1. Metabolic Bone Disorders Prof. Mamoun Kremli AlMaarefa College

2. Objectives • Bone as an active tissue • Calcium is an important mineral • Calcium metabolism – normal control • Diseases • Osteoporosis • Rickets and Osteomalacia • Hyperparathyroidism • Scurvy

3. Functions of bone tissue • Mechanical: • Support & protect soft tissue • Load transmission • Mediate movement • Mineral reservoir • Largest reservoir of Ca++ • Regulation of Ca++

4. Bone components A: Matrix: • Organic: (40% of dry weight) • Collagen fibers • Cells • Inorganic (Minerals): (60%) • Ca++ hydroxyapatite, Ca++ phosphate • Others B: Cells: • Osteoblasts, osteoclasts, osteocytes, others

5. Bone is active • Continuous activity and flow • Structure and composition changing all the time • Regulations by regulating cellular activity: • Osteoclasts & Osteoblasts

6. Bone growth & remodelling • Growth: • Epiphyseal: • Endochondral ossification • On surface: • Oppositional ossification Miller Review of Orthopaedics

7. Bone growth & remodeling • In Adults: • Remodeling of existing bone (no growth) • Annually: • 4% of cortical and • 25% of cancellous • “old bone” continuously replaced by “new bone” • Initially: formation slightly exceeds resorption • Later: resorption exceeds formation • Bone mass steadily declines

8. Bone Regulation Miller Review of Orthopaedics

9. Age related Bone Changes • Childhood – 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)

10. Change in BMD (mean ± 1SD) with age in healthy male (--) and female (--)(DPX, Lunar) BMD, g/cm2 TOTAL BODY FEMORAL NECK LUMBAR SPINE Age (yrs)

11. Body Calcium • Most of Calcium in body is present in bone • Release of Calcium from bone is a slow process • Serum calcium is essential for cell function, nerve conduction, and muscle contraction • Normal level: 8.8-10.4 mg/dl (2.2-2.6 mmol/L) • Calcium serum levels have to be controlled quickly • Renal reabsorption • Intestinal absorption

12. Causes of Calcium absorption •  intake of phosphates (as in soft drinks) •  intake of oxalates (as in tea and coffee) • Drugs: corticosteroids • Intestinal ma-labsorption syndromes

13. Players in Ca regulation • Vit. D is the general crude regulator • Target organs: • Small intestines • Bones • PTH is the sensitive fine regulator • Target organs: • Kidneys (v. quick) • Bones (slow) • (indirectly): small intestine

14. Players in Ca regulation • Cacitonin: C cells of Thyroid • Opposite PTH on bone and kidneys • Good to bone • Oestrogen: • Protects bone from PTH • Good to bone

15. Players in Ca regulation • Corticosteroids: • Bad to bone • Reduce osteoblastic activity, and increases osteoclastic activity • Reduce calcium absorption from intestine, and increase renal excretion of calcium • Local – BMP (Bone Morphogenic Proteins) • Mechanical stress: • Strengthens bone

16. Calcium metabolism

18. Hormonal regulation of Ca met.

19. Hormonal regulation of Ca met. Mesutti, 2011

20. Miller Review of Orthopaedics

21. Laboratory investigations • X-rays • Bone mineral density (BMD) • DEXA scans: Dual Energy Xray Absorptiometry • Biochemical tests: • Serum Ca, Phosphate • Serum Alkaline Phosphatase • Osteoclastic activity, measures bone turnover rate • Vit. D levels • Urine Ca and Phosphate excretion • Renal profile • Liver function test

22. Common Diseases • Osteoporosis • Rickets • Osteomalacia • Hyperparathyroidism (osteitisfibrosa)

23. Osteoporosis • Reduction of bone mass • Bone minerals and matrix both reduced • Matrix present is normally mineralized • Types: • Generalized: • systemic disease • Localized: • disuse (e.g. in cast) http://drcecilia.ca/

24. Osteoporosis • More in women • Post menopausal • Oestrogen withdrawal • Increased with: • cigarette smoking • when start menopause with weak bones • In men: • 15 years later • In elderly, may be associated with osteomalacia

