Metabolic Bone Disease

Osteolysis(i.e.—hyperparathyroid states)

Defective Bone Formation

Inadequate mineralization of osteoid (RICKETS)

Defective osteoid production (aka Osteoporosis)

•Nutritional sec.•Renal sec.•Primary

•HAC•Osteogenesis imperfecta

•Renal sec.•Decr. Ca or P•VITAMIN D DEF.•Hepatic•anticonvulsant

Brinker, M. R. (2000). Basic sciences. In M. D. Miller & M. R. Brinker (Eds.), Review of orthopaedics (pp. 1-40). Saunders, Philadelphia

Brinker, M. R. (2000). Basic sciences. In M. D. Miller & M. R. Brinker (Eds.), Review of orthopaedics (pp. 1-40). Saunders, Philadelphia

Vitamin D functionsVitamin D functions

Regulates calcium and phosphorus levels in the body (calcium homeostasis)

Promotes absorption of calcium and phosphorus from the intestine

Increases bone mineralization Increases reabsorption of calcium and

phosphorus by renal tubules Maintains healthy bones and teeth

0 nM > 100 nM

Vitamin D and bone

RicketsSecondary

hyperparathyroidismImpaired intestinal calcium absorption

Reduced bone volume with normal mineralization

Osteopenia

USUALLY HYPOVITAMINOSIS D --inadequate intake --disorders of vitamin D metabolism --renal failure (decreased synth. Of 1, 25-(OH)2-vitD—the most active) Decreased Calcium or phosphorus intake

(e.g.—inappropriate feeding of renal diets)

Factors Effecting Vit. D Factors Effecting Vit. D StatusStatusFactors Effecting Vit. D Factors Effecting Vit. D StatusStatus

1)1) Geographic locationGeographic location

2)2) SeasonsSeasons

3)3) Skin pigmentationSkin pigmentation

4)4) Cultural practicesCultural practices

5)5) Living conditions/jobsLiving conditions/jobs

6)6) DietDiet

1)1) Geographic locationGeographic location

2)2) SeasonsSeasons

3)3) Skin pigmentationSkin pigmentation

4)4) Cultural practicesCultural practices

5)5) Living conditions/jobsLiving conditions/jobs

6)6) DietDiet

•Dietary•Renal failure•Liver disease•Pancreas/small intestinal dz•Hypoparathyroidism

METABOLIC CONTROLS of VIT. D ACTIONSMETABOLIC CONTROLS of VIT. D ACTIONS

25 (OH) D3

1, 25 (OH)1, 25 (OH)22 D3 D3

24, 25 (OH)2 D3KIDNEYKIDNEY ((--)) (+)(+)

BONEBONE OSTEOCLASTOSTEOCLAST activity

MATRIX BREAKDOWN

Ca++

OSTEOBLASTOSTEOBLAST differentiation

make more MATRIX

(+)(+)

(+)(+)

PTHPTH

(+)(+)

((--))(+)(+)

((--))

•Etiology of Hypophosphatemia

•Internal redistribution•Re-feeding•Acute respiratory alkalosis•Hungry bone syndrome

•Decreased intestinal absorption•Inadequate intake (< 100 mg/day)•Chronic diarrhea, malabsorption•Vitamin D deficiency or resistance•Aluminum or magnesium ingestion

•Increased urinary excretion•Primary hyperparathyroidism•Secondary hyperparathyroidism•Proximal tubule dysfunction•Hereditary hypophosphatemic rickets•Onchogenic osteomalacia

Clinical featuresClinical featuresRickets Soft bones Skeletal deformity

(bowed legs) Bone pain Increased tendency

of bone fractures Dental problems Muscle weakness Growth disturbance

Osteomalacia•Soft bones•Bone pain•Bone fractures•Compressed vertebrae•Muscle weakness

Loosers zones

Brinker, M. R. (2000). Basic sciences. In M. D. Miller & M. R. Brinker (Eds.), Review of orthopaedics (pp. 1-40). Saunders, Philadelphia

Renal Renal osteodystroosteodystrophyphy

Osteopenia, subcortical resorption, lucent metaphyseal bands, widening of metaphysis

"rugger jersey spine"

Osteomalacia and RicketsOsteomalacia and Rickets

Diagnosis: Measuring serum levels of:

› 25-hydroxycholecalciferol› PTH› Calcium› Phosphate› Alkaline phosphatase

Treatment principles for those with low vitamin D levels

Ergo- vs chole- calciferol

IM vs po administration

Daily vs intermittent dosing

Dose amount

Co-administration with Calcium

Cholecalciferol

Po

Intermittent

300,000 iu load

Separate

Comparing vitamin D therapies

Declarations

No pharmaceutical funding support for this talk

In last five years received honoraria, travel and subsistence expenses from: › Proctor and Gamble, Servier, Eli Lilly and

Novartis

Sunshine vitamin

This 73 year old lady was referred from her GP to ENT with deafness.

They asked her to see the rheumatologist

Why?

Paget’s Disease

Disease of bone remodeling

Accelerated bone resorption and formation

Disorganised mosaic pattern bone with increased vascularity and fibrosis

Cause unknown

› paramyxovirus, canine distemper

› Genetics- susceptibility loci More common in caucasian

M:F ratio 3:2 10% in over 70’s

Paget’s Disease: clinical manifestations

Bone pain

Joint pain

Deformity

Spontaneous fractures

Pagets Disease: complications

Fractures

Deafness

Nerve entrapment

Spinal stenosis

Cardiac failure

Osteogenic sarcoma

Hypercalcaemia (only if immobilized)

Paget’s Disease: investigations

Raised serum alk phos

Urinary hydroxyproline, pyridinoline cross-links

Radiology

› cortical thickening

› osteolytic, osteosclerotic and mixed lesions

› osteoporosis circumscripta

› bone scan

Normal

Courtesy of Pierre Delmas, MD.

Early-Stage (Lytic) Paget’s Disease: Tibia

V-shaped “blade of grass” lesion characteristic of lytic phase of Paget’s disease

Courtesy of Pierre Delmas, MD.

Advanced Paget’s Disease in the Tibia: Sclerotic and Lytic Lesions

Primarily sclerotic changes, with enlargement and thickening of long bones

Secondary osteolytic front

1976

Paget’s Disease: Progression Over 15 Years in Untreated Patient

Courtesy of Pierre Delmas, MD.1991

Bowing

Cortical thickening

Courtesy of Pierre Delmas, MD.

Early-Stage (Lytic) Paget’s Disease in the Skull: Known as “Osteoporosis Circumscripta”

Lytic border

Advanced (Sclerotic) Paget’s Disease: “Cotton Wool” Skull

Lyticlesion

Diffuse sclerotic changes

Courtesy of Pierre Delmas, MD.

Courtesy of Nuria Guañabens, MD.

Advanced Paget’s Disease in the Pelvis

Bony enlargement

Diffuse sclerotic changes

Courtesy of Nuria Guañabens, MD.

Paget’s Disease in the Femur

Curved deformity of the femur Cortical

thickening

Accentuation of trabecular pattern

Paget’s Disease: “Picture Frame” Vertebral Body

Courtesy of Pierre Delmas, MD.

Lytic lesion

Corticalthickening

Complications of Paget’s Disease: Fissure Fracture in the Tibia

Fissurefracture

Complications of Paget’s Disease: Complete (Chalk-Stick) Fracture in a Femur

Courtesy of Pierre Delmas, MD.

Paget’s Treatment

Bisphosphonates› calcitonin

Indicated if › Complications› Pain› Deformity› AP 2-3X Upper limit› Skull disease