METABOLIC BONE DISEASES Amro Al-Hibshi, MD, FRCSC, MEd

PHYSIOLOGY Calcium Calcium Phosphate Phosphate PTH PTH Vitamin D Vitamin D Calcitonin Calcitonin

Calcium > 99% in bone > 99% in bone Muscle and nerve function Muscle and nerve function Clotting mechanisms Clotting mechanisms Free plasma Ca = Bound plasma Ca Free plasma Ca = Bound plasma Ca Active transport absorption in the duodenum and passive diffusion in the jejunum Active transport absorption in the duodenum and passive diffusion in the jejunum 98% reabsorption in the kidney 98% reabsorption in the kidney

Calcium Requirement 600 mg/day in children 600 mg/day in children 1300 mg/day in adolescents and young adults 1300 mg/day in adolescents and young adults 750 mg/day in adults 750 mg/day in adults 1500 mg/day in pregnant women 1500 mg/day in pregnant women 2000 mg/day in lactating women 2000 mg/day in lactating women 1500 mg/day in postmenopausal women and patients with fractures 1500 mg/day in postmenopausal women and patients with fractures

PHOSPHATE Key component of bone mineral Key component of bone mineral Enzyme systems and molecular interactions Enzyme systems and molecular interactions 85% in bone 85% in bone Plasma Phosphate is mostly unbound Plasma Phosphate is mostly unbound mg/day mg/day

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

Hypercalemia Primary hyperparathyroidism Primary hyperparathyroidism Familial syndromes Familial syndromes Malignancy and other causes Malignancy and other causes

Hypercalcemia Polyurea Polyurea Kidney stones Kidney stones Excessive bony resorption Excessive bony resorption Confusion, stupor and weakness Confusion, stupor and weakness Constipation Constipation

Primary Hyperparathyroidism Parathyroid adenoma Parathyroid adenoma Increased plasma calcium and decreased phosphate Increased plasma calcium and decreased phosphate Increased osteoclastic resorption Increased osteoclastic resorption Osteopenia, fibrous replacement, brown tumors and chondrocalcinosis Osteopenia, fibrous replacement, brown tumors and chondrocalcinosis Surgical parathyroidectomy Surgical parathyroidectomy

Familial syndromes MEN MEN Familial hypocalciuric hypercalcemia Familial hypocalciuric hypercalcemia

Other Causes PTH-related protein PTH-related protein Lysis Lysis Vitamin D intoxication Vitamin D intoxication Prolonged immobilization Prolonged immobilization Addison’s Addison’s Milk alkali syndrome Milk alkali syndrome Kidney disease Kidney disease Sarcoidosis Sarcoidosis

Treatment Hydration Hydration Diuretics Diuretics Dialysis (for severe cases) Dialysis (for severe cases) Specific drug therapy Specific drug therapy

HYPOCALCEMIA Increased neuromuscular irritability Increased neuromuscular irritability Cataracts Cataracts Fungal infections of the nails Fungal infections of the nails EKG changes EKG changes

HYPOCALCEMIA Hypoaparathyroidism Hypoaparathyroidism Pseudohypoparathyroidism Pseudohypoparathyroidism Renal osteodystrophy Renal osteodystrophy Rickets / Osteomalacia Rickets / Osteomalacia

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

Renal Osteodystrophy Diminished renal P excretion Diminished renal P excretion Increased Ca excretion Increased Ca excretion Impaired synthesis of Vit D Impaired synthesis of Vit D Toxicity e.g. Aluminum and amyloidosis Toxicity e.g. Aluminum and amyloidosis

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

Rickets / Osteomalacia Increased width and disorientation in the physis Increased width and disorientation in the physis Cortical thinning and bowing Cortical thinning and bowing Retarded bone growth Retarded bone growth Muscle hypotonia Muscle hypotonia Dental disease Dental disease Pathologic fractures Pathologic fractures

Rickets / Osteomalacia Low normal Ca (maintained by high PTH) Low normal Ca (maintained by high PTH) Low P Low P High PTH High PTH Low vitamin D Low vitamin D

Osteoporosis Decrease in bone mass Decrease in bone mass Women / smokers / EtOH Women / smokers / EtOH Fractures: Hip, distal radius and vertebrae Fractures: Hip, distal radius and vertebrae DEXA DEXA Treatment: Bisphosphonates Treatment: Bisphosphonates Estrogen-progesterone therapy should be started within 6 years of menopause Estrogen-progesterone therapy should be started within 6 years of menopause

Brinker, M. R. (2000). Basic sciences. In M. D. Miller & M. R. Brinker (Eds.), Review of orthopaedi cs (pp ). Saunders, Philadelphi a