{"id":"calcitonin","name":"Calcitonin (salmon)","aliases":["salcatonin","Miacalcin","Miacalcic","salmon calcitonin nasal spray"],"url":"https://lyoresearch.com/compounds/calcitonin","class":{"id":"endocrine-medicines","name":"Bone and endocrine peptide medicines","url":"https://lyoresearch.com/classes/endocrine-medicines"},"summary":"Calcitonin is a thyroid hormone that lowers blood calcium by slowing bone breakdown; the salmon version, more potent than human, was sold for decades as an osteoporosis nasal spray. Its one large fracture trial found a 33% reduction in spinal fractures at the middle dose and none at the higher one. In 2012–2013 European and other regulators withdrew the nasal spray after meta-analyses found a small excess of cancers, leaving short-term injectable use for Paget's disease and hypercalcaemia.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"PROOF RCT (n=1,255, 5 yr) + regulatory meta-analyses","regulatory_status":"Approved (Rx, restricted)","molecule":{"formula":"C145H240N44O48S2","molecular_weight":"3431.9","cas":"47931-85-1","pubchem_cid":16220016,"note":"Salmon calcitonin (salcatonin)"},"pharmacokinetics":{"basis":"label","route":"Subcutaneous or intramuscular injection; nasal spray","half_life":"About 1 hour","licensed_regimen":"Paget's disease and postmenopausal osteoporosis: 100 USP Units daily SC or IM; hypercalcaemia: 4 USP Units/kg every 12 hours, up to 8 USP Units/kg every 6 hours","product":"Miacalcin (calcitonin salmon) injection","source":{"title":"Miacalcin injection prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=26caf31f-7f7c-48a8-a1ac-35d2ceefda2b"}},"outcomes":[{"outcome":"Vertebral fracture risk (osteoporosis, nasal spray)","grade":"A","grade_meaning":"established in humans","effect_size":"small","adverse":false,"human_studies":"1 large RCT (n=1,255, 5 yr)","evidence":"PROOF: the 200 IU dose reduced new vertebral fractures by 33%, but the 100 and 400 IU doses did not — no dose–response, and a trial with 60% dropout. Regulators later judged the benefit marginal.","references":[{"citation":"Chesnut CH 3rd, Silverman S, Andriano K, et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the Prevent Recurrence Of Osteoporotic Fractures study (PROOF).","where":"Am J Med, 2000;109:267–276","url":"https://pubmed.ncbi.nlm.nih.gov/10996576/"}],"verbatim":{"text":"The 200-IU dose of salmon calcitonin nasal spray significantly reduced the risk of new vertebral fractures by 33% compared with placebo [200 IU: 51 of 287, placebo: 70 of 270, relative risk (RR) = 0.67, 95% confidence interval (CI): 0.47- to 0.97, P = 0.03].","citation":"Chesnut CH 3rd, Silverman S, Andriano K, et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the Prevent Recurrence Of Osteoporotic Fractures study (PROOF).","url":"https://pubmed.ncbi.nlm.nih.gov/10996576/"}},{"outcome":"Dose–response","grade":"A","grade_meaning":"established in humans","effect_size":"not measurable","adverse":false,"human_studies":"Same RCT","evidence":"Neither the lower nor the higher dose separated from placebo — the finding that made the 200 IU result hard to trust.","references":[{"citation":"Chesnut CH 3rd, Silverman S, Andriano K, et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the Prevent Recurrence Of Osteoporotic Fractures study (PROOF).","where":"Am J Med, 2000;109:267–276","url":"https://pubmed.ncbi.nlm.nih.gov/10996576/"}],"verbatim":{"text":"The reductions in vertebral fractures in the 100-IU (RR = 0.85, 95% CI: 0.60- to 1.21) and the 400-IU (RR = 0.84, 95% CI: 0.59- to 1.18) groups were not significantly different from placebo.","citation":"Chesnut CH 3rd, Silverman S, Andriano K, et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the Prevent Recurrence Of Osteoporotic Fractures study (PROOF).","url":"https://pubmed.ncbi.nlm.nih.gov/10996576/"}},{"outcome":"Cancer risk (long-term use)","grade":"B","grade_meaning":"probable, not settled","effect_size":"small","adverse":true,"human_studies":"Regulatory meta-analyses