Metabolic Bone Disorders

Prof. Mamoun KremliAlMaarefa College

Metabolic Bone Disorders

ObjectivesBone as an active tissue

Calcium is an important mineral

Calcium metaboism – normal control

DiseasesOsteoporosisRickets and OsteomalaciaHyperparathyroidismScurvy

Functions of bone tissueMechanical:

Support & protect soft tissueLoad transmissionMediate movement

Mineral reservoirLargest reservoir of CaRegulation of Ca

Basic Anatomy of Bone

http://classes.midlandstech.edu/

Bone componentsA: Matrix:

Organic: (40% of dry weight)Collagen fibersCells

Inorganic (Minerals): (60%)Ca hydroxyapetite, Ca phosphateOthers

B: Cells:Osteoblasts, osteoclasts, osteocytes, others

Bone cellsOsteoblasts

Osteoclasts

Osteocytes

Osteone:

a unit, not a cell

Bone is activeContinuous activity and flow

Structure and composition changing all the time

Regulations by regulating cellular activity:Osteoclasts & Osteoblasts

Cellular Activity

Modulation of Bone

Structure & Composition

Changes in mineral ion

concentrations

Hormones & Local Factors

Bone growth & remodellingGrowth:

Epiphyseal: Endochondral ossificationOn surface: Oppositional ossification

In Adults:Remodelling of existing bone (no growth)

Annually: 4% of cortical and 25% of cancellous“old bone” continuously replaced by “new bone”

Initially: formation slightly exceeds resorptionLater: resorption exceeds formation

Bone mass steadily declines

Age related bone changesChildhood – adolescence: Growth ( size & change shape)

Adolescence – 35 (40) years: Bones get heavier and stronger Annual bone mass gain: 3%

35 (40) – 50 years: Slow loss of bone mass annually: Men: 0.3% Women:

0.5% to menopause, then 3% for 10 years - (Why?) (↑ osteoclastic activity by ↓ hormones)

65 years – onwards: Loss of mass slows gradually to 0.5% (↓osteoblastic activity)

Body CalciumMost of Ca in body is present in bone

Release of Ca from bone is a slow process

Serum calcium is essential for cell function, nerve conduction, and muscle contractionNormal level: 8.8-10.4 mg/dl (2.2-2.6 mmol/L)S. levels have to be controlled quickly

Intestinal absorptionRenal reabsorption

Causes of Calcium absorption

intake of phosphates (as in soft drinks)

intake of oxalates (as in tea and coffee)

Drugs: corticosteroids

Intestinal malabsorption syndromes

Players in Ca regulationVit. D is the general crude regulator

Target organs:Small intestinesBones

PTH is the sensitive fine regulatorTarget organs:

Kidneys (v quick)Bones (slow)(indirectly): small intestine

Players in Ca regulationCacitonin: C cells of Thyroid

Opposite PTH on bone and kidneys

Oestrogen:Protects bone from PTH

Corticosteroids:Bad to bone

Local – BMP (Bone Morphogenic Proteins)

Mechanical stress:Strengthens bone

Calcium metabolism

http://www.google.com.sa/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=R103CHVWVmBSYM&tbnid=hbCOkisbVR50JM:&ved=0CAUQjRw&url=http://images.rheumatology.org/viewphoto.php?albumId=75677&imageId=2861766&ei=754AU4m_KuKM0AXC_ICACg&psig=AFQjCNGHei192PICxdAAxN1mKGFHxIe6cg&ust=1392635981102878

Hormonal regulation of Ca met.

Laboratory investigationsX-rays

Bone mineral density (BMD)DEXA scans: Dual Energy X0ray Absorptiometry

Biochemical tests:Serum Ca, PhosphateSerum Alkalin Phosphatase

Osteoclastic activity, measures bone turnover rateVit. D levelsUrine Ca and Phosphate excretionRenal profileLiver function test

Common DiseasesOsteoporosis

Rickets

Osteomalacia

Hyperparathyroidism (osteitis fibrosa)

OsteoporosisReduction of bone mass

Bone minerals and matrix both reducedMatrix present is normally mineralized

Types:Generalized:

systemic diseaseLocalized:

disuse (e.g. in cast)

http://drcecilia.ca/

OsteoporosisMore in women

Post menopausalOestrogen withdrawal

Increased with:cigarette smokingwhen start menopause with weak bones

In men:15 years later

In elderly, may be associated with osteomalacia

Osteoporosis – clinical featuresWeak bones: easily fractures:

Vertebral compression fractures Backache, kyphosis

Colle’s fractureNeck of femurProximal humerus

Orthopedic Radiology, A Greenspan. lippincott




http://library.med.utah.edu

Orthopedic Radiology, A Greenspan. lippincottwww.rcuv.org/tag/health





Orthopedic Radiology, A Greenspan. lippincottApley’s System of Prthop & Fractures




Loss of cortical thicknessseen on X-rays


Orthopedic Radiology, A Greenspan. lippincottApley’s System of Prthop & Fractures

Risk Factors for postmenopausal osteoporosis

Caucasian (white) or Asiatic ethnicity

F.H. of osteoporosis

H.O. anorexia nervosa or amenorrhea

Low peak bone mass in third decade

Early onset menopause

Very slim built

Oophorectomy and early hysterectomy

Nutritional deficiency

Chronic lack of exercise

Osteoporosis - PreventionGood Ca and Vit. D intake

Good physical activity

Exposure to sun

No smoking

No alcohol

http://dietitians-online.blogspot.com

Osteoporosis - PreventionIf BMD low:

Hormone replacement therapy (oestrogen):Effective earlyFor initial five yearsProblems:

