How does calcitonin work?

How Calcitonin Works

Mechanism of Action

Calcitonin is a naturally occurring peptide hormone that works primarily by inhibiting osteoclast activity, thereby reducing bone resorption and lowering serum calcium levels. 1

Primary Effects on Bone

• Calcitonin causes rapid, transient inhibition of osteoclasts, the cells responsible for breaking down bone tissue 2
• The hormone binds to calcitonin receptors located on osteoclasts, causing loss of the ruffled border that is essential for bone resorption 1
• This results in decreased osteoclast number and reduced resorptive activity, which can be observed histologically 1
• Single injections produce a marked but temporary suppression of ongoing bone resorption, while prolonged use leads to persistent smaller decreases in bone resorption rates 1

Effects on Calcium Homeostasis

• Calcitonin rapidly lowers serum calcium levels by inhibiting the transfer of calcium from bone to blood 1
• In response to high blood calcium, endogenous calcitonin secretion increases, participating with parathyroid hormone in calcium regulation 1
• The hypocalcemic effect is most pronounced in patients with rapid bone turnover (such as children or those with Paget's disease), while normal adults with slower bone resorption show only slight decreases within normal ranges 1

Additional Mechanisms

• Calcitonin increases renal calcium excretion by decreasing tubular reabsorption of calcium, phosphate, and sodium 1
• There is evidence that calcitonin may augment bone formation through increased osteoblastic activity, though this appears to be an indirect effect mediated through osteoclasts 1, 3
• Recent research suggests calcitonin induces expression of Wnt10b in osteoclasts, which subsequently stimulates osteoblast activity and bone formation 3

Unique Pharmacologic Property

• Calcitonin can uncouple bone turnover, reducing bone resorption without proportionally affecting bone formation, thereby increasing net bone mass 4
• This effect may be dose-dependent, with higher doses potentially inhibiting both resorption and formation 4

Clinical Implications

• The American College of Physicians recognizes calcitonin's efficacy in treating Paget's disease, with effects from a single injection potentially lasting months 5, 6
• Calcitonin provides analgesic effects for osteoporotic bone pain, possibly mediated through β-endorphins and central pain modulation 5, 4
• The hormone also has documented effectiveness in treating bone destruction associated with malignancy and high-turnover osteoporosis 5, 6

Important Caveats

• The biological response plateaus at doses above 400 IU, with no additional benefit from higher doses 1
• Calcitonin's effects are reversible upon discontinuation, as osteoclast activity resumes when the hormone is removed 1
• While effective at increasing trabecular bone mass, the benefit at cortical bone sites is less well-demonstrated 7