of RCTs","evidence":"The EMA's 2012 review of randomised trials found a higher proportion of cancers in people on calcitonin than on placebo (about 2.4% excess for the nasal spray over long-term use). The signal is small and the mechanism unknown, but it was enough to end chronic use.","references":[{"citation":"European Medicines Agency. European Medicines Agency recommends limiting long-term use of calcitonin medicines (press release, 20 July 2012).","where":"EMA","url":"https://www.ema.europa.eu/en/news/european-medicines-agency-recommends-limiting-long-term-use-calcitonin-medicines"}]},{"outcome":"Paget's disease and acute hypercalcaemia","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"Decades of use; older trials","evidence":"Injectable calcitonin still has short-term licences for Paget's disease, acute bone loss from immobilisation and hypercalcaemia of malignancy, where bisphosphonates have largely replaced it.","references":[{"citation":"European Medicines Agency. European Medicines Agency recommends limiting long-term use of calcitonin medicines (press release, 20 July 2012).","where":"EMA","url":"https://www.ema.europa.eu/en/news/european-medicines-agency-recommends-limiting-long-term-use-calcitonin-medicines"}]}],"regions":[{"region":"European Union","status":"Restricted","note":"Nasal spray marketing authorisations withdrawn following the EMA's July 2012 review; injectable use limited to short courses for Paget's disease, acute immobilisation bone loss and hypercalcaemia of malignancy."},{"region":"United States","status":"Approved, prescription-only","note":"Miacalcin injection and nasal spray remain approved; an FDA advisory committee voted in March 2013 that the nasal spray's benefit for osteoporosis did not outweigh the cancer risk, and the label carries a malignancy warning."},{"region":"United Kingdom","status":"Restricted","note":"Nasal spray withdrawn in 2012 in line with the EMA decision; injection retained for short-term indications."},{"region":"Australia","status":"Restricted","note":"Nasal spray products for osteoporosis were withdrawn; injectable use restricted."},{"region":"Canada","status":"Restricted","note":"Health Canada withdrew nasal calcitonin for osteoporosis in 2013."},{"region":"Sport (WADA)","status":"Not prohibited","note":"Not on the Prohibited List."}],"faq":[{"q":"Why was calcitonin nasal spray withdrawn?","a":"A regulatory meta-analysis of randomised trials found more cancers in people on calcitonin than on placebo, and the fracture benefit for osteoporosis was small and inconsistent. The EMA judged the balance unfavourable for long-term use in 2012."},{"q":"Is calcitonin still used?","a":"Yes, short-term by injection — for Paget's disease, hypercalcaemia and acute bone loss from immobilisation — and in the US the nasal spray is still sold with a warning."},{"q":"Is calcitonin a peptide?","a":"Yes — 32 amino acids with a disulfide ring at one end. The salmon version is the medicine because it is far more potent than human calcitonin."}],"references":[{"cite":"Chesnut CH 3rd, Silverman S, Andriano K, et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the Prevent Recurrence Of Osteoporotic Fractures study (PROOF).","where":"Am J Med, 2000;109:267–276","url":"https://pubmed.ncbi.nlm.nih.gov/10996576/","note":"1,255 women, 5 years; 511 completed."},{"cite":"European Medicines Agency. European Medicines Agency recommends limiting long-term use of calcitonin medicines (press release, 20 July 2012).","where":"EMA","url":"https://www.ema.europa.eu/en/news/european-medicines-agency-recommends-limiting-long-term-use-calcitonin-medicines","note":"Withdrawal of the nasal spray; cancer signal from pooled trials."}],"last_reviewed":"2026-09-23","literature_searched_to":"2026-09-23","changelog":[{"date":"2026-09-23","note":"Initial publication. Grade A on certainty; small, inconsistent osteoporosis effect and the 2012 withdrawal recorded."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"}