Metabolic Bone Disorders

1. Metabolic Bone Disorders Prof. Mamoun Kremli AlMaarefa College

2. Objectives • Bone as an active tissue • Calcium is an important mineral • Calcium metaboism – 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. Basic Anatomy of Bone http://classes.midlandstech.edu/

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

6. Bone cells • Osteoblasts • Osteoclasts • Osteocytes • Osteone: a unit, not a cell

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

8. Bone growth & remodelling • Growth: • Epiphyseal: Endochondral ossification • On 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 resorption • Later: resorption exceeds formation • Bone mass steadily declines

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. Body Calcium • Most 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 contraction • Normal level: 8.8-10.4 mg/dl (2.2-2.6 mmol/L) • S. levels have to be controlled quickly • Intestinal absorption • Renal reabsorption

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

12. 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

13. Players in Ca regulation • Cacitonin: 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

14. Calcium metabolism

15. Hormonal regulation of Ca met.

17. Laboratory investigations • X-rays • Bone mineral density (BMD) • DEXA scans: Dual Energy X0ray Absorptiometry • Biochemical tests: • Serum Ca, Phosphate • Serum AlkalinPhosphatase • Osteoclastic activity, measures bone turnover rate • Vit. D levels • Urine Ca and Phosphate excretion • Renal profile • Liver function test

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

19. 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/

20. 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

21. 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

22. 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

23. 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 Orthopedic Radiology, A Greenspan. lippincott Apley’s System of Prthop & Fractures

24. 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 http://library.med.utah.edu Orthopedic Radiology, A Greenspan. lippincott Apley’s System of Prthop & Fractures

25. 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

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

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

28. 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

29. Rickets & Osteomalacia

30. 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

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

32. 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 Orthopedic Radiology, A Greenspan. lippincott

33. 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

34. 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

35. 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

36. 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

37. 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

38. 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

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

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

41. 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. Calevel • Urinary Ca: V. low

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

43. 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

44. Osteomalacia • Caused by defective Vit. D: • Deficiency – lack of sun exposure • Intestinal malabsorption • Defective formation of active Vit. D: • Liver or Renal disease • Clinical features • Bone aches – backache, hip pain • Compressed vertebral fracture • Insufficiency fractures of femur / tibia Orthopedic Radiology, A Greenspan. lippincott

45. Osteomalacia – X-rays • Weak osteopaenic bone • Biconcave vertebrae & compression fractures • Trefoil pelvis – acetabular protrusion • Typically: Looser’s zones: • Poorly healing stress fractures • Neck of scapula • Neck of femur • Pubic bones Apley’s System of Prthop & Fractures

46. Osteomalacia – X-rays • Weak osteopaenic bone • Biconcave vertebrae & compression fractures • Trefoil pelvis – acetabular protrusion • Typically: Looser’s zones: • Poorly healing stress fractures • Neck of scapula • Neck of femur • Pubic bones Apley’s System of Prthop & Fractures

47. Osteomalacia – X-rays • Weak osteopaenic bone • Biconcave vertebrae & compression fractures • Trefoil pelvis – acetabular protrusion • Typically: Looser’s zones: • Poorly healing stress fractures • Neck of scapula • Neck of femur • Pubic bones Orthopedic Radiology, A Greenspan. lippincott

48. Osteomalacia – X-rays • Weak osteopaenic bone • Biconcave vertebrae & compression fractures • Trefoil pelvis – acetabular protrusion • Typically: Looser’s zones: • Poorly healing stress fractures • Neck of scapula • Neck of femur • Pubic bones http://www.omjournal.org Apley’s System of Prthop & Fractures

49. Osteomalacia – X-rays • Looser’s zone Orthopedic Radiology, A Greenspan. lippincott