bone matrix in good condition and can release calcium ions from bone matrix when calcium demands increase1048708 Osteocytic osteolysis
Osteoblasts
Make collagenActivate nucleation of hydroxyapatite
crystallization onto the collagen matrix forming new bone
As they become enveloped by the collagenous matrix they produce they transform into osteocytes
Stimulate osteoclast resorptive activity
Osteoclasts
Resorbe bone matrix from sites where it is deteriorating or not needed
Digest bone matrix componentsFocal decalcification and extracellular
digestion by acid hydrolases and uptake of digested material
Disappear after resorptionAssist with mineral homeostasis
Chemistry of the bone
Matrix Mineral
Matrix - osteoid
Collagen type I and IVLayers of various orientations (add to the
strength of the matrix)Other proteins 10 of the bone protein
1048708 Direct formation of fibers1048708 Enhance mineralization1048708 Provide signals for remodeling
Mineral
A calcium phosphatecarbonate compound resembling the mineral hydroxyapatite Ca10(PO4)6(OH)2
1048708 Hydroxyapatite crystals1048708 Imperfect1048708 Contain Mg Na K
Mineralization of the bone
Calcification occurs by extracellular deposition of hydroxyapatite crystalsTrapping of calcium and phosphate ions in
concentrations that would initiate deposition of calcium phosphate in the solid phase followed by its conversion to crystalline hydroxyapatite
Mechanisms exist to both initiate and inhibit calcification
Bone remodeling process
Proceeds in cycles ndash first resorption than bone formation
The calcium content of bone turns over with a half-life of 1-5 years
Bone remodeling process
Coordination of Resorption and Formation
Phase ISignal from osteoblastsStimulation of osteoblastic precursor cells to
become osteoclastsProcess takes 10 days
Coordination of Resorption and Formation
Phase IIOsteoclast resorb bone creating cavity1048708 Macrophages clean up
Phase III1048708 New bone laid down by osteoblasts1048708 Takes 3 months
Pathways of differentiation ofosteoclasts and osteoblasts
Hormonal Influence
Vitamin DParathyroid HormoneCalcitoninEstrogenAndrogen
Vitamin D
Osteoblast have receptors for (125-(OH)2-D) Increases activity of both osteoblasts and
osteoclasts Increases osteocytic osteolysis (remodeling) Increases mineralization through increased
intestinal calcium absorption Feedback action of (125-(OH)2-D) represses
gene for PTH synthesis
Parathyroid Hormone
Accelerates removal of calcium from bone to increase Ca levels in blood
PTH receptors present on both osteoblasts and osteoclasts
Osteoblasts respond to PTH by Change of shape and cytoskeletal arrangement Inhibition of collagen synthesis Stimulation of IL-6 macrophage colony-stimulating factor
secretion Chronic stimulation of the PTH causes hypocalcemia
and leads to resorptive effects of PTH on bone
Calcitonin
C cells of thyroid gland secrete calcitoninStraight chain peptide - 32 aaSynthesized from a large preprohormoneRise in plasma calcium is major stimulus
of calcitonin secretionPlasma concentration is 10-20 pgml and
half life is 5 min
Actions of Calcitonin
Osteoclasts are target cells for calcitoninMajor effect of clacitonin is rapid fall of
plasma calcium concentration caused by inhibition of bone resorption
Magnitude of decrease is proportional to the baseline rate of bone turnover
Other systemic hormones
Estrogens Increase bone remodeling
Androgens Increase bone formation
Other systemic hormones
Growth hormone Increases bone remodeling
Glucocorticoids Inhibit bone formation
Thyroid hormones Increase bone resorption Increase bone formation
Local regulators of bone remodeling
Cytokines IL-6 IL-1
ProstaglandinsGrowth factors
IGF-ITGF-β
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Two components of the bone
Cortical Bone Dense and compact Runs the length of the long bones forming a
hollow cylinder
Trabecular bone Has a light honeycomb structure Trabeculae are arranged in the directions of tension
and compression Occurs in the heads of the long bones Also makes up most of the bone in the vertebrae
Osteons
Principal organizing feature of compact bone Haversian canal ndash place for the nerve blood
and lymphatic vessels Lamellae ndash collagen deposition pattern Lacunae ndash holes for osteocytes Canaliculi ndash place of communication between
osteocytes
Bone cells
Osteocytes - derived from osteoprogenitor cells Osteoblasts Osteoclasts
Osteocytes
Trapped osteoblasts1048708 In lacunae
Keep bone matrix in good condition and can release calcium ions from bone matrix when calcium demands increase1048708 Osteocytic osteolysis
Osteoblasts
Make collagenActivate nucleation of hydroxyapatite
crystallization onto the collagen matrix forming new bone
As they become enveloped by the collagenous matrix they produce they transform into osteocytes
Stimulate osteoclast resorptive activity
Osteoclasts
Resorbe bone matrix from sites where it is deteriorating or not needed
Digest bone matrix componentsFocal decalcification and extracellular
digestion by acid hydrolases and uptake of digested material
Disappear after resorptionAssist with mineral homeostasis
Chemistry of the bone
Matrix Mineral
Matrix - osteoid
Collagen type I and IVLayers of various orientations (add to the
strength of the matrix)Other proteins 10 of the bone protein
1048708 Direct formation of fibers1048708 Enhance mineralization1048708 Provide signals for remodeling
Mineral
A calcium phosphatecarbonate compound resembling the mineral hydroxyapatite Ca10(PO4)6(OH)2
1048708 Hydroxyapatite crystals1048708 Imperfect1048708 Contain Mg Na K
Mineralization of the bone
Calcification occurs by extracellular deposition of hydroxyapatite crystalsTrapping of calcium and phosphate ions in
concentrations that would initiate deposition of calcium phosphate in the solid phase followed by its conversion to crystalline hydroxyapatite
Mechanisms exist to both initiate and inhibit calcification
Bone remodeling process
Proceeds in cycles ndash first resorption than bone formation
The calcium content of bone turns over with a half-life of 1-5 years
Bone remodeling process
Coordination of Resorption and Formation
Phase ISignal from osteoblastsStimulation of osteoblastic precursor cells to
become osteoclastsProcess takes 10 days
Coordination of Resorption and Formation
Phase IIOsteoclast resorb bone creating cavity1048708 Macrophages clean up
Phase III1048708 New bone laid down by osteoblasts1048708 Takes 3 months
Pathways of differentiation ofosteoclasts and osteoblasts
Hormonal Influence
Vitamin DParathyroid HormoneCalcitoninEstrogenAndrogen
Vitamin D
Osteoblast have receptors for (125-(OH)2-D) Increases activity of both osteoblasts and
osteoclasts Increases osteocytic osteolysis (remodeling) Increases mineralization through increased
intestinal calcium absorption Feedback action of (125-(OH)2-D) represses
gene for PTH synthesis
Parathyroid Hormone
Accelerates removal of calcium from bone to increase Ca levels in blood
PTH receptors present on both osteoblasts and osteoclasts
Osteoblasts respond to PTH by Change of shape and cytoskeletal arrangement Inhibition of collagen synthesis Stimulation of IL-6 macrophage colony-stimulating factor
secretion Chronic stimulation of the PTH causes hypocalcemia
and leads to resorptive effects of PTH on bone
Calcitonin
C cells of thyroid gland secrete calcitoninStraight chain peptide - 32 aaSynthesized from a large preprohormoneRise in plasma calcium is major stimulus
of calcitonin secretionPlasma concentration is 10-20 pgml and
half life is 5 min
Actions of Calcitonin
Osteoclasts are target cells for calcitoninMajor effect of clacitonin is rapid fall of
plasma calcium concentration caused by inhibition of bone resorption
Magnitude of decrease is proportional to the baseline rate of bone turnover
Other systemic hormones
Estrogens Increase bone remodeling
Androgens Increase bone formation
Other systemic hormones
Growth hormone Increases bone remodeling
