Calcitonin Salmon (Miacalcin, Fortical)
Calcitonin Salmon (Synthetic), also known as Salmon Calcitonin (sCT); USP designation: Calcitonin-salmon
FDA-approved synthetic 32-amino-acid polypeptide identical to salmon calcitonin, used for postmenopausal osteoporosis, Paget's disease, and hypercalcemia. Intranasal 200 IU reduced new vertebral fractures by 33% versus placebo in the PROOF trial (N=1255; PMID 10996576). Well-documented analgesic properties for vertebral compression fracture pain. Considered second-line due to modest efficacy versus newer agents and a cancer risk signal with long-term use (FDA Label).
Last updated: 2026-03-10
Safety Summary
Most common adverse reactions: nausea with or without vomiting (~10%), injection site inflammation (~10%), and facial/hand flushing (2-5%) (FDA Label, Section 6.1). Nausea is most evident at treatment initiation and tends to decrease with continued use. Other reported reactions: skin rashes, pruritus of ear lobes, nocturia, feverish sensation, pain in eyes, poor appetite, abdominal pain, pedal edema, salty taste (FDA Label, Section 6.1). Post-marketing reports include urticaria, arthralgia, musculoskeletal pain, hypertension, diarrhea, polyuria, dizziness, headache, paresthesia, tremor, visual disturbance (FDA Label, Section 6.2). In the Phase 2 oral formulation trial (NCT01292187), abdominal discomfort (10.5% vs 2.3% placebo) and arthralgia (11.6% vs 2.3% placebo) were more common with active treatment. The FDA label contains a cancer risk warning based on a meta-analysis of 21 RCTs showing malignancy rates of 4.1% (sCT) vs 2.9% (placebo), risk difference 1.0% (95% CI 0.3-1.6%) (FDA Label, Section 6.1). Serious hypersensitivity reactions including fatal anaphylaxis have been reported; skin testing should be considered before treatment (FDA Label, Section 5.1). Hypocalcemia with tetany and seizures has been reported; correct hypocalcemia before initiating therapy (FDA Label, Section 5.2). Circulating antibodies develop in approximately 50% of Paget's disease patients after 2-18 months, sometimes leading to loss of response (FDA Label, Section 6.3). Urine sediment abnormalities (coarse granular casts) were observed in young adult volunteers at bed rest receiving injectable sCT (FDA Label, Section 5.5).
Known Side Effects
common
common
common
common
common
uncommon
uncommon
uncommon
uncommon
uncommon
rare
rare
rare
Who Should NOT Use This
Serious hypersensitivity reactions including fatal anaphylaxis, bronchospasm, and swelling of tongue or throat have been reported. Skin testing should be considered prior to treatment (FDA Label, Sections 4 and 5.1).
Hypocalcemia must be corrected before initiating therapy. Calcitonin further lowers calcium levels. Provisions for parenteral calcium administration should be available during initial administrations (FDA Label, Section 5.2).
No human studies. Animal studies showed decreased fetal birth weights in rabbits at 4-18 times recommended human dose (FDA Label, Section 8.1).
No information on presence in human milk. Calcitonin inhibits lactation in rats. Benefits and risks should be weighed (FDA Label, Section 8.2).
Meta-analysis of 21 RCTs showed increased malignancy risk: 4.1% sCT vs 2.9% placebo, risk difference 1.0% (95% CI 0.3-1.6%). Periodic re-evaluation of continued therapy recommended (FDA Label, Sections 1.4 and 5.3).
Concomitant use may reduce plasma lithium concentrations due to increased urinary clearance. Lithium dose may require adjustment (FDA Label, Section 7).
Talk to Your Doctor
Before considering Calcitonin Salmon (Miacalcin, Fortical), discuss it with your healthcare provider. Ask about potential interactions with your current medications, whether it is appropriate for your health conditions, and what monitoring may be needed.
Sources: [1-15]
Evidence Assessment
Tier 1: FDA-approved prescription drug with multiple approved indications (Paget's disease, hypercalcemia, postmenopausal osteoporosis) supported by Phase 3 RCTs and decades of clinical use (FDA Label; Drugs@FDA active listings for injectable ANDAs and Fortical NDA 021406). The PROOF trial (N=1255, 5 years, PMID 10996576) provided pivotal fracture reduction data for nasal spray (33% reduction at 200 IU). Regulatory approval, not the magnitude of the osteoporosis effect, is what defines the tier; the injectable label states fracture reduction has not been demonstrated for injection product (FDA Label). Two large Phase 3 RCTs (NCT00486434, NCT00704847; N=2206) tested oral formulation for knee OA but did not demonstrate significant efficacy (PMID 25582279). Phase 2 data support oral formulation for osteopenia prevention (NCT01292187, N=129, p=0.0265 for BMD). A Phase 2 PK/PD study (NCT00620854, N=24) confirmed rapid bone-resorption suppression across oral and nasal formulations. Meta-analysis of intranasal therapy (PMID 34879875, 12 studies) confirmed biochemical activity but not BMD superiority. Now considered second-line for osteoporosis due to modest efficacy versus newer agents and cancer risk signal.
