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Bone Metabolism

Bone Metabolism. CM Robinson Senior Lecturer Royal Infirmary of Edinburgh. Outline. Normal bone structure Normal calcium/phosphate metabolism Presentation and investigation of bone metabolism disorders Common disorders of bone metabolism. Normal Bone Structure.

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Bone Metabolism

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  1. Bone Metabolism CM Robinson Senior Lecturer Royal Infirmary of Edinburgh

  2. Outline • Normal bone structure • Normal calcium/phosphate metabolism • Presentation and investigation of bone metabolism disorders • Common disorders of bone metabolism

  3. Normal Bone Structure • What are the normal types of bone in the mature skeleton? • Lamellar • Cortical • Cancellous • Woven • Immature • Healing • Pathological

  4. What is the composition of bone? • The matrix • 40% organic • Type 1 collagen (tensile strength) • Proteoglycans (compressive strength) • Osteocalcin/Osteonectin • Growth factors/Cytokines/Osteoid • 60% inorganic • Calcium hydroxyapatite • The cells • osteo-clast/blast/cyte/progenitor

  5. Bone structure • Structure of lamellar bone? • Structure of woven bone?

  6. Bone turnover • How does normal bone grow…….. • In length? • In width? • How does normal bone remodel? • How does bone heal?

  7. Bone turnover • What happens to bone………. • in youth? • aged 20-40’s? • aged 40+? • aged over 70?

  8. Calcium metabolism • What is the recommended daily intake? • 1000mg • What is the plasma concentration? • 2.2-2.6mmol/L • How is calcium excreted? • Kidneys - 2.5-10mmol/24 hrs • How are calcium levels regulated? • PTH and vitamin D (+others)

  9. Phosphate metabolism • Normal plasma concentration? • 0.9-1.3 mmol/L • Absorption and excretion? • Gut and kidneys • Regulation • Not as closely regulated as calcium but PTH most important

  10. PTH • Physiological role • Production related to plasma calcium levels • Control of calcium levels • target organs • bone - increased Ca/PO4 release • kidneys • increased reabsorption of Ca • increased excretion of PO4 • gut - indirect increase in calcium reabs by stimulting activation of vitamin D metabolism

  11. Calcitonin • Physiological role • Levels increased when serum Ca >2.25mmol/L • Target organs • Bone - suppresses resorption • Kidney - increases excretion

  12. Vitamin D (cholecalciferol) • Sources of vit D • Diet • u.v. light on precursors in skin • Normal daily requirement • 400IU/day • Target organs • bone - increased Ca release • gut - increased Ca absorption

  13. Normal metabolism Vit D 25-HCC (Liver) Ca/PTH 1,25-DHCC 24,25-DHCC (Kidney) (Kidney)

  14. Factors affecting bone turnover • Other hormones • Oestrogen • gut - increased absorption • bone - decreased re-absorption • Glucocorticoids • gut - decrease absorption • bone - increased re-absorption/decreased formation • Thyroxine • stimulates formation/resorption • net resorption

  15. Factors affecting bone turnover • Local factors • I-LGF 1 (somatomedin C) • increased osteoblast prolifn • TGF • increased osteoblast activity • IL-1/OAF • increased osteoclast activity (myeloma) • PG’s • increased bone turnover (#’s/inflammn) • BMP • bone formation

  16. Factors affecting bone turnover • Other factors • Local stresses • Electrical stimuln • Environmental • temp • oxygen levels • acid/base balance

  17. Bone metabolic disorders • Presentation? • Skeletal abnormality • osteopenia - osteomalacia/osteoporosis • osteitis fibrosa cystica - replacement of bone with fibrous tissue usually due to PTH excess • Hypercalcaemia • Underlying hormonal disorder • When to investigate? • Under 50 • repeated fractures or deformity • systemic features or signs of hormonal disorder

  18. Bone metabolic disorders • Assessment • History • duration of sx • drug rx • causal associations • Examn • X-rays - plain and specialist (cort index/Singh index/DEXA) • Biochemical tests • Bone biopsy

