Chicken calcitonin: bone and calcium research peptide
A lab version of a peptide hormone that regulates calcium and bone density; used by researchers to study how calcitonin-type signals work in the body; research tool, not an approved drug.
A researcher, an agent, or an algorithm wrote down the sequence and picked a target to hit.
An AI model like OpenFold3 or AlphaFold built a 3D structure and scored how well it fits the binding site.
A second contributor repeated the computation on their own hardware and the scores matched.
Named peptide fragment — synthesized for research; ClinicalTrials.gov trials registered for parent compound or class
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Endogenous peptide fragment — receptor binding/activity established in published literature; CT.gov evidence
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What this is
Salmon calcitonin is a synthetic form of a 32-amino acid peptide hormone that fish produce naturally in the ultimobranchial body. It is used therapeutically because it is approximately 40–50 times more potent than the equivalent human hormone at the human calcitonin receptor — a difference attributed to its amphipathic alpha-helical structure and greater resistance to enzymatic degradation. The human endogenous calcitonin is produced by parafollicular C-cells of the thyroid gland and acts as a counter-regulator to parathyroid hormone in calcium homeostasis. The stored sequence (CASLSTCVLGKLSQELHKLQTYPRTDVGAGTP) represents the linear backbone; the active peptide forms a disulfide bond between Cys1 and Cys7 that is essential for biological activity but is not visible in the raw 32-letter string.
Salmon calcitonin has been available as an FDA-approved prescription drug since 1975 under brand names including Calcimar, Miacalcin, and Fortical. Also known as: sCT, Miacalcin, Fortical, calcitonin-salmon.
History
Calcitonin was first characterized as a calcium-lowering peptide hormone in the 1960s, produced by the thyroid's parafollicular C-cells. The therapeutic insight that salmon calcitonin — produced naturally by ultimobranchial body cells in fish — was far more potent than human calcitonin at the human calcitonin receptor led directly to the development of synthetic salmon calcitonin as a drug. Salmon calcitonin received FDA approval in 1975 for Paget's disease of bone, hypercalcemia of malignancy, and postmenopausal osteoporosis. The intranasal spray formulation (Miacalcin Nasal Spray) was approved in 1995, improving patient acceptability for chronic use.
The PROOF trial (Prevent Recurrence of Osteoporotic Fractures) subsequently demonstrated vertebral fracture reduction at the 200 IU/day intranasal dose in postmenopausal women with osteoporosis, though fracture reduction was not demonstrated at the 100 IU/day or 400 IU/day doses — an anomalous dose-response that limited guideline endorsement. In 2012, the EMA's Committee for Medicinal Products for Human Use conducted a meta-analysis of 21 trials that identified a small but consistent increase in malignancy risk (approximately 0.7–2.4 percentage points absolute excess) in long-term users. The FDA issued labeling changes in 2013 and the EMA restricted the intranasal form from the postmenopausal osteoporosis indication in the EU entirely. Use has declined substantially since 2013 in favor of bisphosphonates, denosumab, and the anabolic agents, though calcitonin retains specific niches: acute hypercalcemia management, Paget's disease, and adjunctive analgesia for acute vertebral compression fractures.
What it does
Salmon calcitonin reduces bone breakdown and lowers blood calcium. It acts directly on the cells that resorb bone (osteoclasts), causing them to retract from bone surfaces. This mechanism supports its use in conditions involving excessive bone resorption or dangerously elevated calcium levels.
In Paget's disease of bone and hypercalcemia of malignancy, the bone-resorption inhibition is the primary therapeutic effect. In postmenopausal osteoporosis, the effect on bone mineral density is modest compared with bisphosphonates or anabolic agents, and the drug is now used only when alternatives are not suitable.
Salmon calcitonin may also have analgesic effects in acute vertebral compression fractures. This analgesic action is thought to be mediated through central pathways — involving serotonergic signaling and beta-endorphin release — rather than through peripheral bone mechanisms, though the mechanism is described in the literature as proposed and not fully characterized (Hay and colleagues, British Journal of Pharmacology 2018).