Dysfunctional uterine bleedingRisk of uterine and breast cancer – on long use

Osteoporosis - treatmentTreat the fractures

Maintain good Ca and Vit D intakeMay be associated with osteomalacia

Maintain good physical activity

Trying to reduce rate of further bone lossHormone replacement therapyBisphosphonates

Rickets & Osteomalacia

Rickets & OsteomalaciaSame disease: (children / adults)

Inadequate absorption and/or utilization of Ca

Common causes:Lack of Vit. DSever Ca deficiencyHypophosphatemia

Results in loss of mineralization of bone

Rickets - pathologyMatrix forms, not calcified

In growing physisWidened physis (epiphyseal growth plate)Cupping of metaphyseal end (weak new bone)

In all boneOsteopenia, Thin cortex, Deformity

Harrisons sulcus, frontal bossing

In sever cases: hypocalcaemia:Tetany, convulsions, failure to thrive

Rickets – clinical pictureEnlarged ends of long bones

Wrists, knees

Rickety rosary:costo-chondral junctions

Harrisons sulcus

Frontal bossing

Bowing of legs:Localized – distal tibiae

In sever cases: tetany, convulsions



Wrists, knees


Harrisons sulcus

Frontal bossing



http://www.magazine.ayurvediccure.com/

www.thachers.org


Wrists, knees


Harrisons sulcus

Frontal bossing



www.thachers.org


Wrists, knees


Harrisons sulcus

Frontal bossing




Wrists, knees


Harrisons sulcus

Frontal bossing



N Engl J Med 2009

Rickets – X-raysWidened physis (epiphyseal growth plate)

metaphyseal end of physisCupping of (weak new bone)Irregular

Deformed bones


Rickets – X-rays


Rickets – lab resultsSerum Ca:

slightly low /or normal

Serum Phsphate:slightly low /or normal

Alk Phosphatase:High – a lot of bone turnover

Vit. D level: low

PTH level: Increased – scondary effect – to keep s. Ca level

Urinary Ca: V. low

Rickets - treatmentVit. D and Calcium

Most deformities correct graduallySever deformities might need surgical correction

Hopophsphataemic ricketsVit. D resistant rickets

Familial, X-linkedImpaired renal tubular reabsorption of phosphate

Lab. Results:Serum Phosphate: lowUrinary phosphate: high

Treatment:High dose Vit. DPhosphate

OsteomalaciaCaused by defective Vit. D:

Deficiency – lack of sun exposureIntestinal malabsorptionDefective formation of active Vit. D:

Liver or Renal disease

Clinical featuresBone aches – backache, hip pain

Compressed vertebral fractureInsufficiency fractures of femur / tibia


Osteomalacia – X-raysWeak osteopaenic bone

Biconcave vertebrae & compression fractures

Trefoil pelvis – acetabular protrusion

Typically: Looser’s zones:Poorly healing stress fractures

Neck of scapulaNeck of femurPubic bones

Apley’s System of Prthop & Fractures






Apley’s System of Prthop & Fractures

http://www.omjournal.org

Osteomalacia – X-raysLooser’s zone


HyperparathyroidismPrimary:

Parathyroid adenoma / hyperplasis

Secondary:Hyperplasia due to hypocalcaemia

Tertiary:Autonomous activity after secondary hyperplasis

HyperparathyroidismEffect of PTH

Target organs:KidneysBonesIntestines (indirect)

Bone weakens, resorptionIncreased serum Ca


HyperparathyroidismBones

RarefactionSubperiosteal resorption (middle phalanges)Reorption of lateral end clavicleBrown tumors

StonesKidney stones and nephroclacinosis

MoansAbdominal pain, renal pain

GroansPschological depression, stress

Hyperparathyroidism – x-raysBones

RarefactionBone resorption

Subperiosteal resotptionmiddle phalangesTibial shaft

lateral end clavicleBrown tumorsSkull: salt & pepper

Soft tissue calcification

www.eurorad.org





Soft tissue calcificationOrthopedic Radiology, A Greenspan. lippincott

Hyperparathyroidism – x-raysSubperiosteal bone resorption






Soft tissue calcification Orthopedic Radiology, A Greenspan. lippincott






http://www.radpod.org/2008





Soft tissue calcificationOrthopedic Radiology, A Greenspan.

lippincott





Soft tissue calcificationOrthopedic Radiology, A Greenspan. lippincott

Hyperparathyroidism - treatment

Hydration

Reduced calcium intake

If adenoma:Surgical removalBeware of the “hungry bone” syndrome post

operatively – severe hypocalcaemia (why?)

Scurvy – Vit. C deficiencyFirst discovered in sailors

Failure of collagen fibers formation

Weak osteoid matrix

Clinical picture:Child irritable, anemiaBleeding gumsPain and swellings at ends of long bones

Scurvy – Vit. C deficiencyX-rays:

Osteopaenia – more at mataphysisSub-periosteal bleeding

Periosseous calcificationRing epiphysisSclerosis at juxtaepiphyseal metphysis

Treatment:Vit C (large doses)

Scurvy – Vit. C deficiency


Scurvy – Vit. C deficiencyX-rays:

Osteopaenia – more at mataphysisSub-periosteal bleeding

Periosseous calcificationRing epiphysisSclerosis at juxtaepiphyseal metphysis

Treatment:Vit C (large doses)

SummaryBone is an active tissue

Continuous absorption and rebuilding

Calcium is an important mineral

Calcium control

DiseasesOsteoporosisRickets and OsteomalaciaHyperparathyroidismScurvy

Metabolic Bone Disorders

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