  19. Biochemical tests • Which investigations? • Ca/PO4 - plasma/excretion • Alkaline phosphatase/osteocalcin (o’blast activity) • PTH • vit D uptake • hydroxyproline excretion

  20. Osteoporosis • Definition? • Decrease in bone mass per unit volume • Fragility (perfn of trabecular plates) • Primary (post-menopausal/senile) Secondary

  21. Primary osteoporosis • Post-menopausal • Aetiology? • Menopausal loss 3% vs 0.3% previously • Loss of oestrogen - incr osteoclastic activity • Risk factors? • Race • Heredity • Build • Early menopause/hysterectomy • Smoking/alcohol/drug abuse • ?Calcium intake

  22. Primary osteoporosis • Post-menopausal • Clinical features? • Prevention and treatment? • General health measures/diet • HRT • Bisphosphonates • Calcium • Vitamin D

  23. Primary osteoporosis • Senile • Aetiology? • 7-8th decade steady loss of 0.5% • physiological manifestation of aging • Risk factors? • Prolonged uncorrected post-menopausal loss • chronic illness • urinary insuff • muscle atrophy • diet def/lack of exposure to sun/mild osteomalacia

  24. Primary osteoporosis • Senile • Clinical features? • as for post-menopausal • Treatment? • general health measures • treat fractures • as for post-menopausal (HRT not acceptable)

  25. Secondary Osteoporosis • Aetiology? • Nutrition - scurvy, malnutr,malabs • Endocrine - Hyper PTH, Cush, Gonad, Thyroid • Drug induced - steroid, alcohol, smoking, phenytoin • Malignancy - ca’tosis, myeloma (o’clasts), leukaemia • Chronic disease - RA, AS, TB, CRF • Idiopathic - juvenile, post-climacteric • Genetic -OI • Clin features? • Investigation? • Treatment?

  26. Osteomalacia • Definition? • Rickets - growth plates affected, children • Osteomalacia - incomplete mineralisation of osteoid, adults • Types - vit D def, vit-D resist (fam hypophos) • Aetiology? • Decr intake/production(sun/diet/malabs) • Decreased processing (liver/kidney) • Increased excretion (kidney)

  27. Osteomalacia • Clinical features? • In child • In adult • Investign • Ca/PO4 decr, alk ph incr, Ca excr decr • Ca x PO4 <2.4 • Bone biopsy

  28. Osteomalacia • Types • Vitamin D deficient • Hypophosphataemic • growth decr +++ and severe deformity with wide epiphyses • x-linked dominant • decreased tubular reabs of PO4 • Ca normal but low PO4 • Rx PO4 and vit D

  29. Osteomalacia vs osteoporosis Osteomal Osteopor Ageing fem, #, decreased bone dens Ill Not ill General ache Asympt till # Weak muscles normal Loosers nil Alk ph incr normal PO4 decr normal Ca x PO4 <2.4 Ca x PO4 >2.4

  30. Hyperparathyroidism • Excessive PTH • Due to prim (adenoma), sec (hypocalc), tert (second hyperact -> autonomous overact) • Osteitis due to fibr repl of bone • Clin feat - hypercalc • Invest - Calc incr, PO4 decr, incr PTH • Rx surg

  31. Renal osteodystrophy • Combination of • osteomalacia • secondary PTH incr • osteoporosis/sclerosis • CF - renal disorder, depends on predom pathology • Rx - vit D or 1,25-DHCC • renal disorder correction

  32. Pagets • Bone enlargement and thickening • Incr o-clast/blast activity -> increased tunrover • Aet - unknown but racial diff ?viral • CF - M=F, >50, ache but not severe unless fracture or tumour • Inv - x-ray app characteristic, alk ph is increased and increased hydroxyproline in urine • Rx - bisphos, calcitonin

  33. Endocrine disorders • Cushings • Hypopituitarism - GH def - prop dwarf or Frohlich adiposogenital syndrome • Hyperpituitarism - gigantism or acromegaly • Hypothyroidism - cretinism or myxoedema • Hyperthyroidism - o’porosis • Pregnancy - backache, CTS, rheumatoid improves SLE gets worse

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