Evidence Grade A — Regulatory approved. 44 published studies. 139 registered clinical trials.
Medically reviewed by a licensed medical professional
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Calcitonin-salmon (sold as Miacalcin and generics) is a synthetic version of a bone-regulating hormone, available mainly as a nasal spray. It slows the breakdown of bone and has been used for osteoporosis, Paget's disease of bone, and to quickly bring down dangerously high blood calcium levels. It also has a notable pain-relieving effect on bone pain, particularly from spinal fractures.
Calcitonin-salmon is also known by these brand and alternate names:
44 published studies: 28 human, 6 animal, 1 in-vitro, 10 reviews
Calcitonin-salmon is marketed as Miacalcin and generic equivalents (injection approved 1986, nasal spray approved 1995). It is used for postmenopausal osteoporosis, Paget's disease of bone, and emergency treatment of high blood calcium.
The PROOF trial showed a 33% reduction in vertebral fractures with the nasal spray, though this finding has been debated due to high dropout rates. In 2013, the European Medicines Agency recommended withdrawing calcitonin nasal spray due to a small increased risk of cancer with long-term use, though the FDA kept it available with duration-of-use guidance. Calcitonin has largely been superseded by more effective osteoporosis treatments like bisphosphonates, denosumab, and bone-building agents, but retains a role in acute pain management for vertebral compression fractures and emergency calcium-lowering.
Calcitonin works by directly targeting osteoclasts — the cells responsible for breaking down bone. When calcitonin binds to receptors on these cells, it causes them to shrink, detach from bone surfaces, and stop resorbing bone. This slows bone loss. Calcitonin also has a pain-relieving effect on bone pain that appears to work through the central nervous system, which is why it has been used for painful vertebral fractures. The salmon form is used because it is 40–50 times more potent than human calcitonin.
The PROOF trial reported a 33% reduction in spinal fractures with the nasal spray, though that finding has been questioned due to high dropout rates during the study. A more significant concern emerged in 2013 when European regulators identified a small increased risk of cancer with long-term use, leading them to recommend withdrawal of the nasal spray. US regulators kept it available but added guidance to limit treatment duration. In practice, calcitonin has been largely replaced by more effective osteoporosis treatments — bisphosphonates, denosumab, and bone-building agents like teriparatide all offer stronger fracture protection. Calcitonin still has a recognised role in managing the acute pain of spinal compression fractures and in emergency calcium-lowering, but it is no longer a front-line osteoporosis treatment. Ongoing research is limited.
PeptideTrace tracks 139 registered clinical trials for Calcitonin-salmon sourced from ClinicalTrials.gov.
Procalcitonin Guided Versus Conventional Antibiotic Therapy in Patients With Sepsis in the ICU
STAGE-MTC Trial Thyroid Lobectomy With Ipsilateral Central Neck Dissection
Using Virtual Reality to Teach Mindfulness to People With Migraine
Chinese Real-world Study of Treatment of Vestibular Migraine
A Study to Compare Blood Levels of Different Dosage Formulations of the Study Medicine That Is a CGRP Receptor Antagonist in Healthy Adults
Health Canada Market Authorisation
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Calcitonin-salmon is a synthetic 32-amino-acid peptide identical to salmon calcitonin, which is 40–50 times more potent than human calcitonin at the calcitonin receptor. It is available as a nasal spray (primary formulation in current use) and was formerly available as injectable solution.
Calcitonin binds the calcitonin receptor (CTR, a class B GPCR) on osteoclasts, activating cAMP and causing osteoclast contraction, detachment from bone surfaces, and inhibition of bone resorption. It also produces a centrally mediated analgesic effect on bone pain (mechanism not fully understood but may involve endorphin modulation). The antiresorptive effect is subject to receptor downregulation (tachyphylaxis) with prolonged use, limiting long-term efficacy.
Calcitonin-salmon nasal spray is marketed as Miacalcin and generic equivalents (injection approved 1986, nasal spray approved 1995). Indications include postmenopausal osteoporosis (nasal 200 IU daily), Paget's disease, and hypercalcemia of malignancy (injection). The PROOF trial (N=1,255; 5 years) showed the 200 IU nasal dose reduced vertebral fractures by 33% (RR 0.67; P=0.03), but there was no clear dose-response and no nonvertebral fracture benefit. The trial had a 59% dropout rate. In 2013, an FDA advisory committee voted 12-9 that the cancer signal (OR 1.61; 4.1% vs 2.9% placebo) outweighed the modest benefits. The FDA kept it on the market with restricted labeling. The EMA suspended the nasal spray.
Linaclotide is marketed as Linzess (approved August 2012). It is taken as a daily oral capsule on an empty stomach, at least 30 minutes before the first meal. The recommended dose is 290 mcg for IBS-C and 72 or 145 mcg for chronic constipation. In clinical trials, approximately 34% of IBS-C patients met the composite improvement endpoint compared to 17% on placebo. Diarrhoea is the most common side effect (approximately 20%) and the leading reason for discontinuation. Linaclotide has a boxed warning against use in children under 6 years due to deaths in young mice, though no such events have been reported in humans. It competes with plecanatide (which targets the same pathway) and other IBS-C treatments.
Elamipretide (Forzinity) was approved by the FDA for Barth syndrome based on the TAZPOWER trial. The randomised crossover phase (12 patients) did not meet its primary endpoints, but the open-label extension (168 weeks) demonstrated durable improvements in walking distance and muscle strength that formed the basis for approval. Barth syndrome affects approximately 1 in 300,000–400,000 births. A larger Phase III trial in primary mitochondrial myopathy (218 patients, MMPOWER-3) did not meet its primary endpoint, and the drug was not approved for that broader indication. Elamipretide remains approved exclusively for Barth syndrome. See also SS-31 (#158) for the research compound context.
Glucagon has been available as an emergency injection since the 1960s and remains the standard rescue treatment for severe hypoglycaemia. Recent innovation has focused on making it easier to administer in emergencies. Baqsimi, approved in 2019, was the first needle-free option as a nasal powder. Gvoke, also approved in 2019, eliminated the need to mix and reconstitute the medication before injection — a significant advance since severe hypoglycaemia often impairs the ability to follow complex preparation steps. Dasiglucagon (Zegalogue), a next-generation stable liquid glucagon approved in 2021, further improved on the convenience of rescue administration. Beyond emergency rescue, glucagon's receptor is now a major research target — dual and triple agonists combining glucagon receptor activity with GLP-1 (such as survodutide and retatrutide) are in advanced clinical trials for obesity and metabolic disease.
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