25. Osteoporosis – clinical features • Weak bones: easily fractures: • Vertebral compression fractures • Backache, kyphosis • Colle’s fracture • Neck of femur • Proximal humerus Orthopedic Radiology, A Greenspan. lippincott

26. Osteoporosis – clinical features • Weak bones: easily fractures: • Vertebral compression fractures • Backache, kyphosis • Colle’s fracture • Neck of femur • Proximal humerus http://library.med.utah.edu www.rcuv.org/tag/health Orthopedic Radiology, A Greenspan. lippincott

27. Osteoporosis – clinical features • Weak bones: easily fractures: • Vertebral compression fractures • Backache, kyphosis • Colle’s fracture • Neck of femur • Proximal humerus http://library.med.utah.edu Apley’s System of Prthop & Fractures Orthopedic Radiology, A Greenspan. lippincott

28. Osteoporosis – clinical features • Weak bones: easily fractures: • Vertebral compression fractures • Backache, kyphosis • Colle’s fracture • Neck of femur • Proximal humerus • Loss of cortical thickness • seen on X-rays Orthopedic Radiology, A Greenspan. lippincott

29. 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

30. 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

31. Osteoporosis - Prevention • Good Ca and Vit. D intake • Good physical activity • Exposure to sun • No smoking • No alcohol http://dietitians-online.blogspot.com

32. Osteoporosis - Prevention • If BMD low: • Hormone replacement therapy (estrogen): • Effective early • For initial five years • Problems: • Dysfunctional uterine bleeding • Risk of uterine and breast cancer – on long use

33. Osteoporosis - Treatment • Treat the fractures • Maintain good Ca and Vit D intake • May be associated with osteomalacia • Maintain good physical activity • Trying to reduce rate of further bone loss • Hormone replacement therapy • Bisphosphonates

34. Rickets & Osteomalacia

35. Rickets & Osteomalacia • Same disease: (children / adults) • Inadequate absorption and/or utilization of Ca • Common causes: • Lack of Vit. D • Sever Ca deficiency • Hypophosphatemia • Results in loss of mineralization of bone

36. Nutritional Calcium Deficiency Miller Review of Orthopedics

37. Rickets - pathology • Matrix forms, not calcified • In growing physis • Widened physis (epiphyseal growth plate) • Cupping of metaphyseal end (weak new bone) • Irregular metaphyseal end Orthopedic Radiology, A Greenspan. lippincott

38. Rickets - pathology • Matrix forms, not calcified • In growing physis • Widened physis (epiphyseal growth plate) • Cupping of metaphyseal end (weak new bone) • Irregular metapyseal end • In all bone • Osteopenia, Thin cortex, Deformity • Harrisons sulcus, frontal bossing • In sever cases: hypocalcaemia: • Tetany, convulsions, failure to thrive

39. Rickets – clinical picture • Enlarged ends of long bones • Wrists, knees • Rickety rosary: • costo-chondral junctions • Harrison’s sulcus • Frontal bossing • Bowing of legs: • Localized – distal tibiae • In sever cases: tetany, convulsions Orthopedic Radiology, A Greenspan. lippincott

40. Rickets – clinical picture • Enlarged 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 http://www.magazine.ayurvediccure.com/ www.thachers.org

41. Rickets – clinical picture • Enlarged 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 www.thachers.org

42. Rickets – clinical picture • Enlarged 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 www.thachers.org

43. Rickets – clinical picture • Enlarged 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

44. Rickets – clinical picture • Enlarged 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 N Engl J Med 2009

45. Rickets – X-rays • Widened physis(epiphyseal growth plate) • metaphyseal end of physis • Cupping of (weak new bone) • Irregular • Deformed bones Orthopedic Radiology, A Greenspan. lippincott

46. Rickets – X-rays Orthopedic Radiology, A Greenspan. lippincott

47. Rickets – X-rays Orthopedic Radiology, A Greenspan. lippincott

48. Rickets – lab results • Serum 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

49. Rickets - treatment • Vit. D and Calcium • Most deformities correct gradually • Sever deformities might need surgical correction

50. Hopophsphataemic rickets • Vit. D resistant rickets • Familial, X-linked • Impaired renal tubular reabsorption of phosphate • Lab. Results: • Serum Phosphate: low • Urinary phosphate: high • Treatment: • High dose Vit. D • Phosphate