Glucocorticoids Inhibit bone formation
Thyroid hormones Increase bone resorption Increase bone formation
Local regulators of bone remodeling
Cytokines IL-6 IL-1
ProstaglandinsGrowth factors
IGF-ITGF-β
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Osteons
Principal organizing feature of compact bone Haversian canal ndash place for the nerve blood
and lymphatic vessels Lamellae ndash collagen deposition pattern Lacunae ndash holes for osteocytes Canaliculi ndash place of communication between
osteocytes
Bone cells
Osteocytes - derived from osteoprogenitor cells Osteoblasts Osteoclasts
Osteocytes
Trapped osteoblasts1048708 In lacunae
Keep bone matrix in good condition and can release calcium ions from bone matrix when calcium demands increase1048708 Osteocytic osteolysis
Osteoblasts
Make collagenActivate nucleation of hydroxyapatite
crystallization onto the collagen matrix forming new bone
As they become enveloped by the collagenous matrix they produce they transform into osteocytes
Stimulate osteoclast resorptive activity
Osteoclasts
Resorbe bone matrix from sites where it is deteriorating or not needed
Digest bone matrix componentsFocal decalcification and extracellular
digestion by acid hydrolases and uptake of digested material
Disappear after resorptionAssist with mineral homeostasis
Chemistry of the bone
Matrix Mineral
Matrix - osteoid
Collagen type I and IVLayers of various orientations (add to the
strength of the matrix)Other proteins 10 of the bone protein
1048708 Direct formation of fibers1048708 Enhance mineralization1048708 Provide signals for remodeling
Mineral
A calcium phosphatecarbonate compound resembling the mineral hydroxyapatite Ca10(PO4)6(OH)2
1048708 Hydroxyapatite crystals1048708 Imperfect1048708 Contain Mg Na K
Mineralization of the bone
Calcification occurs by extracellular deposition of hydroxyapatite crystalsTrapping of calcium and phosphate ions in
concentrations that would initiate deposition of calcium phosphate in the solid phase followed by its conversion to crystalline hydroxyapatite
Mechanisms exist to both initiate and inhibit calcification
Bone remodeling process
Proceeds in cycles ndash first resorption than bone formation
The calcium content of bone turns over with a half-life of 1-5 years
Bone remodeling process
Coordination of Resorption and Formation
Phase ISignal from osteoblastsStimulation of osteoblastic precursor cells to
become osteoclastsProcess takes 10 days
Coordination of Resorption and Formation
Phase IIOsteoclast resorb bone creating cavity1048708 Macrophages clean up
Phase III1048708 New bone laid down by osteoblasts1048708 Takes 3 months
Pathways of differentiation ofosteoclasts and osteoblasts
Hormonal Influence
Vitamin DParathyroid HormoneCalcitoninEstrogenAndrogen
Vitamin D
Osteoblast have receptors for (125-(OH)2-D) Increases activity of both osteoblasts and
osteoclasts Increases osteocytic osteolysis (remodeling) Increases mineralization through increased
intestinal calcium absorption Feedback action of (125-(OH)2-D) represses
gene for PTH synthesis
Parathyroid Hormone
Accelerates removal of calcium from bone to increase Ca levels in blood
PTH receptors present on both osteoblasts and osteoclasts
Osteoblasts respond to PTH by Change of shape and cytoskeletal arrangement Inhibition of collagen synthesis Stimulation of IL-6 macrophage colony-stimulating factor
secretion Chronic stimulation of the PTH causes hypocalcemia
and leads to resorptive effects of PTH on bone
Calcitonin
C cells of thyroid gland secrete calcitoninStraight chain peptide - 32 aaSynthesized from a large preprohormoneRise in plasma calcium is major stimulus
of calcitonin secretionPlasma concentration is 10-20 pgml and
half life is 5 min
Actions of Calcitonin
Osteoclasts are target cells for calcitoninMajor effect of clacitonin is rapid fall of
plasma calcium concentration caused by inhibition of bone resorption
Magnitude of decrease is proportional to the baseline rate of bone turnover
Other systemic hormones
Estrogens Increase bone remodeling
Androgens Increase bone formation
Other systemic hormones
Growth hormone Increases bone remodeling
Glucocorticoids Inhibit bone formation
Thyroid hormones Increase bone resorption Increase bone formation
Local regulators of bone remodeling
Cytokines IL-6 IL-1
ProstaglandinsGrowth factors
IGF-ITGF-β
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Bone cells
Osteocytes - derived from osteoprogenitor cells Osteoblasts Osteoclasts
Osteocytes
Trapped osteoblasts1048708 In lacunae
Keep bone matrix in good condition and can release calcium ions from bone matrix when calcium demands increase1048708 Osteocytic osteolysis
Osteoblasts
Make collagenActivate nucleation of hydroxyapatite
crystallization onto the collagen matrix forming new bone
As they become enveloped by the collagenous matrix they produce they transform into osteocytes
Stimulate osteoclast resorptive activity
Osteoclasts
Resorbe bone matrix from sites where it is deteriorating or not needed
Digest bone matrix componentsFocal decalcification and extracellular
digestion by acid hydrolases and uptake of digested material
Disappear after resorptionAssist with mineral homeostasis
Chemistry of the bone
Matrix Mineral
Matrix - osteoid
Collagen type I and IVLayers of various orientations (add to the
strength of the matrix)Other proteins 10 of the bone protein
1048708 Direct formation of fibers1048708 Enhance mineralization1048708 Provide signals for remodeling
Mineral
A calcium phosphatecarbonate compound resembling the mineral hydroxyapatite Ca10(PO4)6(OH)2
1048708 Hydroxyapatite crystals1048708 Imperfect1048708 Contain Mg Na K
Mineralization of the bone
Calcification occurs by extracellular deposition of hydroxyapatite crystalsTrapping of calcium and phosphate ions in
concentrations that would initiate deposition of calcium phosphate in the solid phase followed by its conversion to crystalline hydroxyapatite
Mechanisms exist to both initiate and inhibit calcification
Bone remodeling process
Proceeds in cycles ndash first resorption than bone formation
The calcium content of bone turns over with a half-life of 1-5 years
Bone remodeling process
Coordination of Resorption and Formation
Phase ISignal from osteoblastsStimulation of osteoblastic precursor cells to
become osteoclastsProcess takes 10 days
Coordination of Resorption and Formation
Phase IIOsteoclast resorb bone creating cavity1048708 Macrophages clean up
Phase III1048708 New bone laid down by osteoblasts1048708 Takes 3 months
Pathways of differentiation ofosteoclasts and osteoblasts
Hormonal Influence
Vitamin DParathyroid HormoneCalcitoninEstrogenAndrogen
Vitamin D
Osteoblast have receptors for (125-(OH)2-D) Increases activity of both osteoblasts and
osteoclasts Increases osteocytic osteolysis (remodeling) Increases mineralization through increased
intestinal calcium absorption Feedback action of (125-(OH)2-D) represses
gene for PTH synthesis
Parathyroid Hormone
Accelerates removal of calcium from bone to increase Ca levels in blood
PTH receptors present on both osteoblasts and osteoclasts
Osteoblasts respond to PTH by Change of shape and cytoskeletal arrangement Inhibition of collagen synthesis Stimulation of IL-6 macrophage colony-stimulating factor
secretion Chronic stimulation of the PTH causes hypocalcemia
and leads to resorptive effects of PTH on bone
Calcitonin
C cells of thyroid gland secrete calcitoninStraight chain peptide - 32 aaSynthesized from a large preprohormoneRise in plasma calcium is major stimulus
of calcitonin secretionPlasma concentration is 10-20 pgml and
half life is 5 min
Actions of Calcitonin
Osteoclasts are target cells for calcitoninMajor effect of clacitonin is rapid fall of
plasma calcium concentration caused by inhibition of bone resorption
Magnitude of decrease is proportional to the baseline rate of bone turnover
Other systemic hormones
Estrogens Increase bone remodeling
Androgens Increase bone formation
