Calcitonin
A 32-amino-acid hormone that slows bone breakdown, once a mainstay of osteoporosis treatment and now rarely the right choice
Calcitonin lowers blood calcium by quietening the cells that dissolve bone. The salmon version is what the approved products contain. Its fracture evidence rests on one 1,255-woman trial in which only the middle dose worked; the current label says fracture reduction has not been demonstrated for the injection, and a pooled analysis found more cancers on calcitonin than placebo, so newer drugs have largely replaced it.
What is it?
The thyroid's C cells make calcitonin, which binds receptors on osteoclasts, the cells that dissolve bone, and switches them off. That lowers blood calcium and slows bone turnover. Salmon calcitonin binds the human receptor more tightly than human calcitonin does and lasts longer, which is why the approved products use the fish sequence. After an injection it peaks in about 23 minutes and has a half-life of about an hour, according to the Miacalcin label.
The injection's label now sets narrow terms. It is indicated for symptomatic Paget's disease of bone and for postmenopausal osteoporosis only when alternative treatments are not suitable, and for the early treatment of high blood calcium alongside other drugs. For osteoporosis the label states that fracture reduction efficacy has not been demonstrated, and because of a possible link with cancer it says the need for continued therapy should be re-evaluated periodically.
The fracture evidence rests on one trial. PROOF randomised 1,255 postmenopausal women with osteoporosis to 100, 200 or 400 IU of nasal salmon calcitonin or placebo for five years. The 200 IU dose cut new spine fractures by 33% against placebo (relative risk 0.67), but the 100 and 400 IU doses did not reach significance, which is the awkward part of the result: the middle dose worked and the higher one did not. Only 511 women completed five years.
An oral version was meant to revive it. In the ORACAL phase 3 trial, 565 women took oral recombinant salmon calcitonin, the nasal spray or placebo for 48 weeks: spine bone density rose 1.5% on tablets against 0.78% on the spray and 0.5% on placebo, and the spray did not differ from placebo. Two phase 3 trials of the oral form in knee osteoarthritis found no effect on joint-space narrowing over two years.
Its oldest supportive use is pain after a spinal fracture. In a 1997 placebo-controlled trial in 100 people with recent osteoporotic vertebral crush fractures, 200 IU of nasal calcitonin daily for 28 days relieved spinal pain markedly and got patients out of bed sooner than placebo. Earlier, a two-year pilot in 70 women had found it reduced spinal bone loss and matched oestradiol at the effective dose.
The cancer question is the main reason it fell out of use. The label cites a meta-analysis of 21 randomised trials in which malignancies occurred in 4.1% of people on calcitonin salmon against 2.9% on placebo, and says an increased risk cannot be excluded with long-term injection. A 2016 review, written partly by authors from a company developing an oral calcitonin, concluded the association was weak and a causal link unlikely, but could not rule it out.
Its other risks follow from the molecule: serious allergic reactions, including fatal anaphylaxis, since it is a fish protein (the label suggests skin testing where allergy is suspected); low blood calcium; antibodies that can blunt its effect over time; and a reduced lithium level when the two are combined.
Mechanism of Action
Calcitonin binds the calcitonin receptor on osteoclasts and switches them off, slowing bone breakdown and lowering blood calcium.
Osteoclasts switched off
Binding the calcitonin receptor on bone-dissolving cells slows bone resorption; in PROOF it suppressed a resorption marker by 12 to 14% against placebo.
Lower blood calcium
Less bone breakdown releases less calcium, the basis of its use in hypercalcaemic emergencies and of its hypocalcaemia warning.
Salmon sequence
The fish hormone binds the human receptor more tightly and lasts longer than human calcitonin; being foreign, it can trigger allergy and antibodies.
Short-acting
After an injection it peaks in about 23 minutes and has a half-life of about an hour (label).
Published Research
The studies behind calcitonin, read from their PubMed abstracts: the fracture trial, the oral formulation, pain after spinal fracture, and the cancer question.
PROOF: the fracture trial
1,255 postmenopausal women with osteoporosis took 100, 200 or 400 IU of nasal salmon calcitonin or placebo daily for five years, all with calcium and vitamin D. The 200 IU dose cut new spine fractures by 33% against placebo (relative risk 0.67). The other two doses did not reach significance.
ORACAL: oral calcitonin in 565 women
Over 48 weeks, spine bone density rose 1.5% on oral recombinant salmon calcitonin, 0.78% on the nasal spray and 0.5% on placebo; the spray did not differ from placebo, and about 80% in each group had an adverse event, mostly mild or moderate.
Knee osteoarthritis: two phase 3 trials of oral calcitonin
After 24 months there was no significant effect on joint-space narrowing in either trial; one showed favourable symptom scores that could not be claimed under the trial's testing hierarchy. The authors concluded the formulation gave no reproducible benefit.
