Bone Mineral Homeostasis

Bone mineral homeostasis Mr. Ujjal Bose Lecturer KMCIC

Calcium : 1-2kg Phosphate: 1kg Calcium: plasma Ca is regulated by PTH, Vit D,& calcitonin

Uses: tetany Osteoporosis Dietary supplement Parathyroid hormone: Secretion regulated by plasma Ca levels Regulates Ca and phosphate influx across cellular membranes in bone & kidney Actions: Bone: increases bone resorption by increasing the no. & activity of osteoclasts Kidney: increases the reabsortion of Ca & reduces that of phosphate Stimulates the production of 1,25-dihydroxyvitamin D Intestines: indirectly increases absorption of ca Teriparatide: recombinant PTH

Clinical features of acute Hypoparathyroidism • Hypocalcemia • Tetany • Carpopedal spasm • Laryngospasm • Tingling of lips, hands, muscles • Convulsions

Clinical features of chronic Hypoparathyroidism

• Loss of hair • Brittle finger nails • Caries teeth • Cataract • Anxiety & Depression

Vitamin D D3 - cholecalciferol D2 – ergocalciferaol Activation of Vit D: hydroxylated in the liver to 25hydroxyvitamin D → 1,25-dihydroxyvitamin D (calcitriol) Actions: Intestine: increases the absorption of Ca and PO4 Bone: increases Ca & PO4 resorption Kidney: excretion of Ca & PO4 is decreased • •

Preparations of Vitamin D • Ergocalciferol (Vit. D2):Oral capsules- 400 IU/day for prevention of rickets in children and osteomalacia in adults. • Cholecalciferol (Vit D3): oral and IM injection Prodrugs, orally effective and are rapidly biotransformed into calcitriol in the liver. They are effective in renal bone disease and hypoparathyroidism • Calcitriol: oral capsules and solution Alfacalcidol Dihydrotachysterol • Calcipotriol: Vit D analogue used topically in psoriasis.

Uses: Prophylaxis & treatment of Vit D deficiency Rickets: Vit D resistant rickets Vit D dependent rickets Renal rickets hypoparathyroidism

Calcitonin: Secreted by parafollicular ‘C’ cells of thyroid Regulated by plasma Ca levels Actions: bone: inhibits osteoclastic bone resorption Kidney: Inhibits reabsortion of Ca & PO4 Bisphosphonates: etidronate, pamidronate, alendronate, risendronate Mechanism: retard formation and dissolution of hydroxyapatite crystals Localize to regions of osteoclasts block farnesyl pyroposphate Use: osteoporosis Paget’s disease Hypercalcemia of malignancy Osteoclastic bone metastasis

Adverse effects: gastric irritation Calcimimetics: Cinacalcet: activates calcium sensing receptor on parathyroid gland Blocks PTH secretion Use: secondary hyperparathyroidism in chronic kidney disease Parathyroid carcinoma Plicamycin: cytotoxic antibiotic Use: hypercalcemia Paget’s disease