Other systemic hormones
Growth hormone Increases bone remodeling
Glucocorticoids Inhibit bone formation
Thyroid hormones Increase bone resorption Increase bone formation
Local regulators of bone remodeling
Cytokines IL-6 IL-1
ProstaglandinsGrowth factors
IGF-ITGF-β
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Osteocytes
Trapped osteoblasts1048708 In lacunae
Keep bone matrix in good condition and can release calcium ions from bone matrix when calcium demands increase1048708 Osteocytic osteolysis
Osteoblasts
Make collagenActivate nucleation of hydroxyapatite
crystallization onto the collagen matrix forming new bone
As they become enveloped by the collagenous matrix they produce they transform into osteocytes
Stimulate osteoclast resorptive activity
Osteoclasts
Resorbe bone matrix from sites where it is deteriorating or not needed
Digest bone matrix componentsFocal decalcification and extracellular
digestion by acid hydrolases and uptake of digested material
Disappear after resorptionAssist with mineral homeostasis
Chemistry of the bone
Matrix Mineral
Matrix - osteoid
Collagen type I and IVLayers of various orientations (add to the
strength of the matrix)Other proteins 10 of the bone protein
1048708 Direct formation of fibers1048708 Enhance mineralization1048708 Provide signals for remodeling
Mineral
A calcium phosphatecarbonate compound resembling the mineral hydroxyapatite Ca10(PO4)6(OH)2
1048708 Hydroxyapatite crystals1048708 Imperfect1048708 Contain Mg Na K
Mineralization of the bone
Calcification occurs by extracellular deposition of hydroxyapatite crystalsTrapping of calcium and phosphate ions in
concentrations that would initiate deposition of calcium phosphate in the solid phase followed by its conversion to crystalline hydroxyapatite
Mechanisms exist to both initiate and inhibit calcification
Bone remodeling process
Proceeds in cycles ndash first resorption than bone formation
The calcium content of bone turns over with a half-life of 1-5 years
Bone remodeling process
Coordination of Resorption and Formation
Phase ISignal from osteoblastsStimulation of osteoblastic precursor cells to
become osteoclastsProcess takes 10 days
Coordination of Resorption and Formation
Phase IIOsteoclast resorb bone creating cavity1048708 Macrophages clean up
Phase III1048708 New bone laid down by osteoblasts1048708 Takes 3 months
Pathways of differentiation ofosteoclasts and osteoblasts
Hormonal Influence
Vitamin DParathyroid HormoneCalcitoninEstrogenAndrogen
Vitamin D
Osteoblast have receptors for (125-(OH)2-D) Increases activity of both osteoblasts and
osteoclasts Increases osteocytic osteolysis (remodeling) Increases mineralization through increased
intestinal calcium absorption Feedback action of (125-(OH)2-D) represses
gene for PTH synthesis
Parathyroid Hormone
Accelerates removal of calcium from bone to increase Ca levels in blood
PTH receptors present on both osteoblasts and osteoclasts
Osteoblasts respond to PTH by Change of shape and cytoskeletal arrangement Inhibition of collagen synthesis Stimulation of IL-6 macrophage colony-stimulating factor
secretion Chronic stimulation of the PTH causes hypocalcemia
and leads to resorptive effects of PTH on bone
Calcitonin
C cells of thyroid gland secrete calcitoninStraight chain peptide - 32 aaSynthesized from a large preprohormoneRise in plasma calcium is major stimulus
of calcitonin secretionPlasma concentration is 10-20 pgml and
half life is 5 min
Actions of Calcitonin
Osteoclasts are target cells for calcitoninMajor effect of clacitonin is rapid fall of
plasma calcium concentration caused by inhibition of bone resorption
Magnitude of decrease is proportional to the baseline rate of bone turnover
Other systemic hormones
Estrogens Increase bone remodeling
Androgens Increase bone formation
Other systemic hormones
Growth hormone Increases bone remodeling
Glucocorticoids Inhibit bone formation
Thyroid hormones Increase bone resorption Increase bone formation
Local regulators of bone remodeling
Cytokines IL-6 IL-1
ProstaglandinsGrowth factors
IGF-ITGF-β
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Osteoblasts
Make collagenActivate nucleation of hydroxyapatite
crystallization onto the collagen matrix forming new bone
As they become enveloped by the collagenous matrix they produce they transform into osteocytes
Stimulate osteoclast resorptive activity
Osteoclasts
Resorbe bone matrix from sites where it is deteriorating or not needed
Digest bone matrix componentsFocal decalcification and extracellular
digestion by acid hydrolases and uptake of digested material
Disappear after resorptionAssist with mineral homeostasis
Chemistry of the bone
Matrix Mineral
Matrix - osteoid
Collagen type I and IVLayers of various orientations (add to the
strength of the matrix)Other proteins 10 of the bone protein
1048708 Direct formation of fibers1048708 Enhance mineralization1048708 Provide signals for remodeling
Mineral
A calcium phosphatecarbonate compound resembling the mineral hydroxyapatite Ca10(PO4)6(OH)2
1048708 Hydroxyapatite crystals1048708 Imperfect1048708 Contain Mg Na K
Mineralization of the bone
Calcification occurs by extracellular deposition of hydroxyapatite crystalsTrapping of calcium and phosphate ions in
concentrations that would initiate deposition of calcium phosphate in the solid phase followed by its conversion to crystalline hydroxyapatite
Mechanisms exist to both initiate and inhibit calcification
Bone remodeling process
Proceeds in cycles ndash first resorption than bone formation
The calcium content of bone turns over with a half-life of 1-5 years
Bone remodeling process
Coordination of Resorption and Formation
Phase ISignal from osteoblastsStimulation of osteoblastic precursor cells to
become osteoclastsProcess takes 10 days
Coordination of Resorption and Formation
Phase IIOsteoclast resorb bone creating cavity1048708 Macrophages clean up
Phase III1048708 New bone laid down by osteoblasts1048708 Takes 3 months
Pathways of differentiation ofosteoclasts and osteoblasts
Hormonal Influence
Vitamin DParathyroid HormoneCalcitoninEstrogenAndrogen
Vitamin D
Osteoblast have receptors for (125-(OH)2-D) Increases activity of both osteoblasts and
osteoclasts Increases osteocytic osteolysis (remodeling) Increases mineralization through increased
intestinal calcium absorption Feedback action of (125-(OH)2-D) represses
gene for PTH synthesis
Parathyroid Hormone
Accelerates removal of calcium from bone to increase Ca levels in blood
PTH receptors present on both osteoblasts and osteoclasts
Osteoblasts respond to PTH by Change of shape and cytoskeletal arrangement Inhibition of collagen synthesis Stimulation of IL-6 macrophage colony-stimulating factor
secretion Chronic stimulation of the PTH causes hypocalcemia
and leads to resorptive effects of PTH on bone
Calcitonin
C cells of thyroid gland secrete calcitoninStraight chain peptide - 32 aaSynthesized from a large preprohormoneRise in plasma calcium is major stimulus
of calcitonin secretionPlasma concentration is 10-20 pgml and
half life is 5 min
Actions of Calcitonin
Osteoclasts are target cells for calcitoninMajor effect of clacitonin is rapid fall of
plasma calcium concentration caused by inhibition of bone resorption
Magnitude of decrease is proportional to the baseline rate of bone turnover
Other systemic hormones
Estrogens Increase bone remodeling
Androgens Increase bone formation
Other systemic hormones
Growth hormone Increases bone remodeling
Glucocorticoids Inhibit bone formation
Thyroid hormones Increase bone resorption Increase bone formation
Local regulators of bone remodeling
Cytokines IL-6 IL-1
ProstaglandinsGrowth factors
IGF-ITGF-β
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Osteoclasts
Resorbe bone matrix from sites where it is deteriorating or not needed
Digest bone matrix componentsFocal decalcification and extracellular
digestion by acid hydrolases and uptake of digested material