Pain after vertebral crush fractures, 100 patients
200 IU of nasal salmon calcitonin daily for 28 days markedly reduced spinal pain and allowed earlier mobilisation than placebo, whose patients stayed mostly in bed despite paracetamol.
Does salmon calcitonin cause cancer? A meta-analysis
A review and updated meta-analysis including oral-formulation data found the association with malignancy weak and causality unlikely, but not excluded; two of the authors were from Tarsa Therapeutics, which was developing oral calcitonin.
Against oestradiol
A two-year randomised pilot in 70 women compared calcitonin with oestradiol as a positive control. Calcitonin reduced spinal bone loss at doses above 250 µg of human calcitonin a week — about 50 IU — and at that dose was as effective as oestradiol.
The oral formulation
A review of salmon calcitonin from 1960 onwards, focused on an oral formulation with greater exposure and efficacy than the nasal one in phase 1 and 2 data. It awaited a phase 3 fracture trial; the oral product did not go on to change practice.
Dosing Data
Miacalcin is injected under the skin or into muscle; the nasal spray was used at 200 IU a day in the fracture trial.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the trials above and the Miacalcin injection prescribing information (Mylan; DailyMed set 26caf31f, version 5, effective September 15, 2024).
Contraindications & Cautions
From the label.
Legal Status
Calcitonin salmon is approved in the US.
Frequently Asked Questions
?What is calcitonin?
A 32-amino-acid hormone from the thyroid's C cells that switches off osteoclasts, the cells that dissolve bone, and so lowers blood calcium.
?Why salmon calcitonin?
The salmon sequence binds the human receptor more tightly and lasts longer than human calcitonin, so every approved product uses it.
?Does it prevent fractures?
One trial says partly. In PROOF, 200 IU nasally cut new spine fractures by 33% over five years, while 100 and 400 IU did not reach significance.
?Why is it used less now?
Newer osteoporosis drugs have stronger fracture evidence, the label says fracture reduction has not been demonstrated for the injection, and a 21-trial meta-analysis found more cancers on calcitonin (4.1%) than placebo (2.9%).
?What is it still used for?
The injection is indicated for symptomatic Paget's disease of bone and osteoporosis when other treatments are not suitable, and for the early treatment of dangerously high blood calcium alongside other drugs.
?Does it help the pain of a spinal fracture?
In a 1997 trial of 100 patients with recent osteoporotic vertebral fractures, nasal calcitonin for 28 days reduced pain and got people moving sooner than placebo.
?Is there an oral form?
Oral salmon calcitonin was tested in phase 3: it raised spine density more than the nasal spray in the ORACAL trial but did not help knee osteoarthritis in two phase 3 trials.
?What dose does the label use?
100 USP units a day by injection for Paget's disease or osteoporosis; for high calcium, 4 units per kg every 12 hours, increased step by step to at most 8 units per kg every 6 hours.
References
- [fda-pi] Miacalcin (calcitonin salmon) injection Prescribing Information. (DailyMed version 5, effective September 15, 2024; read September 30, 2026).
- [other] US FDA, Drugs@FDA (openFDA): calcitonin salmon products, prescription. Read September 30, 2026.
- [pubmed] Chesnut 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." Am J Med, 2000;109(4):267-76. PMID: 10996576.
- [pubmed] Binkley N, et al. "A phase 3 trial of the efficacy and safety of oral recombinant calcitonin: the Oral Calcitonin in Postmenopausal Osteoporosis (ORACAL) trial." J Bone Miner Res, 2012;27(8):1821-9. PMID: 22437792.
- [pubmed] Karsdal MA, et al. "Treatment of symptomatic knee osteoarthritis with oral salmon calcitonin: results from two phase 3 trials." Osteoarthritis Cartilage, 2015;23(4):532-43. PMID: 25582279.
- [pubmed] Lyritis GP, et al. "Pain relief from nasal salmon calcitonin in osteoporotic vertebral crush fractures. A double blind, placebo-controlled clinical study." Acta Orthop Scand Suppl, 1997;275:112-4. PMID: 9385283.
- [pubmed] Wells G, et al. "Does salmon calcitonin cause cancer? A review and meta-analysis." Osteoporos Int, 2016;27(1):13-9. PMID: 26438308.
- [pubmed] MacIntyre I, et al. "Calcitonin for prevention of postmenopausal bone loss." Lancet, 1988;1(8591):900-2. PMID: 2895829.
- [pubmed] Henriksen K, et al. "Oral salmon calcitonin--pharmacology in osteoporosis." Expert Opin Biol Ther, 2010;10(11):1617-29. PMID: 20932224.
Sources & Citations
Studies were read from their PubMed records (October 5, 2026); the label and Drugs@FDA are listed below with their read dates.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.