Calcitonin-salmon

Calcitonin receptors are found on osteoclasts, the cells that break down bone. After an injection, bone resorption drops sharply at first; with continued use the reduction becomes smaller but persists, and bone tissue shows fewer osteoclasts with less resorbing activity¹. Because less calcium is released from bone, blood calcium falls, modestly in healthy adults and more noticeably in people with rapid bone turnover¹.

In the kidney it increases excretion of calcium, phosphate and sodium by reducing their reabsorption, and short-term studies show transient drops in stomach acid and pancreatic secretions¹. Together these effects explain its use in Paget's disease of bone and in high blood calcium.

The largest fracture trial, PROOF, randomized 1,255 postmenopausal women with osteoporosis to the nasal spray at one of three strengths or to placebo for five years³. The middle strength reduced new spine fractures by about a third, but the lower and higher strengths did not differ significantly from placebo, fewer than half of participants completed five years, and spine bone density rose only slightly³. Current US labels state that fracture-reduction efficacy has not been demonstrated^1,2. US labels cite a meta-analysis of 21 clinical trials suggesting a higher overall cancer risk in people treated with calcitonin-salmon¹, and a 2012 European review found evidence of a small increased cancer risk with long-term use⁴.

A later meta-analysis, co-written by authors from a company developing an oral calcitonin, judged a causal link unlikely while acknowledging that an association could not be excluded⁵.

FDA-approved for symptomatic Paget's disease of bone, hypercalcemia and postmenopausal osteoporosis (injection), and for osteoporosis in women more than five years past menopause (nasal spray), with Paget's disease and osteoporosis limited to cases where other treatments are not suitable^1,2.

In 2012 the European Medicines Agency concluded that its benefits did not outweigh its risks in osteoporosis, ended that use, and limited its remaining uses to short-term treatment⁴.

Labels list nausea with or without vomiting, injection-site inflammation and flushing for the injection, and rhinitis, nosebleeds and other nasal symptoms, back pain, joint pain and headache for the spray, which can also cause nasal ulceration^1,2. Warnings cover serious allergic reactions including fatal anaphylaxis, low blood calcium, a possible increase in cancer risk, and antibodies that can reduce response over time^1,2.

1. FDA label: Miacalcin injectionFDA label (DailyMed)
2. FDA label: Calcitonin salmon nasal spray (Apotex)FDA label (DailyMed)
3. Chesnut et al., Am J Med 2000PubMed
4. EMA: Calcitonin referral (2012)European Medicines Agency
5. Wells et al., Osteoporos Int 2016PubMed