Endocrine Pharmacology: Calcium Homeostasis

Hormonal Regulators of Ca+2 Metabolism and Bone Mineral Homeostasis

• Parathormone (PTH) is a single chain polypeptide secreted by the parathyroid glands.

• Synthetic PTH (teriparatide) is used in treatment of osteoporosis, but has a risk of osteosarcoma with long-term use.

• PTH increases serum calcium by increasing calcium reabsorption in the kidney, stimulating bone resorption, and stimulating vitamin D activation.

• Low intermittent doses of PTH produce an increase in bone formation.

• Calcitonin (CT) is a single chain polypeptide secreted by the C-Cells of the thyroid.

• Calcitonin decreases serum calcium by decreasing calcium reabsorption in the kidney and inhibiting bone resorption.

• Salmon CT is used in treatment of hypercalcemia and osteoporosis.

• Vitamin D is a fat-soluble vitamin found in two forms: Vitamin D2 (plants) and Vitamin D3 (animals and human skin).

• Vitamin D increases serum calcium by increasing calcium absorption from the intestine and decreasing its excretion by the kidney.

• Vitamin D is used in treatment of hypocalcemia, osteoporosis, and rickets.

• Glucocorticoids can cause osteoporosis in adults and retarded growth in children due to increased renal Ca2+ excretion and decreased bone formation.

• Estrogen decreases bone resorption and is used in treatment of postmenopausal osteoporosis.

• Selective estrogen receptor modulators (Raloxifene) stimulate estrogen receptors in bones and block them in the breast and uterus.

Non-Hormonal Regulators of Ca2+ Metabolism and Bone Mineral Homeostasis

• Bisphosphonates (Alendronate) inhibit bone resorption by stimulating osteoclast apoptosis.

• Bisphosphonates are used in treatment of hypercalcemia associated with malignancy and bone lesions associated with bone metastasis, and treatment of osteoporosis.

• Bisphosphonates can cause renal impairment and osteonecrosis of the jaw as side effects.

• Thiazide and furosemide are used to treat hypercalcemia by increasing urine flow and enhancing Ca2+ excretion.

• Fluoride is used to treat osteoporosis.

• Hypercalcemia is caused by hyperparathyroidism or malignancy in 90% of cases.

• Treatment of hypercalcemia includes diuresis, hydrocortisone, intravenous bisphosphonates, and hemodialysis.

• Hypocalcemia is caused by hypoparathyroidism, chronic renal failure, and vitamin D deficiency, and is treated with a diet rich in calcium and calcium gluconate.