Calcitonin (Salmon)

A synthetic 32-amino-acid copy of salmon calcitonin, FDA approved as an injection for Paget's disease of bone, hypercalcemia, and postmenopausal osteoporosis and as a nasal spray for osteoporosis, that suppresses osteoclast activity through the calcitonin receptor.

Also referenced as: Salmon calcitonin, Calcitonin-salmon, Synthetic salmon calcitonin, sCT, Salcatonin, Miacalcin, Miacalcic, Fortical, Calcimar, Calsynar, Recombinant salmon calcitonin, rsCT, TBRIA, Calcitonin salmon nasal spray

Also appears in: Longevity

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What is Calcitonin (Salmon)?

Calcitonin (salmon) is a synthetic 32-amino-acid polypeptide with the same linear sequence as the calcitonin secreted by salmon ultimobranchial cells. It is a true peptide hormone analog, not a derivative of human calcitonin: the fish sequence differs from the human one at half of its 32 positions, and the approved labeling describes its actions as essentially identical to mammalian calcitonins but with greater potency per milligram and a longer duration of action. Older British and European labeling calls it salcatonin, a former British Approved Name; in the U.S. it is labeled calcitonin-salmon.

It has been an FDA-approved drug for decades. Injectable salmon calcitonin has been on the U.S. market since the 1970s under the brand Calcimar (two Sanofi-lineage NDAs, 017497 and 017769, the latter a solution for injection approved in April 1978; both are now discontinued), and was approved again in July 1986 as Miacalcin (NDA 017808), which remains marketed alongside several generic injections. A nasal spray followed in August 1995 (Miacalcin Nasal Spray, NDA 020313) and a second nasal product in August 2005 (Fortical, NDA 021406). Both nasal brands have since been discontinued and the nasal format survives in the U.S. only as generics. The compound appears in the research-peptide market under its generic name, usually as lyophilized powder, where it draws interest from people reading about bone density and the broader framing of skeletal aging rather than from any current clinical momentum.

How it works

Calcitonin-salmon is an agonist of the calcitonin receptor (CTR), a class B G-protein-coupled receptor in the same family as the PTH and GLP-1 receptors. Its labeled pharmacology is dominated by bone, with recognized direct effects on the kidney and gut:

• Rapid osteoclast inhibition — calcitonin causes isolated osteoclasts to stop their ruffling, motile activity within minutes and then to retract their cytoplasmic processes and fall quiescent, a direct and reversible effect that underlies the fall in bone resorption seen clinically (Chambers and Magnus, Journal of Pathology, 1982, 136(1):27–39). The injection label reports that in hypercalcemia a reduction in serum calcium is evident within 1 to 2 hours of a dose, consistent with this fast cellular action.
• Receptor engagement and the potency difference — the first full-length cryo-EM structure of a class B GPCR–G-protein complex was the human calcitonin receptor bound to salmon calcitonin and heterotrimeric Gs, showing the peptide seated in an extended hydrophobic pocket opened by outward movement of the extracellular ends of helices 6 and 7 (Liang et al., Nature, 2017, 546(7656):118–123). Structure–activity work attributes the higher potency and longer action of the salmon sequence relative to human calcitonin to its more stable leucine-based amphipathic alpha-helix (Andreotti et al., Journal of Biological Chemistry, 2006, 281(34):24193–24203).
• Homologous receptor downregulation (“escape”) — exposure of human osteoclast-like cells to calcitonin suppresses calcitonin receptor mRNA, and expression recovers when the hormone is withdrawn (Takahashi et al., Journal of Clinical Investigation, 1995, 95(1):167–171). This is the leading explanation for the loss of effect seen with continuous dosing, and it is one reason intermittent or short courses were historically preferred for Paget’s disease.
• Renal calcium excretion and analgesia — the label notes direct renal effects that increase calcium excretion, contributing to the hypercalcemia indication. A separate, less well understood analgesic action has been reported repeatedly in acute osteoporotic vertebral fracture, including a double-blind placebo-controlled study of 100 IU daily by injection in 56 hospitalized patients (Lyritis et al., Calcified Tissue International, 1991, 49(6):369–372); the mechanism is not established and is not part of any approved indication.

Research status

Calcitonin-salmon has a long approval record, a fracture trial that regulators ultimately judged insufficient, a formal malignancy signal, and a failed oral-formulation program. Its osteoporosis role is largely superseded.

