Calcitonin

Calcitonin is a 32-amino acid peptide hormone naturally produced by the parafollicular C-cells of the thyroid gland. Its primary physiological role is the regulation of calcium homeostasis — calcitonin lowers blood calcium levels by directly inhibiting osteoclast-mediated bone resorption and, to a lesser extent, by increasing renal calcium excretion. Salmon calcitonin, which differs from human calcitonin in 16 of 32 amino acid positions, is approximately 40-50 times more potent than human calcitonin due to higher receptor binding affinity and greater metabolic stability.

The therapeutic form most commonly used is synthetic salmon calcitonin, available as both an injectable (Miacalcin, Calcimar) and a nasal spray (Miacalcin Nasal, Fortical). The drug has been used clinically since the 1970s for the management of postmenopausal osteoporosis, Paget's disease of bone, and hypercalcemia of malignancy.

In osteoporosis, calcitonin produces modest increases in bone mineral density (1-3% over 3-5 years) and has been shown to reduce the risk of vertebral fractures. The PROOF trial demonstrated a 33% reduction in new vertebral fractures with the 200 IU nasal spray dose over 5 years. However, calcitonin's anti-fracture efficacy is generally considered inferior to bisphosphonates, denosumab, and other modern osteoporosis therapies, and it is now typically reserved for patients who cannot tolerate or are not candidates for first-line treatments.

Calcitonin also has a notable analgesic effect on bone pain, particularly the acute pain associated with vertebral compression fractures. This analgesic property, which appears to be mediated by central nervous system mechanisms including endorphin release and serotonin receptor interaction, makes calcitonin uniquely useful in the acute management of painful osteoporotic vertebral fractures.