Disappear after resorptionAssist with mineral homeostasis
Chemistry of the bone
Matrix Mineral
Matrix - osteoid
Collagen type I and IVLayers of various orientations (add to the
strength of the matrix)Other proteins 10 of the bone protein
1048708 Direct formation of fibers1048708 Enhance mineralization1048708 Provide signals for remodeling
Mineral
A calcium phosphatecarbonate compound resembling the mineral hydroxyapatite Ca10(PO4)6(OH)2
1048708 Hydroxyapatite crystals1048708 Imperfect1048708 Contain Mg Na K
Mineralization of the bone
Calcification occurs by extracellular deposition of hydroxyapatite crystalsTrapping of calcium and phosphate ions in
concentrations that would initiate deposition of calcium phosphate in the solid phase followed by its conversion to crystalline hydroxyapatite
Mechanisms exist to both initiate and inhibit calcification
Bone remodeling process
Proceeds in cycles ndash first resorption than bone formation
The calcium content of bone turns over with a half-life of 1-5 years
Bone remodeling process
Coordination of Resorption and Formation
Phase ISignal from osteoblastsStimulation of osteoblastic precursor cells to
become osteoclastsProcess takes 10 days
Coordination of Resorption and Formation
Phase IIOsteoclast resorb bone creating cavity1048708 Macrophages clean up
Phase III1048708 New bone laid down by osteoblasts1048708 Takes 3 months
Pathways of differentiation ofosteoclasts and osteoblasts
Hormonal Influence
Vitamin DParathyroid HormoneCalcitoninEstrogenAndrogen
Vitamin D
Osteoblast have receptors for (125-(OH)2-D) Increases activity of both osteoblasts and
osteoclasts Increases osteocytic osteolysis (remodeling) Increases mineralization through increased
intestinal calcium absorption Feedback action of (125-(OH)2-D) represses
gene for PTH synthesis
Parathyroid Hormone
Accelerates removal of calcium from bone to increase Ca levels in blood
PTH receptors present on both osteoblasts and osteoclasts
Osteoblasts respond to PTH by Change of shape and cytoskeletal arrangement Inhibition of collagen synthesis Stimulation of IL-6 macrophage colony-stimulating factor
secretion Chronic stimulation of the PTH causes hypocalcemia
and leads to resorptive effects of PTH on bone
Calcitonin
C cells of thyroid gland secrete calcitoninStraight chain peptide - 32 aaSynthesized from a large preprohormoneRise in plasma calcium is major stimulus
of calcitonin secretionPlasma concentration is 10-20 pgml and
half life is 5 min
Actions of Calcitonin
Osteoclasts are target cells for calcitoninMajor effect of clacitonin is rapid fall of
plasma calcium concentration caused by inhibition of bone resorption
Magnitude of decrease is proportional to the baseline rate of bone turnover
Other systemic hormones
Estrogens Increase bone remodeling
Androgens Increase bone formation
Other systemic hormones
Growth hormone Increases bone remodeling
Glucocorticoids Inhibit bone formation
Thyroid hormones Increase bone resorption Increase bone formation
Local regulators of bone remodeling
Cytokines IL-6 IL-1
ProstaglandinsGrowth factors
IGF-ITGF-β
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Chemistry of the bone
Matrix Mineral
Matrix - osteoid
Collagen type I and IVLayers of various orientations (add to the
strength of the matrix)Other proteins 10 of the bone protein
1048708 Direct formation of fibers1048708 Enhance mineralization1048708 Provide signals for remodeling
Mineral
A calcium phosphatecarbonate compound resembling the mineral hydroxyapatite Ca10(PO4)6(OH)2
1048708 Hydroxyapatite crystals1048708 Imperfect1048708 Contain Mg Na K
Mineralization of the bone
Calcification occurs by extracellular deposition of hydroxyapatite crystalsTrapping of calcium and phosphate ions in
concentrations that would initiate deposition of calcium phosphate in the solid phase followed by its conversion to crystalline hydroxyapatite
Mechanisms exist to both initiate and inhibit calcification
Bone remodeling process
Proceeds in cycles ndash first resorption than bone formation
The calcium content of bone turns over with a half-life of 1-5 years
Bone remodeling process
Coordination of Resorption and Formation
Phase ISignal from osteoblastsStimulation of osteoblastic precursor cells to
become osteoclastsProcess takes 10 days
Coordination of Resorption and Formation
Phase IIOsteoclast resorb bone creating cavity1048708 Macrophages clean up
Phase III1048708 New bone laid down by osteoblasts1048708 Takes 3 months
Pathways of differentiation ofosteoclasts and osteoblasts
Hormonal Influence
Vitamin DParathyroid HormoneCalcitoninEstrogenAndrogen
Vitamin D
Osteoblast have receptors for (125-(OH)2-D) Increases activity of both osteoblasts and
osteoclasts Increases osteocytic osteolysis (remodeling) Increases mineralization through increased
intestinal calcium absorption Feedback action of (125-(OH)2-D) represses
gene for PTH synthesis
Parathyroid Hormone
Accelerates removal of calcium from bone to increase Ca levels in blood
PTH receptors present on both osteoblasts and osteoclasts
Osteoblasts respond to PTH by Change of shape and cytoskeletal arrangement Inhibition of collagen synthesis Stimulation of IL-6 macrophage colony-stimulating factor
secretion Chronic stimulation of the PTH causes hypocalcemia
and leads to resorptive effects of PTH on bone
Calcitonin
C cells of thyroid gland secrete calcitoninStraight chain peptide - 32 aaSynthesized from a large preprohormoneRise in plasma calcium is major stimulus
of calcitonin secretionPlasma concentration is 10-20 pgml and
half life is 5 min
Actions of Calcitonin
Osteoclasts are target cells for calcitoninMajor effect of clacitonin is rapid fall of
plasma calcium concentration caused by inhibition of bone resorption
Magnitude of decrease is proportional to the baseline rate of bone turnover
Other systemic hormones
Estrogens Increase bone remodeling
Androgens Increase bone formation
Other systemic hormones
Growth hormone Increases bone remodeling
Glucocorticoids Inhibit bone formation
Thyroid hormones Increase bone resorption Increase bone formation
Local regulators of bone remodeling
Cytokines IL-6 IL-1
ProstaglandinsGrowth factors
IGF-ITGF-β
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Matrix - osteoid
Collagen type I and IVLayers of various orientations (add to the
strength of the matrix)Other proteins 10 of the bone protein
1048708 Direct formation of fibers1048708 Enhance mineralization1048708 Provide signals for remodeling
Mineral
A calcium phosphatecarbonate compound resembling the mineral hydroxyapatite Ca10(PO4)6(OH)2
1048708 Hydroxyapatite crystals1048708 Imperfect1048708 Contain Mg Na K
Mineralization of the bone
Calcification occurs by extracellular deposition of hydroxyapatite crystalsTrapping of calcium and phosphate ions in
concentrations that would initiate deposition of calcium phosphate in the solid phase followed by its conversion to crystalline hydroxyapatite
Mechanisms exist to both initiate and inhibit calcification
Bone remodeling process
Proceeds in cycles ndash first resorption than bone formation
The calcium content of bone turns over with a half-life of 1-5 years
Bone remodeling process
Coordination of Resorption and Formation
Phase ISignal from osteoblastsStimulation of osteoblastic precursor cells to
become osteoclastsProcess takes 10 days
Coordination of Resorption and Formation
Phase IIOsteoclast resorb bone creating cavity1048708 Macrophages clean up
Phase III1048708 New bone laid down by osteoblasts1048708 Takes 3 months
Pathways of differentiation ofosteoclasts and osteoblasts
Hormonal Influence
Vitamin DParathyroid HormoneCalcitoninEstrogenAndrogen
Vitamin D
Osteoblast have receptors for (125-(OH)2-D) Increases activity of both osteoblasts and
osteoclasts Increases osteocytic osteolysis (remodeling) Increases mineralization through increased
intestinal calcium absorption Feedback action of (125-(OH)2-D) represses
gene for PTH synthesis
Parathyroid Hormone
