Calcitonin (salmon)

Salmon calcitonin is a 32-amino-acid peptide hormone with a disulfide-bridged ring and C-terminal prolinamide that inhibits osteoclast bone resorption. It is FDA-approved as Miacalcin for conditions including Paget's disease of bone and hypercalcemia.

Last reviewed 2026-10-25 by the PeptideWiki editorial team. Editorial policy.

Overview

Calcitonin is a peptide hormone produced in mammals mainly by the parafollicular C cells of the thyroid, and in fish by the ultimobranchial gland. It lowers blood calcium by inhibiting osteoclast-mediated bone resorption and by effects on the kidney. Calcitonins from different species differ in sequence, and salmon calcitonin was found to be considerably more potent in humans than human calcitonin, partly because of greater receptor affinity and slower clearance. This made salmon calcitonin the form most widely used as a drug.

Salmon calcitonin is marketed in the United States as Miacalcin, originally as an injection and also as a nasal spray. Its uses have included Paget's disease of bone, hypercalcemia and postmenopausal osteoporosis. In the 2010s, regulatory reviews in Europe and the United States examined data suggesting a small increase in malignancy with long-term use, and regulators restricted or reconsidered some indications as a result. Its role in osteoporosis has declined as other agents became available.

Structure

Salmon calcitonin is a 32-residue peptide with the sequence Cys-Ser-Asn-Leu-Ser-Thr-Cys-Val-Leu-Gly-Lys-Leu-Ser-Gln-Glu-Leu-His-Lys-Leu-Gln-Thr-Tyr-Pro-Arg-Thr-Asn-Thr-Gly-Ser-Gly-Thr-Pro-NH2 (CSNLSTCVLGKLSQELHKLQTYPRTNTGSGTP-NH2). A disulfide bond between Cys1 and Cys7 forms an N-terminal ring, and the C-terminus is a prolinamide; both features are required for full activity. The central region forms an amphipathic helix. Salmon calcitonin differs from human calcitonin at many positions. Drug substance is generally made synthetically and supplied as an acetate salt.

Mechanism

Calcitonin binds the calcitonin receptor, a class B G protein-coupled receptor highly expressed on osteoclasts, signaling through cyclic AMP and other pathways. Activation rapidly reduces osteoclast activity and bone resorption, lowering serum calcium, and also increases renal calcium excretion. When the calcitonin receptor associates with receptor activity-modifying proteins (RAMPs), it forms amylin receptors, and salmon calcitonin also activates these. This overlap explains the interest in dual amylin and calcitonin receptor agonists in metabolic research. With continuous exposure, responses can diminish, a phenomenon called escape.

Research

Paget's disease and hypercalcemia

Salmon calcitonin was among the first effective treatments for Paget's disease of bone, reducing markers of bone turnover, and it has been used for the rapid but modest lowering of serum calcium in hypercalcemia. In both settings, bisphosphonates and other agents now often play a larger role, but calcitonin's fast onset has kept it in some treatment approaches. Current labeling and guidelines determine its present place.

Osteoporosis

Clinical trials of nasal and injectable salmon calcitonin in postmenopausal osteoporosis reported reductions in vertebral fracture risk in some analyses, though effects on bone density were smaller than with other agents, and evidence for nonvertebral fracture reduction was limited. Oral formulations were developed and tested in phase 3 trials, with mixed results. Combined with the malignancy findings, this has reduced its use in osteoporosis.

Malignancy signal

Pooled analyses of randomized trials, reviewed by European and US regulators in the early 2010s, suggested a small increase in malignancies among people treated long term with calcitonin compared with placebo. A causal relationship was not established, but regulators restricted long-term use in some regions and reassessed indications. This history is an important consideration when interpreting the older clinical literature.

Pain and amylin-receptor research

Calcitonin has been studied for analgesic effects in acute vertebral fracture pain and other conditions, with small trials reporting reduced pain, though mechanisms are uncertain. Separately, the recognition that salmon calcitonin activates amylin receptors informed the design of dual amylin and calcitonin receptor agonists, such as cagrilintide, studied in obesity. These lines of research extend beyond its bone indications. The analgesic findings are not consistent across studies and are not an established basis for clinical use.

Regulatory status

Salmon calcitonin is FDA-approved and marketed as Miacalcin, as an injection and nasal spray; approved indications have included Paget's disease of bone, hypercalcemia and postmenopausal osteoporosis, but labeling and its use have changed following regulatory review of a possible malignancy risk with long-term treatment, so check current labeling. It is approved in many other countries, with restrictions varying by jurisdiction. For sport, check the current WADA Prohibited List.

Status changes often. See the regulatory tracker for dated updates.

Quality and identity testing

A certificate of analysis should confirm identity by mass spectrometry, with the observed mass matching the expected mass shown on this page for the disulfide-bonded, C-terminally amidated peptide, and report HPLC purity with the chromatogram. Compound-specific checks include complete Cys1-Cys7 disulfide formation (the reduced form is 2 Da heavier), absence of disulfide-linked dimers, presence of the C-terminal amide rather than free acid, and deamidation of asparagine and glutamine residues. Pharmacopeial monographs for salmon calcitonin set specific related-substance limits. The acetate content and net peptide content should be stated, and identity confirmed as salmon rather than human calcitonin.

Open Calcitonin (salmon) in the sequence analyzer to see the expected [M+H]⁺ and multiply charged ions for an MS identity check (set the N-acetyl, amide and disulfide options to match).

For a walkthrough of each section of a certificate, see how to read a COA.

Storage and stability

Store lyophilized salmon calcitonin sealed at -20 °C or in refrigerated conditions as indicated on its documentation, protected from light and moisture, and warm vials before opening. Pharmaceutical injection and nasal products have their own refrigeration and in-use instructions. The disulfide ring can be disrupted by reducing agents, and the amphipathic helix can promote aggregation and fibril formation at high concentration or with agitation. Prepare research solutions in slightly acidic sterile buffer, keep them cold, aliquot, and avoid repeated freeze-thaw cycles.

Download the Calcitonin (salmon) data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.

Latest research

Frequently asked questions

Related compounds

• Teriparatide

  Teriparatide is the N-terminal 34-amino-acid fragment of human parathyroid hormone, PTH(1-34). It is an FDA-approved bone-forming (anabolic) agent, marketed as Forteo, used for osteoporosis in people at high risk of fracture.

• Abaloparatide

  Abaloparatide is a synthetic 34-amino-acid analogue of parathyroid hormone-related protein, PTHrP(1-34). It is an FDA-approved anabolic agent for osteoporosis, marketed as Tymlos, that acts on the PTH type 1 receptor.

• Cagrilintide

  Cagrilintide is an investigational long-acting acylated analogue of amylin, a pancreatic hormone involved in satiety. It has been studied alone and in combination with semaglutide (CagriSema) for weight management.

• Pramlintide

  Pramlintide is a synthetic analogue of the pancreatic hormone amylin, modified with three proline substitutions to prevent aggregation. It is FDA-approved as Symlin for use with mealtime insulin in type 1 and type 2 diabetes.

References

1. PubMed: all indexed literature on Calcitonin (salmon)
2. ClinicalTrials.gov: registered studies mentioning Calcitonin (salmon)