Evidence
- Human: FDA-approved for Paget's disease of bone, hypercalcemia of malignancy, and postmenopausal osteoporosis (label data); vertebral fracture reduction demonstrated in the PROOF trial at the 200 IU/day intranasal dose over 5 years; analgesic benefit in acute vertebral compression fracture supported by some trials but meta-analyses are heterogeneous in conclusion.
- Animal: Comprehensive characterization across species; calcitonin receptor biology thoroughly described in the literature (Granholm and colleagues, Journal of Cellular Biochemistry 2008).
- In vitro: Calcitonin receptor binding, osteoclast retraction, and cAMP/calcium signaling have been characterized at the molecular level (Lee and colleagues, Journal of Biological Chemistry 2016; Barwell and colleagues, British Journal of Pharmacology 2012).
Known effects
- Inhibition of osteoclast-mediated bone resorption — FDA-approved (Paget's disease of bone, postmenopausal osteoporosis, hypercalcemia of malignancy)
- Serum calcium reduction in hypercalcemia of malignancy — FDA-approved; onset within hours; tachyphylaxis limits extended use
- Vertebral fracture reduction in postmenopausal osteoporosis — Phase III RCT (PROOF trial); effect demonstrated at 200 IU/day intranasal only
- Adjunctive analgesia in acute vertebral compression fracture — Partially supported; trials with mixed results; meta-analyses heterogeneous
Safety signals
A small but consistent increase in malignancy risk with long-term use was identified in the 2012 EMA meta-analysis of 21 trials, with an absolute risk increase of approximately 0.7–2.4 percentage points in long-term users. The causal biological mechanism is incompletely characterized. This signal was sufficient to prompt the 2013 FDA labeling update (restricting osteoporosis use to patients for whom alternatives are not suitable) and EMA removal of the intranasal postmenopausal osteoporosis indication in the EU.
Additional signals from label and clinical trial data: nasal irritation, dryness, and minor epistaxis (intranasal form; reduced by alternating nostrils); nausea (both formulations); flushing (parenteral administration); injection-site reactions (parenteral form); neutralizing antibody formation in a meaningful proportion of long-term users (clinical significance and predictors of response loss not fully characterized); hypocalcemia risk in patients with pre-existing hypocalcemia (contraindication); reduced serum lithium concentration (pharmacodynamic interaction — lithium monitoring described in available literature as potentially necessary); anaphylaxis and serious hypersensitivity reactions, including in patients without prior exposure (contraindication for known hypersensitivity).
Regulatory status
- US (FDA): Approved prescription drug. Salmon calcitonin (Miacalcin, Fortical, generics) is approved for postmenopausal osteoporosis (intranasal, 200 IU/day), Paget's disease of bone, and hypercalcemia of malignancy. 2013 labeling update advises osteoporosis use only when alternatives are not suitable. Not a controlled substance.
- EU (EMA): Approved with significant restrictions since 2012. Intranasal salmon calcitonin is no longer approved for postmenopausal osteoporosis in the EU; restricted to short-term use (up to 4 weeks) for prevention of acute bone loss due to sudden immobilization, Paget's disease in patients unresponsive to alternatives, and hypercalcemia of malignancy. US labeling is less restrictive than the EU position.
- UK (MHRA): Aligned with EMA restrictions per available literature; current status should be independently verified against current MHRA documentation.
- WADA: Not specifically listed on the WADA Prohibited List per available literature; no established performance-enhancing pharmacology in athletes with normal bone metabolism. Current list status not independently refreshed in this card.
Mechanism
Salmon calcitonin acts as an agonist at the calcitonin receptor (CTR), a Class B (secretin family) G-protein-coupled receptor expressed on osteoclasts. CTR is one of 15 human family B GPCRs and, along with the calcitonin receptor-like receptor (CLR), is a pharmacologically important receptor whose biology is shaped by heterodimerization with receptor activity-modifying proteins (RAMPs) — RAMP1, RAMP2, and RAMP3 — forming amylin receptor complexes (AMY1–3), the CGRP receptor, and adrenomedullin receptors (Barwell and colleagues, British Journal of Pharmacology 2012; Hay and colleagues, British Journal of Pharmacology 2018).