Accelerates removal of calcium from bone to increase Ca levels in blood
PTH receptors present on both osteoblasts and osteoclasts
Osteoblasts respond to PTH by Change of shape and cytoskeletal arrangement Inhibition of collagen synthesis Stimulation of IL-6 macrophage colony-stimulating factor
secretion Chronic stimulation of the PTH causes hypocalcemia
and leads to resorptive effects of PTH on bone
Calcitonin
C cells of thyroid gland secrete calcitoninStraight chain peptide - 32 aaSynthesized from a large preprohormoneRise in plasma calcium is major stimulus
of calcitonin secretionPlasma concentration is 10-20 pgml and
half life is 5 min
Actions of Calcitonin
Osteoclasts are target cells for calcitoninMajor effect of clacitonin is rapid fall of
plasma calcium concentration caused by inhibition of bone resorption
Magnitude of decrease is proportional to the baseline rate of bone turnover
Other systemic hormones
Estrogens Increase bone remodeling
Androgens Increase bone formation
Other systemic hormones
Growth hormone Increases bone remodeling
Glucocorticoids Inhibit bone formation
Thyroid hormones Increase bone resorption Increase bone formation
Local regulators of bone remodeling
Cytokines IL-6 IL-1
ProstaglandinsGrowth factors
IGF-ITGF-β
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Mineral
A calcium phosphatecarbonate compound resembling the mineral hydroxyapatite Ca10(PO4)6(OH)2
1048708 Hydroxyapatite crystals1048708 Imperfect1048708 Contain Mg Na K
Mineralization of the bone
Calcification occurs by extracellular deposition of hydroxyapatite crystalsTrapping of calcium and phosphate ions in
concentrations that would initiate deposition of calcium phosphate in the solid phase followed by its conversion to crystalline hydroxyapatite
Mechanisms exist to both initiate and inhibit calcification
Bone remodeling process
Proceeds in cycles ndash first resorption than bone formation
The calcium content of bone turns over with a half-life of 1-5 years
Bone remodeling process
Coordination of Resorption and Formation
Phase ISignal from osteoblastsStimulation of osteoblastic precursor cells to
become osteoclastsProcess takes 10 days
Coordination of Resorption and Formation
Phase IIOsteoclast resorb bone creating cavity1048708 Macrophages clean up
Phase III1048708 New bone laid down by osteoblasts1048708 Takes 3 months
Pathways of differentiation ofosteoclasts and osteoblasts
Hormonal Influence
Vitamin DParathyroid HormoneCalcitoninEstrogenAndrogen
Vitamin D
Osteoblast have receptors for (125-(OH)2-D) Increases activity of both osteoblasts and
osteoclasts Increases osteocytic osteolysis (remodeling) Increases mineralization through increased
intestinal calcium absorption Feedback action of (125-(OH)2-D) represses
gene for PTH synthesis
Parathyroid Hormone
Accelerates removal of calcium from bone to increase Ca levels in blood
PTH receptors present on both osteoblasts and osteoclasts
Osteoblasts respond to PTH by Change of shape and cytoskeletal arrangement Inhibition of collagen synthesis Stimulation of IL-6 macrophage colony-stimulating factor
secretion Chronic stimulation of the PTH causes hypocalcemia
and leads to resorptive effects of PTH on bone
Calcitonin
C cells of thyroid gland secrete calcitoninStraight chain peptide - 32 aaSynthesized from a large preprohormoneRise in plasma calcium is major stimulus
of calcitonin secretionPlasma concentration is 10-20 pgml and
half life is 5 min
Actions of Calcitonin
Osteoclasts are target cells for calcitoninMajor effect of clacitonin is rapid fall of
plasma calcium concentration caused by inhibition of bone resorption
Magnitude of decrease is proportional to the baseline rate of bone turnover
Other systemic hormones
Estrogens Increase bone remodeling
Androgens Increase bone formation
Other systemic hormones
Growth hormone Increases bone remodeling
Glucocorticoids Inhibit bone formation
Thyroid hormones Increase bone resorption Increase bone formation
Local regulators of bone remodeling
Cytokines IL-6 IL-1
ProstaglandinsGrowth factors
IGF-ITGF-β
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Mineralization of the bone
Calcification occurs by extracellular deposition of hydroxyapatite crystalsTrapping of calcium and phosphate ions in
concentrations that would initiate deposition of calcium phosphate in the solid phase followed by its conversion to crystalline hydroxyapatite
Mechanisms exist to both initiate and inhibit calcification
Bone remodeling process
Proceeds in cycles ndash first resorption than bone formation
The calcium content of bone turns over with a half-life of 1-5 years
Bone remodeling process
Coordination of Resorption and Formation
Phase ISignal from osteoblastsStimulation of osteoblastic precursor cells to
become osteoclastsProcess takes 10 days
Coordination of Resorption and Formation
Phase IIOsteoclast resorb bone creating cavity1048708 Macrophages clean up
Phase III1048708 New bone laid down by osteoblasts1048708 Takes 3 months
Pathways of differentiation ofosteoclasts and osteoblasts
Hormonal Influence
Vitamin DParathyroid HormoneCalcitoninEstrogenAndrogen
Vitamin D
Osteoblast have receptors for (125-(OH)2-D) Increases activity of both osteoblasts and
osteoclasts Increases osteocytic osteolysis (remodeling) Increases mineralization through increased
intestinal calcium absorption Feedback action of (125-(OH)2-D) represses
gene for PTH synthesis
Parathyroid Hormone
Accelerates removal of calcium from bone to increase Ca levels in blood
PTH receptors present on both osteoblasts and osteoclasts
Osteoblasts respond to PTH by Change of shape and cytoskeletal arrangement Inhibition of collagen synthesis Stimulation of IL-6 macrophage colony-stimulating factor
secretion Chronic stimulation of the PTH causes hypocalcemia
and leads to resorptive effects of PTH on bone
Calcitonin
C cells of thyroid gland secrete calcitoninStraight chain peptide - 32 aaSynthesized from a large preprohormoneRise in plasma calcium is major stimulus
of calcitonin secretionPlasma concentration is 10-20 pgml and
half life is 5 min
Actions of Calcitonin
Osteoclasts are target cells for calcitoninMajor effect of clacitonin is rapid fall of
plasma calcium concentration caused by inhibition of bone resorption
Magnitude of decrease is proportional to the baseline rate of bone turnover
Other systemic hormones
Estrogens Increase bone remodeling
Androgens Increase bone formation
Other systemic hormones
Growth hormone Increases bone remodeling
Glucocorticoids Inhibit bone formation
Thyroid hormones Increase bone resorption Increase bone formation
Local regulators of bone remodeling
Cytokines IL-6 IL-1
ProstaglandinsGrowth factors
IGF-ITGF-β
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Bone remodeling process
Proceeds in cycles ndash first resorption than bone formation
The calcium content of bone turns over with a half-life of 1-5 years
Bone remodeling process
Coordination of Resorption and Formation
Phase ISignal from osteoblastsStimulation of osteoblastic precursor cells to
become osteoclastsProcess takes 10 days
Coordination of Resorption and Formation
Phase IIOsteoclast resorb bone creating cavity1048708 Macrophages clean up
Phase III1048708 New bone laid down by osteoblasts1048708 Takes 3 months
Pathways of differentiation ofosteoclasts and osteoblasts
Hormonal Influence
Vitamin DParathyroid HormoneCalcitoninEstrogenAndrogen
Vitamin D
Osteoblast have receptors for (125-(OH)2-D) Increases activity of both osteoblasts and
osteoclasts Increases osteocytic osteolysis (remodeling) Increases mineralization through increased
intestinal calcium absorption Feedback action of (125-(OH)2-D) represses
gene for PTH synthesis
Parathyroid Hormone
Accelerates removal of calcium from bone to increase Ca levels in blood
PTH receptors present on both osteoblasts and osteoclasts
Osteoblasts respond to PTH by Change of shape and cytoskeletal arrangement Inhibition of collagen synthesis Stimulation of IL-6 macrophage colony-stimulating factor