1A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group.PMID 10996576
Chesnut CH 3rd, Silverman S, Andriano K, et al. - The American Journal of Medicine (2000) - RCT (Phase 3) - N=1255 randomized
5-year double-blind RCT. 200 IU nasal spray significantly reduced new vertebral fractures by 33% (51/287 vs 70/270, RR=0.67, 95% CI 0.47-0.97, P=0.03). 100 IU and 400 IU groups were not significant. Lumbar spine BMD increased 1-1.5% in all active groups. C-telopeptide suppressed by 12-14%.
Limitations: High dropout rate (only 511 of 1255 completed 5 years). Lack of dose-response relationship (200 IU effective, 400 IU not). Novartis-affiliated investigators.
2Treatment of symptomatic knee osteoarthritis with oral salmon calcitonin: results from two phase 3 trialsNCT00486434 and NCT00704847PMID 25582279
Karsdal MA et al. - Osteoarthritis and Cartilage (2015) - RCT (Phase 3) - N=2206
Oral salmon calcitonin 0.8 mg daily for 2 years showed no significant differences versus placebo in efficacy endpoints or adverse events in patients with knee OA. This was the largest RCT of oral sCT.
Limitations: Oral formulation did not demonstrate efficacy for OA.
3A Study of Oral Recombinant Salmon Calcitonin (rsCT) to Prevent Postmenopausal OsteoporosisNCT01292187
Krause DS (Tarsa Therapeutics) - ClinicalTrials.gov (2014) - RCT (Phase 2) - N=129 (86 active, 43 placebo)
Oral rsCT 200 mcg daily for 54 weeks showed significant LS BMD preservation: +1.03% (95% CI 0.46-1.59) vs -0.12% (95% CI -0.94 to 0.71) placebo (p=0.0265). CTx-1 decreased -11.83% vs +8.37% (p=0.034). Mean age 67 years.
Limitations: Small sample size (N=129). Industry-sponsored (Tarsa Therapeutics). No fracture endpoint. Higher dropout in active group (17/86 vs 13/43). SAEs: 6/86 active vs 2/43 placebo.
4A Dose Selection Study of Oral Recombinant Salmon Calcitonin (rsCT) in Normal, Healthy, Postmenopausal WomenNCT00620854
Tarsa Therapeutics investigators - ClinicalTrials.gov (2008) - RCT (Phase 2, crossover PK/PD) - N=24 healthy postmenopausal women
Single-dose oral rsCT A 150 mcg, oral rsCT B 200 mcg, and Fortical 200 IU intranasal reduced plasma CTx-1 by 74.17% (SE 2.44), 71.99% (SE 2.88), and 68.40% (SE 2.80) respectively. Demonstrates rapid antiresorptive pharmacodynamics across formulations.
Limitations: Short, single-dose biomarker study in healthy volunteers. Does not establish fracture or BMD outcomes. Industry-sponsored (Tarsa Therapeutics). N=22 per-protocol completers.
5A meta-analysis of the therapeutic effect of intranasal salmon calcitonin on osteoporosisPMID 34879875
Li et al. - European Journal of Medical Research (2021) - Meta-analysis - 12 studies, 1068 cases
Intranasal salmon calcitonin lowered blood calcium and improved some biochemical indices, but did not confirm clear advantages for lumbar or hip BMD and did not show that combination therapy was clearly better than conventional treatment alone.
Limitations: Conclusions depend on heterogeneous underlying trials; strongest effects were biochemical rather than hard skeletal endpoints.
6Salmon calcitonin: a review of current and future therapeutic indicationsPMID 18071651
Chesnut CH 3rd, Azria M, Silverman S, et al. - Osteoporosis International (2008) - Review - N/A (review)
Comprehensive review covering calcitonin salmon's mechanism, clinical applications for osteoporosis (including PROOF trial data), Paget's disease, hypercalcemia, and analgesic properties. Discusses fracture pain management and potential future indications including OA.
Limitations: Review article, not original research. Published 2008, pre-dates the 2013 EMA restriction and cancer risk meta-analysis.