On osteoclasts, CTR activation by calcitonin triggers intracellular cAMP and calcium signaling cascades, causing rapid osteoclast retraction from bone surfaces and inhibiting bone resorption. Expression of CTR on bone marrow macrophage-derived osteoclast precursors is upregulated by RANKL during osteoclast differentiation (Granholm and colleagues, Journal of Cellular Biochemistry 2008). The mechanistic interactions between calcitonin and amylin receptor complexes — relevant to understanding cross-reactivity with amylin analogs — have been further characterized using peptide interaction studies (Lee and colleagues, Journal of Biological Chemistry 2016). The RAMP-dependency of CTR pharmacology has been reviewed in the context of broader Class B GPCR allosteric modulation (Advances in Pharmacology 2020).
Analgesic effects in acute vertebral compression fractures are proposed to be mediated centrally via serotonergic signaling and beta-endorphin release rather than peripherally, though this mechanism is not fully characterized.
Salmon calcitonin's enhanced potency relative to human calcitonin is attributed to its amphipathic alpha-helical structure, which confers greater receptor affinity and resistance to enzymatic degradation.
Open questions
- Mechanism of malignancy signal: The biological mechanism underlying the small but consistent cancer risk increase identified in the 2012 EMA meta-analysis is incompletely characterized. Patient-level predictors of malignancy risk with long-term use are not defined.
- Analgesic effect in acute vertebral compression fracture: Trial data are mixed and meta-analyses heterogeneous. The precise magnitude of benefit and patient subgroups most likely to respond are unresolved.
- Neutralizing antibody formation and clinical impact: A meaningful proportion of long-term users develop neutralizing antibodies. Clinical significance, predictors of response loss, and whether antibody titers should guide therapeutic decisions are not fully characterized.
- Calcitonin family receptor crosstalk: The calcitonin family of peptides (CGRP, amylin, adrenomedullin) shares receptor systems mediated by CTR and CLR in combination with RAMPs. Mechanistic crosstalk and off-target effects via related receptor complexes are incompletely parsed and may be relevant to interpreting calcitonin's full pharmacological profile (Hay and colleagues, British Journal of Pharmacology 2018).
Related peptides
The calcitonin receptor family includes several therapeutically relevant peptides sharing CTR or CLR/RAMP receptor systems. Amylin analogs such as cagrilintide act at CTR/RAMP complexes (AMY1–3), overlapping pharmacologically with calcitonin's receptor targets. CGRP-related peptides act at the CLR/RAMP1 complex (the CGRP receptor), which is the molecular basis for CGRP-targeting migraine therapies. Teriparatide, a parathyroid hormone analog, acts on the opposing axis of calcium homeostasis — stimulating bone formation rather than inhibiting resorption — and is now preferred over calcitonin for severe osteoporosis with high fracture risk.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.8508142232894897 | openfold3-mlx |
| ranking score | 0.9531683921813965 | openfold3-mlx |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.788 | global PDE — lower = better |
| disorder | 0.255 | fraction disordered |
| chain pair ipTM (A, B) | 0.851 | interface quality |
▸3-letter notation
▸recipeopenfold3-mlx 0.3.1
| parameter | value |
|---|---|
| model | openfold3-mlx 0.3.1 |
| weights | aedd8f3eb814e392… |
| hardware | apple_m4_base_16gb |
| mlx version | 0.31.1 |
| python | 3.14.3 |
| random seed | 42 |
| msa strategy | colabfold |
| diffusion samples | 1 |
| runtime | 452s |
| predicted by | mlx@peptide |
| predicted at | 2026-04-25 |
python3 openfold3/run_openfold.py predict --query_json {query.json} --runner_yaml examples/example_runner_yamls/mlx_runner.yml --output_dir {output_dir} --num_diffusion_samples 1 ▸citationbibtex
@peptide{pep10509,
sequence = {CASLSTCVLGKLSQELHKLQTYPRTDVGAGTP},
target = {calcr},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}