secretion Chronic stimulation of the PTH causes hypocalcemia
and leads to resorptive effects of PTH on bone
Calcitonin
C cells of thyroid gland secrete calcitoninStraight chain peptide - 32 aaSynthesized from a large preprohormoneRise in plasma calcium is major stimulus
of calcitonin secretionPlasma concentration is 10-20 pgml and
half life is 5 min
Actions of Calcitonin
Osteoclasts are target cells for calcitoninMajor effect of clacitonin is rapid fall of
plasma calcium concentration caused by inhibition of bone resorption
Magnitude of decrease is proportional to the baseline rate of bone turnover
Other systemic hormones
Estrogens Increase bone remodeling
Androgens Increase bone formation
Other systemic hormones
Growth hormone Increases bone remodeling
Glucocorticoids Inhibit bone formation
Thyroid hormones Increase bone resorption Increase bone formation
Local regulators of bone remodeling
Cytokines IL-6 IL-1
ProstaglandinsGrowth factors
IGF-ITGF-β
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Bone remodeling process
Coordination of Resorption and Formation
Phase ISignal from osteoblastsStimulation of osteoblastic precursor cells to
become osteoclastsProcess takes 10 days
Coordination of Resorption and Formation
Phase IIOsteoclast resorb bone creating cavity1048708 Macrophages clean up
Phase III1048708 New bone laid down by osteoblasts1048708 Takes 3 months
Pathways of differentiation ofosteoclasts and osteoblasts
Hormonal Influence
Vitamin DParathyroid HormoneCalcitoninEstrogenAndrogen
Vitamin D
Osteoblast have receptors for (125-(OH)2-D) Increases activity of both osteoblasts and
osteoclasts Increases osteocytic osteolysis (remodeling) Increases mineralization through increased
intestinal calcium absorption Feedback action of (125-(OH)2-D) represses
gene for PTH synthesis
Parathyroid Hormone
Accelerates removal of calcium from bone to increase Ca levels in blood
PTH receptors present on both osteoblasts and osteoclasts
Osteoblasts respond to PTH by Change of shape and cytoskeletal arrangement Inhibition of collagen synthesis Stimulation of IL-6 macrophage colony-stimulating factor
secretion Chronic stimulation of the PTH causes hypocalcemia
and leads to resorptive effects of PTH on bone
Calcitonin
C cells of thyroid gland secrete calcitoninStraight chain peptide - 32 aaSynthesized from a large preprohormoneRise in plasma calcium is major stimulus
of calcitonin secretionPlasma concentration is 10-20 pgml and
half life is 5 min
Actions of Calcitonin
Osteoclasts are target cells for calcitoninMajor effect of clacitonin is rapid fall of
plasma calcium concentration caused by inhibition of bone resorption
Magnitude of decrease is proportional to the baseline rate of bone turnover
Other systemic hormones
Estrogens Increase bone remodeling
Androgens Increase bone formation
Other systemic hormones
Growth hormone Increases bone remodeling
Glucocorticoids Inhibit bone formation
Thyroid hormones Increase bone resorption Increase bone formation
Local regulators of bone remodeling
Cytokines IL-6 IL-1
ProstaglandinsGrowth factors
IGF-ITGF-β
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Coordination of Resorption and Formation
Phase ISignal from osteoblastsStimulation of osteoblastic precursor cells to
become osteoclastsProcess takes 10 days
Coordination of Resorption and Formation
Phase IIOsteoclast resorb bone creating cavity1048708 Macrophages clean up
Phase III1048708 New bone laid down by osteoblasts1048708 Takes 3 months
Pathways of differentiation ofosteoclasts and osteoblasts
Hormonal Influence
Vitamin DParathyroid HormoneCalcitoninEstrogenAndrogen
Vitamin D
Osteoblast have receptors for (125-(OH)2-D) Increases activity of both osteoblasts and
osteoclasts Increases osteocytic osteolysis (remodeling) Increases mineralization through increased
intestinal calcium absorption Feedback action of (125-(OH)2-D) represses
gene for PTH synthesis
Parathyroid Hormone
Accelerates removal of calcium from bone to increase Ca levels in blood
PTH receptors present on both osteoblasts and osteoclasts
Osteoblasts respond to PTH by Change of shape and cytoskeletal arrangement Inhibition of collagen synthesis Stimulation of IL-6 macrophage colony-stimulating factor
secretion Chronic stimulation of the PTH causes hypocalcemia
and leads to resorptive effects of PTH on bone
Calcitonin
C cells of thyroid gland secrete calcitoninStraight chain peptide - 32 aaSynthesized from a large preprohormoneRise in plasma calcium is major stimulus
of calcitonin secretionPlasma concentration is 10-20 pgml and
half life is 5 min
Actions of Calcitonin
Osteoclasts are target cells for calcitoninMajor effect of clacitonin is rapid fall of
plasma calcium concentration caused by inhibition of bone resorption
Magnitude of decrease is proportional to the baseline rate of bone turnover
Other systemic hormones
Estrogens Increase bone remodeling
Androgens Increase bone formation
Other systemic hormones
Growth hormone Increases bone remodeling
Glucocorticoids Inhibit bone formation
Thyroid hormones Increase bone resorption Increase bone formation
Local regulators of bone remodeling
Cytokines IL-6 IL-1
ProstaglandinsGrowth factors
IGF-ITGF-β
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Coordination of Resorption and Formation
Phase IIOsteoclast resorb bone creating cavity1048708 Macrophages clean up
Phase III1048708 New bone laid down by osteoblasts1048708 Takes 3 months
Pathways of differentiation ofosteoclasts and osteoblasts
Hormonal Influence
Vitamin DParathyroid HormoneCalcitoninEstrogenAndrogen
Vitamin D
Osteoblast have receptors for (125-(OH)2-D) Increases activity of both osteoblasts and
osteoclasts Increases osteocytic osteolysis (remodeling) Increases mineralization through increased
intestinal calcium absorption Feedback action of (125-(OH)2-D) represses
gene for PTH synthesis
Parathyroid Hormone
Accelerates removal of calcium from bone to increase Ca levels in blood
PTH receptors present on both osteoblasts and osteoclasts
Osteoblasts respond to PTH by Change of shape and cytoskeletal arrangement Inhibition of collagen synthesis Stimulation of IL-6 macrophage colony-stimulating factor
secretion Chronic stimulation of the PTH causes hypocalcemia
and leads to resorptive effects of PTH on bone
Calcitonin
C cells of thyroid gland secrete calcitoninStraight chain peptide - 32 aaSynthesized from a large preprohormoneRise in plasma calcium is major stimulus
of calcitonin secretionPlasma concentration is 10-20 pgml and
half life is 5 min
Actions of Calcitonin
Osteoclasts are target cells for calcitoninMajor effect of clacitonin is rapid fall of
plasma calcium concentration caused by inhibition of bone resorption
Magnitude of decrease is proportional to the baseline rate of bone turnover
Other systemic hormones
Estrogens Increase bone remodeling
Androgens Increase bone formation
Other systemic hormones
Growth hormone Increases bone remodeling
Glucocorticoids Inhibit bone formation
Thyroid hormones Increase bone resorption Increase bone formation
Local regulators of bone remodeling
Cytokines IL-6 IL-1
ProstaglandinsGrowth factors
IGF-ITGF-β
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Pathways of differentiation ofosteoclasts and osteoblasts
Hormonal Influence
Vitamin DParathyroid HormoneCalcitoninEstrogenAndrogen
Vitamin D
Osteoblast have receptors for (125-(OH)2-D) Increases activity of both osteoblasts and
osteoclasts Increases osteocytic osteolysis (remodeling) Increases mineralization through increased
intestinal calcium absorption Feedback action of (125-(OH)2-D) represses
gene for PTH synthesis
Parathyroid Hormone
Accelerates removal of calcium from bone to increase Ca levels in blood
PTH receptors present on both osteoblasts and osteoclasts
Osteoblasts respond to PTH by Change of shape and cytoskeletal arrangement Inhibition of collagen synthesis Stimulation of IL-6 macrophage colony-stimulating factor