7Investigating predictors of pain events during trials of knee osteoarthritis: A post-hoc analysis of two phase III trialsPMID 41647650
Kaaber AB et al. - Osteoarthritis and Cartilage Open (2026) - Post-hoc analysis of Phase 3 RCTs - N=2206
Post-hoc analysis of the oral sCT Phase 3 knee OA trials. Of 8183 AEs over 2 years, 27.6% were pain events. Female sex, insomnia, and depression were predictors of pain events.
Limitations: Post-hoc analysis is hypothesis-generating. Multiple testing without adjustment.
8Weight loss ameliorates symptoms of osteoarthritis and is correlated with alterations in soluble bone and cartilage markersPMID 41764561
Bay-Jensen AC et al. - BMC Rheumatology (2026) - Post-hoc analysis of Phase 3 RCTs - N=806
Post-hoc analysis of 806 knee OA patients from oral sCT trials. Weight loss >=5% associated with improved WOMAC scores and reduced synovial inflammation (C3M decreased 0.84-fold). However, CTX-I increased 1.58-fold in weight loss group.
Limitations: Post-hoc analysis. Biomarker findings from a trial where sCT did not show primary endpoint efficacy. Authors are employees/shareholders of Nordic Bioscience.
9Preliminary evaluation of the clinical efficacy of salmon calcitonin nasal spray in patients with rotator cuff tears after arthroscopic repairPMID 41570289
Lyu F et al. - International Journal of Surgery (2026) - Retrospective cohort - N=270 (150 study, 120 control)
SCNS improved early postoperative VAS, CMS, and SST scores at 3 months (p<0.05). Re-tear rate significantly lower in SCNS group: 1.3% (2/150) vs 10.0% (12/120), p<0.05. Functional advantages did not persist at 6 and 24 months.
Limitations: Retrospective design. No randomization. Early functional benefits did not persist.
10Sex-specific responses on alcohol intake in rodents following sCT infusion in the middle part of the paraventricular nucleus of the thalamusPMID 41763298
Aranas C et al. - Neuropharmacology (2026) - Animal study (rodents) - Multiple rodent experiments
CTR detected in mid-PVT. Locally infused sCT decreased alcohol intake in male Wistar rats (p=0.0048) but not females. sCT attenuated alcohol-induced locomotor stimulation and dopamine release in NAc in male mice.
Limitations: Animal study only. Sex-specific effects. No human translation data.
11The calcitonin receptor controls osteophyte formation, but not cartilage degeneration and subchondral bone loss in experimental osteoarthritisPMID 41717838
Jiang S et al. - Bone & Joint Research (2026) - Animal study (mouse model) - CTR-deficient and WT mice
CTR was progressively induced in post-traumatic OA joints. CTR-deficient mice showed decreased osteophyte formation but no difference in cartilage deterioration.
Limitations: Animal study. ACLT-induced model. Global CTR knockout.
12Development of a Long-Acting and Stapled Dual Amylin and Calcitonin Receptor Agonist as Monotherapy and Combination with GLP-1R Agonists for the Treatment of ObesityPMID 41429154
Zhou Y et al. - Bioconjugate Chemistry (2026) - Preclinical (in vitro + animal) - Diet-induced obese rats
UDA-6, a long-acting stapled DACRA based on salmon calcitonin template, showed potent activation of AMY3R and CTR. Combination with semaglutide or tirzepatide yielded up to 41% vehicle-adjusted body weight reduction.
Limitations: Preclinical only. Modified sCT derivative, not native sCT.
13Nanostructural changes in bone quality in a mouse model of chronic kidney disease and treatment with calcitoninPMID 41211539
Montagnino E et al. - Bone Reports (2025) - Animal study (mouse model) - CKD mouse model
sCT at 50 IU/kg/day 5x/week for 5 weeks in CKD mice increased collagen weight percent but did not affect cortical porosity, thickness, bone geometry, or nanostructural mineral parameters.
Limitations: Animal study. Short treatment duration. Single dose.
14Clinical Characteristics and Prognosis of Patients with Non-Hodgkin Lymphoma Complicated by HypercalcemiaPMID 40936125
Lin Y et al. - Zhongguo Shi Yan Xue Ye Xue Za Zhi (2025) - Retrospective clinical study - N=47 NHL patients with hypercalcemia
44.7% (21/47) received salmon calcitonin treatment. 80.8% (38/47) had calcium return to normal with median recovery time of 6 days.
Limitations: Retrospective. Small sample. Chinese language.
15Does salmon calcitonin cause cancer? A review and meta-analysis
Wells G, Chernoff J, Gilligan JP, Krause DS - Osteoporosis International (2016) - Review and meta-analysis - Meta-analysis of clinical trials
Questioned whether the cancer risk signal from calcitonin salmon trials represents a true causal relationship.
Limitations: Authors include Tarsa Therapeutics CMO (Krause DS), potential conflict of interest.