Calcitonin

Calcitonin (Miacalcin) is an FDA-approved 32 amino acid polypeptide hormone used for the treatment of postmenopausal osteoporosis, Paget's disease of bone, and hypercalcemia. The commercially used form is synthetic salmon calcitonin, which is approximately 40–50 times more potent than human calcitonin on a weight basis and has a longer duration of action, making it clinically preferable.

Calcitonin binds to specific calcitonin receptors (CTRs) expressed predominantly on osteoclasts, the bone-resorbing cells. Receptor activation via Gs-coupled cAMP signaling and Gq-coupled phospholipase C activation leads to a rapid cytoskeletal reorganization in osteoclasts — the ruffled border retracts and the cell loses its characteristic polarized morphology. This functional inactivation halts the secretion of hydrochloric acid and cathepsin K that drive bone matrix dissolution. With sustained exposure, osteoclast cell numbers also decrease. The net effect is reduced bone resorption and a fall in serum calcium and phosphate. In the kidney, calcitonin promotes renal excretion of calcium, phosphate, sodium, magnesium, and potassium by inhibiting tubular reabsorption. Calcitonin also has central analgesic properties, mediated through elevated beta-endorphin levels, contributing to its use in Paget's disease-associated bone pain.

The PROOF study (5 years, 1,255 postmenopausal women) demonstrated that 200 IU/day intranasal calcitonin reduced vertebral fracture risk by 33% compared to placebo. Lumbar spine bone mineral density increased modestly (+1.5% over 5 years). However, subsequent reviews by the FDA (2013) identified a possible increased risk of malignancy with long-term use, leading to a label update. Calcitonin is no longer a first-line agent for osteoporosis — bisphosphonates and denosumab are preferred — but it retains a role in acute hypercalcemia and Paget's disease management.