Approved indications and their evidence. The injection is approved for symptomatic Paget’s disease of bone in patients for whom alternative treatments are not suitable, for early treatment of hypercalcemic emergencies, and for postmenopausal osteoporosis in women more than 5 years postmenopause when alternative treatments are not suitable. The Paget’s evidence comes from open-label trials with historical controls in which biochemical markers improved by more than 30% in roughly two-thirds of patients; the hypercalcemia evidence comes from four open-label trials in 53 patients with an average 8-hour serum calcium reduction of about 9% (2 to 3 mg/dL). The osteoporosis section of the injection label rests on total body calcium gains in two small randomized, open-label 2-year studies (34 treated, 35 control), with new vertebral fracture counts of 6 versus 5 in year one and 7 versus 7 in year two, and notes that a controlled fracture study was discontinued early without showing benefit. The nasal spray label reports two 2-year placebo-controlled trials in which lumbar spine BMD rose 1.56% versus 0.20% (with calcium supplementation) and 1.02% versus −1.85% (without), with no effect demonstrated on forearm or hip cortical bone. Both current labels carry the statement that fracture reduction efficacy has not been demonstrated.

PROOF (Chesnut et al., American Journal of Medicine, 2000, 109(4):267–276). The Prevent Recurrence of Osteoporotic Fractures study randomized 1,255 postmenopausal women with established osteoporosis to nasal salmon calcitonin 100, 200, or 400 IU daily or placebo for 5 years. The 200 IU dose reduced new vertebral fractures by 33% (51 of 287 versus 70 of 270; RR 0.67, 95% CI 0.47–0.97, P = 0.03), but the 100 IU (RR 0.85) and 400 IU (RR 0.84) arms did not differ from placebo, lumbar spine BMD rose only 1% to 1.5%, and only 511 of 1,255 participants completed 5 years. The absence of a dose–response relationship, the high dropout rate, and the small BMD effect are the reasons this result never earned a fracture-reduction claim on the U.S. label.

The malignancy signal and its regulatory consequences. A meta-analysis of 21 randomized controlled trials totaling 10,883 patients, reported in the current labels, found malignancies in 4.1% of calcitonin-treated patients (254 of 6,151) versus 2.9% of placebo patients (137 of 4,732); in the 18 nasal-spray trials the figures were 4.5% (122 of 2,712) versus 2.3% (30 of 1,309), a risk difference of 1.4% (95% CI 0.3–2.6). The labels state that a definitive causal relationship cannot be established and that the need for continued therapy should be re-evaluated periodically. On 20 July 2012 the EMA’s CHMP concluded that the cancer risk in long-term trials was 0.7% to 2.4% higher than placebo, highest in intranasal trials, that the benefit–risk balance for postmenopausal osteoporosis was no longer positive, and that the nasal formulation, used only for osteoporosis, should be withdrawn; injectable calcitonin was retained for short courses in Paget’s disease (second line), acute immobilization bone loss, and cancer-related hypercalcemia. Health Canada announced in July 2013 that calcitonin nasal sprays would be withdrawn from the Canadian market, effective October 2013. In the U.S., a joint meeting of the Reproductive Health Drugs and Drug Safety and Risk Management advisory committees on March 5, 2013 recommended against continued marketing of the nasal spray for osteoporosis and advised that any new calcitonin-salmon product would need to show fracture reduction. The FDA did not withdraw the products; instead, labeling supplements approved in March 2014 (Miacalcin injection and nasal spray) and July 2014 (Fortical) narrowed the osteoporosis indication to women more than 5 years postmenopause when alternatives are not suitable, added the fracture-efficacy disclaimer, and inserted the malignancy warning. A sponsor-linked re-analysis later argued that the association is weak and causality unlikely, while acknowledging that an association cannot be excluded (Wells et al., Osteoporosis International, 2016, 27(1):13–19); two of its four authors were employees of the company developing the oral tablet.

ORACAL and the oral program — a failure to reach approval (NCT00959764). The Oral Calcitonin in Postmenopausal Osteoporosis trial randomized 565 women (4:3:2) to an oral recombinant salmon calcitonin tablet (0.2 mg daily), nasal synthetic salmon calcitonin 200 IU daily, or placebo for 48 weeks. Lumbar spine BMD rose 1.5% on the tablet versus 0.78% on nasal spray and 0.5% on placebo; the nasal spray did not separate from placebo on the primary endpoint, and gastrointestinal adverse events were reported by nearly half of women in every group (Binkley et al., Journal of Bone and Mineral Research, 2012, 27(8):1821–1829). Tarsa Therapeutics submitted the tablet to the FDA in 2015 under the proposed name TBRIA and the application was accepted for filing. No approval followed: Drugs@FDA lists no oral calcitonin product, and the program never reached the market. Secondary literature occasionally describes TBRIA as approved; it is not. The outcome is consistent with the 2013 committee’s position that a bone-density endpoint is no longer sufficient for a calcitonin osteoporosis approval.

