Calcitonin salmon (Miacalcin)

Summary

Calcitonin is a 32 amino acid hormone that lowers blood calcium by slowing osteoclasts, the cells that break down bone; the drug form is synthetic salmon calcitonin, FDA approved as an injection since 1975 for Paget disease (a disorder of abnormal, weakened bone growth) and hypercalcemia (high blood calcium) and as a nasal spray since 1995 for postmenopausal osteoporosis. Its osteoporosis evidence is weak: the 5 year PROOF trial found a 33% reduction in new vertebral (spine) fractures only at the 200 IU dose, with no dose response (the effect did not rise with dose) and 59% dropout. In 2013 an FDA meta-analysis (a pooled analysis) of 21 trials found malignancy (cancer) in 4.1% of calcitonin treated patients versus 2.9% on placebo, and FDA restricted the osteoporosis indication to women more than 5 years past menopause for whom alternatives are not suitable.

What is Calcitonin?

Calcitonin is a 32 amino acid thyroid C cell hormone; the drug is synthetic salmon calcitonin, which is more potent and longer acting than the human form. It is also known as Calcitonin-salmon, Salmon calcitonin, Miacalcin, Fortical, Calcimar, sCT.

How does it work?

Calcitonin binds the calcitonin receptor on osteoclasts and rapidly inhibits bone resorption, lowering serum calcium; it also increases renal calcium excretion. The effect on osteoclasts wanes with continuous exposure (escape phenomenon), which limits its potency compared with bisphosphonates. Salmon calcitonin is about 40 to 50 times more potent than human calcitonin at the receptor. Calcitonin also has a central analgesic effect that is exploited for painful vertebral fractures.

FDA-approved uses of Calcitonin

Yes. The Miacalcin injection label covers symptomatic Paget disease of bone (a disorder that makes bone grow abnormally and weaken) when alternative treatments are not suitable, hypercalcemia (high blood calcium), and postmenopausal osteoporosis when alternative treatments are not suitable. The nasal spray is labeled only for postmenopausal osteoporosis in women more than 5 years past menopause when alternatives are not suitable. Both labels state that fracture reduction has not been demonstrated and that the need for continued therapy should be reassessed periodically because of a possible association with malignancy (cancer). [4] [6]

What does the evidence say about Calcitonin?

PROOF (n = 1,255) is the pivotal osteoporosis trial: 5 years of nasal calcitonin 100, 200, or 400 IU daily versus placebo. Only the 200 IU dose reduced new vertebral fractures (relative risk 0.67, 33% reduction); the 100 and 400 IU doses did not, there was no dose response, bone density gains were about 1 to 1.5%, and 59% of participants dropped out, all of which weaken the result. Hip and nonvertebral fractures were not reduced. Efficacy in Paget disease and hypercalcemia is documented in older controlled studies summarized in the label. A 2016 meta-analysis reviewed the malignancy signal that FDA had identified in 2013 and found the association weak and inconsistent across studies.

Human evidence

Chesnut 2000 (PROOF): 1,255 postmenopausal women with established osteoporosis randomized to nasal salmon calcitonin 100, 200, or 400 IU daily or placebo for 5 years; new vertebral fractures 200 IU versus placebo relative risk 0.67 (95% CI 0.47 to 0.97); no significant reduction at 100 or 400 IU; lumbar spine BMD rose 1 to 1.5%; 59% withdrew. FDA 2013: meta-analysis of 21 randomized trials found malignancies in 4.1% of calcitonin treated versus 2.9% of placebo treated patients, driven heavily by one 5 year trial; FDA concluded causality could not be established but restricted the osteoporosis indication. Wells 2016: independent meta-analysis found the cancer association was not consistent across trials.

Animal evidence

Salmon calcitonin was characterized in rat and rabbit models of hypercalcemia and bone resorption in the 1960s and 1970s. Animal carcinogenicity studies did not predict the malignancy signal later seen in human trial meta-analyses, and no mechanism for it has been established.

Key studies

Conditions studied

Is Calcitonin legal in the United States?

FDA and compounding status

FDA approved as Calcimar and later Miacalcin injection in 1975 for Paget disease and hypercalcemia, with postmenopausal osteoporosis added, and as Miacalcin nasal spray in 1995 for osteoporosis; Fortical nasal spray (2005) and generic calcitonin-salmon nasal sprays followed. In March 2013 an FDA advisory committee reviewed the malignancy meta-analysis and the labels were revised to restrict osteoporosis use to women more than 5 years postmenopause for whom alternatives are not suitable and to require periodic reassessment. The European Medicines Agency withdrew nasal calcitonin for osteoporosis in 2012. Compounding is limited to patient specific needs because approved products exist.

WADA status

Not WADA prohibited. Not named on the current prohibited list. Athletes should still confirm against the list in force for their season.

Regulatory timeline

No regulatory events recorded.

Full tracker for Calcitonin or the category-wide tracker.

Calcitonin dose on the FDA label

Doses below are quoted from the FDA label for its approved uses, plus the doses used in the pivotal trials where noted. The prescriber sets the dose; PeptideAgent does not recommend doses or protocols.

FDA labels (DailyMed). Miacalcin injection, by subcutaneous or intramuscular injection: symptomatic Paget disease of bone, 100 USP units daily; hypercalcemia, 4 USP units/kg every 12 hours, increased to 8 units/kg every 12 hours if the response is unsatisfactory after 1 to 2 days, and to a maximum of 8 units/kg every 6 hours after 2 more days; postmenopausal osteoporosis in women more than 5 years past menopause, 100 USP units daily. Calcitonin salmon nasal spray, postmenopausal osteoporosis: one spray (200 USP units) daily, alternating nostrils, with at least 1,000 mg of elemental calcium and 400 IU of vitamin D a day.

Routes reported

What are the side effects and interactions of Calcitonin?

Side effects

Interactions

Contraindications

How do people access Calcitonin legally?

Typical cost: Generic calcitonin-salmon nasal spray costs roughly 50 to 200 USD per month at cash prices; brand Miacalcin nasal spray lists higher. Injection vials cost roughly 100 to 300 USD each. Insurance coverage for osteoporosis is limited given the restricted indication.

• Rules by state
• Verified provider directory

Frequently asked questions

Decisions about starting, stopping, or combining any treatment belong with a licensed clinician who knows your history.

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Sources

Numbered citations above point to these primary sources. PubMed entries link to the indexed abstract.