Peptides›Metabolic›Calcitonin (salmon)

Calcitonin (salmon)

/ Synthetic salmon calcitonin analog (32-residue peptide)

TIER 1 · ClinicalN = 0 · TESTING PENDINGMW 3431.90 g·mol⁻¹

ALIAS · Miacalcin (trade) · Fortical (trade — nasal spray) · Salcatonin · Salmon calcitonin

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Research use onlyAny dose figures below describe what specific cited studies used, reported factually. Nothing on this page is guidance for human use.READ FIRST →

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§ A · Identity

Primary sequenceCSNLSTCVLGKLSQELHKLQTYPRTNTGSGTP-NH2 (disulfide between Cys1 and Cys7)

MW · 3431.90CLASS · Synthetic salmon calcitonin analog (32-residue peptide)CATEGORY · Metabolic

Tier 1. Salmon calcitonin is FDA-approved for Paget disease of bone, hypercalcemia, and postmenopausal osteoporosis. The synthetic 32-residue peptide has higher receptor affinity and longer duration of action than human calcitonin and has been in clinical use since the 1970s. The PROOF trial (Chesnut 2000) supported the postmenopausal-osteoporosis indication via a vertebral fracture endpoint.

§ B · Mechanism of action

Salmon calcitonin is a synthetic 32-residue peptide analog of the endogenous parafollicular thyroid C-cell hormone, with the salmon sequence preferred over the human form due to higher binding affinity at the human calcitonin receptor and slower metabolic clearance. Receptor activation on osteoclasts inhibits bone resorption directly, producing a rapid fall in serum calcium in hypercalcemic states and a more gradual reduction in bone turnover with chronic administration. Secondary central nervous system effects, including a putative analgesic action in vertebral fracture pain, have been described in some clinical literature.

§ C · Human clinical evidence

Tier 1. The PROOF trial (Chesnut and colleagues, American Journal of Medicine 2000) randomised approximately 1,255 postmenopausal women with osteoporosis to nasal salmon calcitonin or placebo over five years and reported a reduction in new vertebral fracture incidence at the 200 IU dose, the basis for the postmenopausal-osteoporosis indication. Earlier intramuscular and subcutaneous use in Paget disease and hypercalcemia of malignancy is supported by older controlled trials. Subsequent comparative-effectiveness data have generally favoured bisphosphonates and other antiresorptives over calcitonin for osteoporosis fracture prevention.

§ D · Primary literature

PubMed10996576Chesnut CH 3rd et al. — A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group · The American Journal of Medicine · human-phase-3-rctFive years of intranasal salmon calcitonin 200 IU/day was associated with a 33% reduction in new vertebral fracture incidence versus placebo in postmenopausal women with osteoporosis; 100 IU and 400 IU doses did not reach significance.Limitations: Single pivotal trial; high dropout; non-vertebral fracture and hip fracture endpoints not significant; dose-response inverted-U pattern unexplained.2000

PubMed24259626Overman RA et al. — Salmon calcitonin use and associated cancer risk · The Annals of Pharmacotherapy · meta-analysisPooled analysis of long-term salmon calcitonin randomised trials identified a small but statistically detectable excess of malignancies in calcitonin-treated participants compared with placebo, the basis for the FDA ODAC review and the subsequent EMA label restriction.Limitations: Heterogeneity across pooled trials; cancer endpoints not pre-specified in most contributing studies; absolute event rates small.2013

§ F · Safety signal

The 2014 FDA Oncologic Drugs Advisory Committee (ODAC) review aggregated long-term salmon calcitonin trials and identified a small numerical excess of malignancies in calcitonin-treated participants compared with placebo across pooled trials. The European Medicines Agency subsequently restricted nasal calcitonin use, removing the postmenopausal-osteoporosis indication in the EU and limiting use to short-term Paget disease and hypercalcemia indications. The FDA retained US approval but updated labelling. Common adverse events include nasal irritation (intranasal route), flushing, nausea, and injection-site reactions (parenteral route).

§ H · Regulatory status

Regulatory status

FDA status:: FDA-approved
Compounding:: Not eligible for compounding (approved, not in shortage)

§ I · Notable gaps and controversies

The cancer-signal review is a load-bearing fact for this molecule: an aggregate signal across many trials of modest individual size is statistically fragile but clinically consequential. The EU restriction and US label update reflect different regulatory tolerances applied to the same dataset. Salmon calcitonin's role in osteoporosis has substantially diminished in favour of bisphosphonates, denosumab, and anabolic agents; current use concentrates in Paget disease and acute hypercalcemia.