Current work. No new indication has been approved in 2025 or 2026; the label versions published in July 2025 and June 2026 for the injection and July 2026 for the generic nasal spray contain no new major changes. ClinicalTrials.gov currently lists small investigator-initiated studies of calcitonin-salmon as an analgesic or adjunct (neuropathic pain after spinal cord injury, NCT05805683; acute herpes zoster, NCT07655804; an adjunct to bupivacaine in a transversalis fascia plane block for cesarean section, NCT07033104) and a Phase 4 study using calcitonin pretreatment to improve sestamibi SPECT-CT imaging in primary hyperparathyroidism (NCT03935984). There is no registered osteoporosis, anti-aging, or longevity trial. The molecule’s most active scientific legacy is indirect: engineered dual amylin and calcitonin receptor agonists (DACRAs) derived from the salmon calcitonin sequence are in clinical development for obesity and osteoarthritis (Gydesen et al., British Journal of Pharmacology, 2017, 174(7):591–602; KBP-336, Phase 2 in obese adults with knee osteoarthritis, NCT06833749), but those are distinct molecules with different pharmacology.

Common dosage forms

• Injection (approved) — Miacalcin injection and several generics are supplied as a sterile solution of 200 USP units/mL in a 2 mL multi-dose vial (400 units per vial), for intramuscular or subcutaneous use, stored refrigerated. Historical products were also supplied at 100 units/mL. Potency is expressed in international or USP units rather than mass.
• Nasal spray (approved, generic only in the U.S.) — a metered 3.7 mL bottle of 2,200 IU/mL delivering 200 IU per 0.09 mL actuation, 30 doses per bottle. The Miacalcin and Fortical brands are discontinued; the format was withdrawn entirely in the EU and Canada.
• Oral delayed-release tablet (never approved) — a 0.2 mg recombinant salmon calcitonin tablet reached Phase 3 and an FDA filing but is not a marketed format anywhere.
• Research supply — lyophilized calcitonin-salmon acetate powder in vials, conventionally labeled in micrograms or milligrams rather than units. Unit labeling of the approved products reflects biological potency assays and does not translate one-to-one to the mass labeling of uncharacterized material.

Key considerations

• The approval is real, but the osteoporosis indication is a historical remnant. FDA Approved status reflects the existence of approved drug products; it does not mean calcitonin-salmon is a current standard of care for bone loss. Both U.S. labels confine the osteoporosis indication to women more than 5 years postmenopause when alternatives are unsuitable and state that fracture reduction has not been demonstrated, the EU withdrew the indication outright in 2012, and Canada withdrew the nasal sprays in 2013. Bisphosphonates, denosumab, and the PTH1R agonists displaced it on efficacy grounds well before the safety review.
• A malignancy signal is on the label. The 21-trial meta-analysis (4.1% versus 2.9% malignancy; 4.5% versus 2.3% in nasal trials) is reproduced in the U.S. labeling, which advises periodic re-evaluation of continued therapy. Causality has not been established and has been argued against, but the signal was sufficient for two regulators to remove the osteoporosis use and for FDA to narrow it. Nothing in the record supports open-ended or wellness-framed use.
• Hypersensitivity, hypocalcemia, and antibody formation are labeled risks. Serious hypersensitivity reactions including anaphylaxis with death have been reported with the injectable; skin testing is suggested where hypersensitivity is suspected. Tetany and seizures from hypocalcemia have been reported, and hypocalcemia must be corrected before treatment. Circulating anti-salmon-calcitonin antibodies develop with chronic use: the nasal label reports a measurable titer in 69% of treated patients versus 3% on placebo in a two-year study, and the injection label reports antibodies in about half of Paget’s patients tested after 2 to 18 months; high titers are the labeled explanation for secondary loss of response.
• The nasal and injectable products are not pharmacokinetically interchangeable. Nasal bioavailability is 3% to 5% relative to intramuscular dosing, with a terminal half-life of roughly 18 minutes, versus about 58 minutes for intramuscular and 59 to 64 minutes for subcutaneous injection. Nasal adverse effects (rhinitis, irritation, erythema, excoriation) are more frequent in people 65 and older.
• Naming can mislead. “Calcitonin” alone may refer to human calcitonin, which is not an approved U.S. drug, or to calcitonin gene-related peptide (CGRP), a different neuropeptide from the same gene whose antagonists are migraine drugs. “Calcitonin salmon” is a specific molecule and an inhibitor of bone resorption; it is not an anabolic agent like teriparatide or abaloparatide, and it is not a DACRA.