Calcitonin (salmon) is a synthetic 32-amino-acid peptide hormone (MW ~3431.9 g/mol) identical to calcitonin produced by the ultimobranchial glands of salmon. It is FDA-approved for the treatment of postmenopausal osteoporosis (nasal spray), hypercalcemia of malignancy (injection), and Paget disease of bone (injection). Salmon calcitonin is approximately 40-50 times more potent than human calcitonin at inhibiting osteoclast activity. It is no longer a first-line therapy for osteoporosis due to the availability of more effective agents and a potential cancer risk signal.
Category: Metabolic / Bone Health. Evidence rating: A (strong human clinical data).
Clinical status: FDA-approved (Miacalcin injection 1986; Miacalcin nasal spray 1995; Fortical nasal spray 2005). Used for osteoporosis, Paget disease, and hypercalcemia.
Calcitonin binds to specific calcitonin receptors (CTR, a class B GPCR) on osteoclasts, rapidly inhibiting bone resorption through disruption of the osteoclast ruffled border and reduction of osteoclast motility and number. This leads to decreased serum calcium and reduced bone turnover markers…
Safety considerations: Nasal spray: rhinitis (12%), epistaxis (3.5%), nasal irritation, sinusitis; Injection: nausea (10%), facial flushing (2-5%), injection site reactions, allergic reactions; EMA review (2012) and FDA advisory: meta-analysis of calcitonin trials showed a small increased risk of malignancy (4.1% vs 2.9% placebo). Causal relationship not established but led to restrictions.
Reviewed by the PeptideAtlas Editorial Team. Last reviewed: 2026-08-12.
Calcitonin is no longer a first-line therapy for osteoporosis. Bisphosphonates (alendronate, zoledronic acid), denosumab, and anabolic agents (teriparatide, romosozumab) are preferred due to greater efficacy. Calcitonin may be considered for patients who cannot tolerate other treatments. The EMA withdrew calcitonin nasal spray from the EU market in 2012.
A meta-analysis reviewed by the EMA in 2012 found a small increased incidence of malignancy (4.1% vs 2.9%) in calcitonin-treated patients vs placebo across multiple trials. No single cancer type was identified, and a causal mechanism has not been established. The EMA restricted use; the FDA reviewed the data but did not withdraw calcitonin from the US market.
Salmon calcitonin is approximately 40-50 times more potent than human calcitonin at the calcitonin receptor, likely due to structural differences that enhance receptor binding affinity and resistance to degradation. However, its non-human sequence increases immunogenicity, with up to 60% of patients developing antibodies.
Both are salmon calcitonin nasal sprays delivering 200 IU per spray. Miacalcin (Novartis) was the original brand. Fortical (Upsher-Smith) used recombinant DNA-derived salmon calcitonin rather than synthetic peptide. Generic versions are also available.