Calcitonin (Miacalcin / Fortical)

Written by The Peptide Record editorialClinical review not yet completedLast reviewed 12 September 2026

Salmon calcitonin is a genuinely old, once-mainstream osteoporosis and Paget's disease drug — and a real case study in how a modest, uneven efficacy profile plus a real safety signal can quietly shrink a drug's role without a formal withdrawal. Its largest dedicated fracture trial found a significant benefit at only one of three tested doses. Separately, a 2013 FDA review of pooled trial data (10,883 patients across 21 trials) found a higher malignancy rate in calcitonin-treated patients (4.1%) than placebo (2.9%) — FDA didn't pull the drug, and updated the label in 2014 rather than adding a boxed warning, but it's used far less today, and for good reason.

In brief

Should you care? Yes as a cautionary contrast to this site's teriparatide and abaloparatide pages — calcitonin is the older bone-drug case where the safety picture, not a lack of any effect, is what narrowed its real-world use.

The short version

Approved for decades for postmenopausal osteoporosis, Paget's disease, and hypercalcemia.
Its largest dedicated fracture trial (PROOF, 1,255 patients) found a significant benefit at only one of three tested doses.
A 2013 FDA review of pooled trial data (10,883 patients, 21 trials) found malignancies in 4.1% of calcitonin-treated patients versus 2.9% of placebo patients — a real, unresolved signal that led to a 2014 label update.

What it is, and its real approvals

Calcitonin is a 32-amino-acid peptide hormone, normally secreted by the thyroid's C-cells, that inhibits osteoclast-driven bone resorption. Synthetic salmon calcitonin (more potent and longer-acting in humans than the human hormone itself) has been FDA-approved for decades under brand names including Miacalcin (injection and nasal spray) and Fortical (recombinant nasal spray), plus generics, for postmenopausal osteoporosis, Paget's disease of bone, and hypercalcemia of malignancy.

The PROOF fracture trial, and its oddity

The main dedicated fracture trial (Chesnut et al., "the PROOF study," Am J Med 2000;109(4):267-276, PMID 10996576) randomized 1,255 postmenopausal women with established osteoporosis to nasal calcitonin at 100, 200, or 400 IU/day, or placebo, over 5 years. Only the 200 IU/day dose showed a statistically significant reduction in new vertebral fractures versus placebo — the 100 IU and 400 IU doses did not reach significance, an unusual, non-dose-dependent pattern that drew scrutiny well before 2013. No dose showed a significant reduction in nonvertebral fractures.

The 2013 cancer-signal review

In March 2013, a joint FDA advisory committee (Reproductive Health Drugs and Drug Safety and Risk Management) reviewed a pooled meta-analysis of 21 randomized trials of calcitonin-salmon (nasal and investigational oral formulations), covering 10,883 patients (6,151 calcitonin, 4,732 placebo). Malignancies were reported in 254 of 6,151 (4.1%) calcitonin-treated patients versus 137 of 4,732 (2.9%) placebo-treated patients. In March 2014, US prescribing information for all salmon calcitonin products was revised to note this meta-analysis "suggests an increased risk of malignancies in calcitonin-salmon-treated patients compared to placebo" — real, honest regulatory language for a genuine, unresolved signal, though FDA did not add a boxed warning.

Neither a clean exoneration nor a withdrawal

FDA's 2013-2014 conclusion was that the pooled data did not establish a confirmed causal relationship, but that the benefit-risk balance should be considered carefully for each patient — a real, unresolved signal stated plainly on the label, not a rare idiosyncratic footnote.

Where it sits today

Calcitonin was never withdrawn and remains an approved option, but current osteoporosis treatment guidelines generally place it well behind bisphosphonates, denosumab, and the anabolic PTH-analog drugs (teriparatide, abaloparatide) covered elsewhere on this site — both because its fracture-reduction evidence is thinner and because of the unresolved 2013 cancer signal. It still has a real, narrower role: acute pain relief after an osteoporotic vertebral fracture, and Paget's disease management where other drugs aren't tolerated.

References

Chesnut CH 3rd, Silverman S, Andriano K, et al., "A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study," Am J Med 2000;109(4):267-276, PMID 10996576.
FDA joint meeting of the Reproductive Health Drugs and Drug Safety and Risk Management Advisory Committees, 5 March 2013 — pooled meta-analysis of 21 calcitonin-salmon trials (10,883 patients), malignancies in 4.1% (calcitonin) vs. 2.9% (placebo).
FDA-mandated label revision for all salmon calcitonin products, March 2014.