secretion Chronic stimulation of the PTH causes hypocalcemia
and leads to resorptive effects of PTH on bone
Calcitonin
C cells of thyroid gland secrete calcitoninStraight chain peptide - 32 aaSynthesized from a large preprohormoneRise in plasma calcium is major stimulus
of calcitonin secretionPlasma concentration is 10-20 pgml and
half life is 5 min
Actions of Calcitonin
Osteoclasts are target cells for calcitoninMajor effect of clacitonin is rapid fall of
plasma calcium concentration caused by inhibition of bone resorption
Magnitude of decrease is proportional to the baseline rate of bone turnover
Other systemic hormones
Estrogens Increase bone remodeling
Androgens Increase bone formation
Other systemic hormones
Growth hormone Increases bone remodeling
Glucocorticoids Inhibit bone formation
Thyroid hormones Increase bone resorption Increase bone formation
Local regulators of bone remodeling
Cytokines IL-6 IL-1
ProstaglandinsGrowth factors
IGF-ITGF-β
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Hormonal Influence
Vitamin DParathyroid HormoneCalcitoninEstrogenAndrogen
Vitamin D
Osteoblast have receptors for (125-(OH)2-D) Increases activity of both osteoblasts and
osteoclasts Increases osteocytic osteolysis (remodeling) Increases mineralization through increased
intestinal calcium absorption Feedback action of (125-(OH)2-D) represses
gene for PTH synthesis
Parathyroid Hormone
Accelerates removal of calcium from bone to increase Ca levels in blood
PTH receptors present on both osteoblasts and osteoclasts
Osteoblasts respond to PTH by Change of shape and cytoskeletal arrangement Inhibition of collagen synthesis Stimulation of IL-6 macrophage colony-stimulating factor
secretion Chronic stimulation of the PTH causes hypocalcemia
and leads to resorptive effects of PTH on bone
Calcitonin
C cells of thyroid gland secrete calcitoninStraight chain peptide - 32 aaSynthesized from a large preprohormoneRise in plasma calcium is major stimulus
of calcitonin secretionPlasma concentration is 10-20 pgml and
half life is 5 min
Actions of Calcitonin
Osteoclasts are target cells for calcitoninMajor effect of clacitonin is rapid fall of
plasma calcium concentration caused by inhibition of bone resorption
Magnitude of decrease is proportional to the baseline rate of bone turnover
Other systemic hormones
Estrogens Increase bone remodeling
Androgens Increase bone formation
Other systemic hormones
Growth hormone Increases bone remodeling
Glucocorticoids Inhibit bone formation
Thyroid hormones Increase bone resorption Increase bone formation
Local regulators of bone remodeling
Cytokines IL-6 IL-1
ProstaglandinsGrowth factors
IGF-ITGF-β
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Vitamin D
Osteoblast have receptors for (125-(OH)2-D) Increases activity of both osteoblasts and
osteoclasts Increases osteocytic osteolysis (remodeling) Increases mineralization through increased
intestinal calcium absorption Feedback action of (125-(OH)2-D) represses
gene for PTH synthesis
Parathyroid Hormone
Accelerates removal of calcium from bone to increase Ca levels in blood
PTH receptors present on both osteoblasts and osteoclasts
Osteoblasts respond to PTH by Change of shape and cytoskeletal arrangement Inhibition of collagen synthesis Stimulation of IL-6 macrophage colony-stimulating factor
secretion Chronic stimulation of the PTH causes hypocalcemia
and leads to resorptive effects of PTH on bone
Calcitonin
C cells of thyroid gland secrete calcitoninStraight chain peptide - 32 aaSynthesized from a large preprohormoneRise in plasma calcium is major stimulus
of calcitonin secretionPlasma concentration is 10-20 pgml and
half life is 5 min
Actions of Calcitonin
Osteoclasts are target cells for calcitoninMajor effect of clacitonin is rapid fall of
plasma calcium concentration caused by inhibition of bone resorption
Magnitude of decrease is proportional to the baseline rate of bone turnover
Other systemic hormones
Estrogens Increase bone remodeling
Androgens Increase bone formation
Other systemic hormones
Growth hormone Increases bone remodeling
Glucocorticoids Inhibit bone formation
Thyroid hormones Increase bone resorption Increase bone formation
Local regulators of bone remodeling
Cytokines IL-6 IL-1
ProstaglandinsGrowth factors
IGF-ITGF-β
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Parathyroid Hormone
Accelerates removal of calcium from bone to increase Ca levels in blood
PTH receptors present on both osteoblasts and osteoclasts
Osteoblasts respond to PTH by Change of shape and cytoskeletal arrangement Inhibition of collagen synthesis Stimulation of IL-6 macrophage colony-stimulating factor
secretion Chronic stimulation of the PTH causes hypocalcemia
and leads to resorptive effects of PTH on bone
Calcitonin
C cells of thyroid gland secrete calcitoninStraight chain peptide - 32 aaSynthesized from a large preprohormoneRise in plasma calcium is major stimulus
of calcitonin secretionPlasma concentration is 10-20 pgml and
half life is 5 min
Actions of Calcitonin
Osteoclasts are target cells for calcitoninMajor effect of clacitonin is rapid fall of
plasma calcium concentration caused by inhibition of bone resorption
Magnitude of decrease is proportional to the baseline rate of bone turnover
Other systemic hormones
Estrogens Increase bone remodeling
Androgens Increase bone formation
Other systemic hormones
Growth hormone Increases bone remodeling
Glucocorticoids Inhibit bone formation
Thyroid hormones Increase bone resorption Increase bone formation
Local regulators of bone remodeling
Cytokines IL-6 IL-1
ProstaglandinsGrowth factors
IGF-ITGF-β
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Calcitonin
C cells of thyroid gland secrete calcitoninStraight chain peptide - 32 aaSynthesized from a large preprohormoneRise in plasma calcium is major stimulus
of calcitonin secretionPlasma concentration is 10-20 pgml and
half life is 5 min
Actions of Calcitonin
Osteoclasts are target cells for calcitoninMajor effect of clacitonin is rapid fall of
plasma calcium concentration caused by inhibition of bone resorption
Magnitude of decrease is proportional to the baseline rate of bone turnover
Other systemic hormones
Estrogens Increase bone remodeling
Androgens Increase bone formation
Other systemic hormones
Growth hormone Increases bone remodeling
Glucocorticoids Inhibit bone formation
Thyroid hormones Increase bone resorption Increase bone formation
Local regulators of bone remodeling
Cytokines IL-6 IL-1
ProstaglandinsGrowth factors
IGF-ITGF-β
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Actions of Calcitonin
Osteoclasts are target cells for calcitoninMajor effect of clacitonin is rapid fall of
plasma calcium concentration caused by inhibition of bone resorption
Magnitude of decrease is proportional to the baseline rate of bone turnover
Other systemic hormones
Estrogens Increase bone remodeling
Androgens Increase bone formation
Other systemic hormones
Growth hormone Increases bone remodeling
Glucocorticoids Inhibit bone formation
Thyroid hormones Increase bone resorption Increase bone formation
Local regulators of bone remodeling
Cytokines IL-6 IL-1
ProstaglandinsGrowth factors
IGF-ITGF-β
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Other systemic hormones
Estrogens Increase bone remodeling
Androgens Increase bone formation
Other systemic hormones
Growth hormone Increases bone remodeling
Glucocorticoids Inhibit bone formation
Thyroid hormones Increase bone resorption Increase bone formation
Local regulators of bone remodeling
Cytokines IL-6 IL-1
ProstaglandinsGrowth factors
IGF-ITGF-β
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Other systemic hormones
Growth hormone Increases bone remodeling
Glucocorticoids Inhibit bone formation
Thyroid hormones Increase bone resorption Increase bone formation
Local regulators of bone remodeling
Cytokines IL-6 IL-1
ProstaglandinsGrowth factors
