Bone mineral homeostasis

Mr. Ujjal Bose

Lecturer

KMCIC

Calcium : 1-2kg

Phosphate: 1kg

Calcium: plasma Ca is regulated by PTH, Vit D,& calcitonin

Uses: tetanyOsteoporosisDietary supplementParathyroid hormone:Secretion regulated by plasma Ca levelsRegulates Ca and phosphate influx across cellular

membranes in bone & kidneyActions:Bone: increases bone resorption by increasing the no. &

activity of osteoclastsKidney: increases the reabsortion of Ca & reduces that of

phosphateStimulates the production of 1,25-dihydroxyvitamin DIntestines: indirectly increases absorption of caTeriparatide: 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 DD3 - cholecalciferolD2 – ergocalciferaolActivation of Vit D: hydroxylated in the liver to 25-

hydroxyvitamin D → 1,25-dihydroxyvitamin D (calcitriol)Actions:Intestine: increases the absorption of Ca and PO4 Bone: increases Ca & PO4 resorptionKidney: excretion of Ca & PO4 is decreased

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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 deficiencyRickets:Vit D resistant ricketsVit D dependent ricketsRenal ricketshypoparathyroidism

Calcitonin: Secreted by parafollicular ‘C’ cells of thyroid Regulated by plasma Ca levelsActions:bone: inhibits osteoclastic bone resorptionKidney: Inhibits reabsortion of Ca & PO4

Bisphosphonates: etidronate, pamidronate, alendronate, risendronate

Mechanism: retard formation and dissolution of hydroxyapatite crystals

Localize to regions of osteoclastsblock farnesyl pyroposphateUse: osteoporosis Paget’s diseaseHypercalcemia of malignancyOsteoclastic bone metastasis

Adverse effects: gastric irritationCalcimimetics: Cinacalcet: activates calcium sensing

receptor on parathyroid glandBlocks PTH secretionUse: secondary hyperparathyroidism in

chronic kidney diseaseParathyroid carcinomaPlicamycin: cytotoxic antibioticUse: hypercalcemiaPaget’s disease