IGF-ITGF-β
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Local regulators of bone remodeling
Cytokines IL-6 IL-1
ProstaglandinsGrowth factors
IGF-ITGF-β
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Osteoporosis
A disease characterized by low bone massmicroarchitectural deterioration of the bone
tissue
Leading toenhanced bone fragility increase in fracture risk
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
WHO guidelines for determiningosteoporosis
Normal Not less than 1 SD below the avg for young adults
Osteopenia -1 to -25 SD below the mean Osteoporosis More than 25 SD below the
young adult average 70 of women over 80 with no estrogen
replacement therapy qualify
Severe osteoporosis More than 25 SD below with fractures
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Osteoporosis - epidemiology
Disorder of postmenopausal women of northern European descent
Increase in the incidence related to decreasing physical activity
Over 27 million or 1of 3 women are affected with osteoporosis
Over 5 million or 1of 5 men are affected with osteoporosis
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Bone Mass
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Statistics
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Prevalence of Osteopenia and Osteoporosis in Postmenopausal Women by Ethnicity
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Pathogenesis of EstrogenDeficiency and Bone Loss
Estrogen loss triggers increases in IL-1 IL-6 and TNF due toReduced suppression of gene
transcription of IL-6 and TNF Increased number of monocytes Increased cytokines lead to increased
osteoclast development and lifespan
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Osteoclast Differentiation andActivation in Estrogen Deficiency
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Impact of Estrogen on Osteoclastic Differentiation and Activation
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
National Osteoporosis Risk Assessment (NORA) Factors Associated With Increased Risk of Osteoporosis
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
NORA Factors Associated With Reduced Risk of Osteoporosis
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
NORA BMD and Fracture Rate
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Osteoporosis
Mechanisms causing osteoporosis Imbalance between rate of resorption and
formationFailure to complete 3 stages of remodeling
Types of osteoporosisType IType IISecondary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Osteoporosis - types
Postmenopausal osteoporosis (type I)Caused by lack of estrogenCauses PTH to over stimulate osteoclastsExcessive loss of trabecular bone
Age-associated osteoporosis (type II)Bone loss due to increased bone turnoverMalabsorptionMineral and vitamin deficiency
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Secondary osteoporosis
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Osteoporotic vertebra
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Normal vs osteoporotic bone
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Risk Factors
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
When to Measure BMD inPostmenopausal Women
All women 65 years and olderPostmenopausal women lt65 years of
age If result might influence decisions about
interventionOne or more risk factorsHistory of fracture
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
When Measurement of BMD IsNot Appropriate
Healthy premenopausal womenHealthy children and adolescentsWomen initiating ETHT for
menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Prediction of Fracture Risk
All techniques (DXA QCT QUS) predict fracture risk
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Osteoporosis can be Assessed by DXA
Relative Risk of Fracture per SD Decrease in BMD
0
05
1
15
2
25
3
Forea
rm Hip
Verteb
ral
All Site
s
Rel
ativ
e R
isk
Forearm
Hip
Spine
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture riskPopulation surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites
Marshall D et al Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures British Medical Journal 3121254-1259 1996
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
The McCue CUBA Ultrasonometry Technology that can Assess Osteoporosis
OsteoporoticBoneFrequency
BUA110 NormaldBMHz
40dBMHz
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Heel BUA is Significantly Lower in Subjects With Future Hip Fracture
0
10
20
30
40
50
60
Fracture No Fracture
BU
A (
dB
sq
MH
z)
Subjects who developed hip fracture showed significantly (plt0001) lower heel BUA results in a two-year follow-up prospective study of 1414 subjects
Porter RW et al Prediction of hip fracture in elderly women a prospective study British Medical Journal 301638-641 1990
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Discriminating Power of Heel BUA in Reflecting Vertebral Osteoporosis
0
01
02
03
04
05
06
07
08
09
1
Heel BUA Spine BMD Neck BMD Trochanter BMD
Are
a U
nd
er
the C
urv
e
When assessing vertebral osteoporosis there was no statistically significant difference in the discriminating power of Heel BUA or Spine Femur Neck or Trochanter BMD by DXA
Ohishi T et al Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fracture Journal of Clinical Densitometry 3227-231 2000
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Receiver Operator Characteristic Analysis of Hip Fracture Risk
05
055
06
065
07
075
08
085
09
Heel BUA Femur Neck BMD
Are
a U
nd
er t
he
Cu
rve
Schott AM et al Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density
Journal of Bone and Mineral Research 10243-249 1995
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Increasing Relative Fracture Risk is Seen with Decreased BUA or BMD
0
05
1
15
2
25
3
Hans et al Bauer et al Frost et al
Research Study
Rel
ativ
e R
isk
of
Fra
ctu
re
BUA
BMD
Hans D et al Ultrasonographic heel measurements to predict hip fracture in elderly women the EPIDOS prospective study Lancet 348511-514 1996
Bauer DC et al Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women Archieves of Internal Medicine 157629-634 1997
Frost ML et al A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other than the spine and hip Calcified Tissue International 71207-211 2002
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Increased Relative Fracture Risk is Seen With Decreasing BUA
005
115
225
335
445
5
lt10 10 to lt40 40 to lt70 70 to 100
Percentile Category
Rel
ativ
e F
ract
ure
Ris
k
14824 men and women were followed for an average of 19 years to relate BUA to future fracture riskSubjects in the lowest 10th percentile of BUA showed a relative risk of fracture 444 times greater than those in the highest 30th percentile of BUA
Khaw KT et al Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus EPIC-Norfolk prospective study Lancet 363197-202 2004
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Who Should Be Consideredfor Prevention or Treatment
Postmenopausal women with T-score below ndash20 with no risk factors
Postmenopausal women with T-score below ndash15 with one or more risk factors
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
NORA
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
NORA
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Prevention of Bone Loss
Prevention of Bone LossCalciumHRTSERMSCalcitoninBisphosphonates
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Calcium Supplementation
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
HOPE Trial
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
PEPI Trial
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
BMD
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Spine BMD
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Total Hip BMD
Forearm BMD
WHI Results
WHI Results
Summary
Forearm BMD
WHI Results
WHI Results
Summary
WHI Results
WHI Results
Summary
WHI Results
Summary
Summary
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