Section 01
What it's used for
Approved for osteoporosis
This is FDA-approved for osteoporosis after menopause. In studies, it lowered the risk of spinal (vertebral) bone fractures by 33%. The most common way to take it is a nasal spray, at 200 IU per day, though other forms exist.
▸Clinical wording
FDA-approved for postmenopausal osteoporosis. Reduces vertebral fracture risk by 33%. Nasal spray (200 IU/day) is the most common route.
Approved for Paget's disease
This is an approved use for Paget's disease, a condition where bone is broken down and rebuilt too fast, causing weak or deformed bone. Researchers observed that it slows this bone turnover process and eases the pain it causes.
▸Clinical wording
Reduces bone turnover and pain.
Pain relief after a spinal fracture
Researchers observed pain-relieving (analgesic) benefits within days for people with a recent (acute) break in a spinal bone. This makes it a useful option for managing pain right after this kind of fracture in clinical care.
▸Clinical wording
Provides analgesic benefit within days, useful for acute fracture pain management.
Approved for high calcium from cancer
This is an approved treatment for a sudden, dangerous rise in blood calcium levels (hypercalcemia) caused by cancer. It is used for short-term, urgent (acute) treatment of this condition, rather than for long-term daily use.
▸Clinical wording
Acute treatment of hypercalcemia of malignancy.
Section 02
Mechanism of Action
How the hormone grips its receptor
- Freeze-imaging showed the hormone sitting in a deep pocket that opens as the receptor shifts.
- Parts of the receptor swing outward, letting the signalling partner protein dock inside.
- The response is not uniform, because the receptor gene yields several different versions.
- With helper proteins present, the same receptor behaves instead like an amylin receptor.
▸Clinical wording
Calcitonin receptor engagement and Gs coupling
Cryo-electron microscopy of the full-length human calcitonin receptor bound to peptide agonist and heterotrimeric Gαsβγ shows the ligand occupying an extended hydrophobic pocket opened by outward movement of the extracellular ends of transmembrane helices 6 and 7, a roughly 60-degree kink in helix 6, and an outward swing of its intracellular end that admits the Gαs α5 helix, with an extended helix 8 contacting Gβ. The response is not uniform: CALCR alternative splicing yields isoforms, and co-expression with RAMP1 or RAMP3 in COS-7 cells converts the receptor into amylin-receptor phenotypes with distinct binding and cAMP profiles.
Bone-dissolving cells stop and pull back
- Isolated bone-dissolving cells stopped rippling within minutes of exposure and then retracted.
- The quiescence was complete above a low concentration and reversed when the hormone was washed off.
- Related scavenger cells were unaffected, so the response is specific to this cell type.
- The hormone breaks up the cell's internal scaffolding ring and strips anchoring proteins from it.
▸Clinical wording
Osteoclast quiescence, retraction and cytoskeletal disassembly
Isolated osteoclasts stopped lamellipodial ruffling within minutes of calcitonin exposure and then retracted; quiescence was complete above 50 pg/mL, reversible on washout and abolished by prior trypsin treatment, while macrophages were unaffected. In rat osteoclasts the loss of motility was mimicked by dibutyryl-cAMP and cholera toxin and the retraction by pertussis toxin, ionomycin and raised ambient calcium, and calcitonin produced a biphasic rise in cytosolic calcium. Calcitonin also disrupts the peripheral F-actin ring and strips paxillin, Pyk2 and FAK from it, with Pyk2 dephosphorylated at Tyr402; reviews add loss of the ruffled border while osteoclast number stays unchanged.
Why the effect fades with continued exposure
- In human bone-dissolving cells the hormone cut its own receptor's messenger within twelve hours.
- Signalling activity fell in parallel, and removing the hormone restored the receptor message.
- In mouse cells the hormone induced a repressor protein that drives this shutdown.
- Cells lacking that repressor kept their receptors and were inhibited more strongly than normal cells.
▸Clinical wording
Receptor downregulation underlying the escape phenomenon
In human osteoclast-like multinucleated cells and osteoclastoma giant cells, calcitonin reduced calcitonin receptor mRNA within 12 hours without affecting actin mRNA, and calcitonin-stimulated adenylate cyclase activity fell in parallel; removing the hormone restored the receptor message. In RANKL-differentiated RAW264.7 cells and in primary mouse marrow osteoclasts, calcitonin induced the inducible cAMP early repressor ICER, and in Crem-knockout osteoclasts it no longer downregulated receptor mRNA while inhibiting osteoclast activity more strongly than in wild-type cells.
Switching on vitamin D in the kidney
- In rats with normal blood calcium, one injection sharply raised the kidney's vitamin-D-activating enzyme.
- Conversion of stored vitamin D into its active form increased in the living animals.
- The vitamin D receptor's messenger fell in the kidney as the dose rose.
- Parathyroid hormone raised the enzyme only in vitamin-D-deficient animals with low blood calcium.
▸Clinical wording
Renal induction of 25-hydroxyvitamin D 1-alpha-hydroxylase
In normocalcemic sham-operated and thyroparathyroidectomised rats, a single calcitonin injection markedly raised renal CYP27B1 messenger RNA and increased in vivo conversion of 25-hydroxyvitamin D3 to 1α,25-dihydroxyvitamin D3, while dose-dependently lowering renal vitamin D receptor mRNA. Parathyroid hormone induced CYP27B1 only in vitamin-D-deficient hypocalcemic animals. The authors concluded that under normocalcemic conditions calcitonin rather than PTH is the main driver of renal 1α-hydroxylase expression in this species.
Pain relief with no agreed explanation
- A 2019 review collected mostly rodent evidence spread across several unrelated pain mechanisms.
- Reported effects included changed serotonin handling, fewer sodium channel transcripts and blunted cold-sensor signalling.
- Human mechanistic data amount to raised blood beta-endorphin in migraine and osteoporosis groups.
- No single pathway has been shown to carry the pain-relieving effect.
▸Clinical wording
Central antinociceptive signalling remains poorly resolved
A 2019 review of mechanism studies collects mostly rodent evidence: calcitonin lowered serotonin transporter levels and raised thalamic serotonin receptor expression in osteoporotic rats, reduced sodium channel transcription in dorsal root ganglion neurones in a radicular pain model, blunted TRPM8 and TRPA1 signalling in chemotherapy-induced neuropathy models, and suppressed prostaglandin and thromboxane release. Human mechanistic data are limited to raised plasma β-endorphin in migraine and postmenopausal osteoporosis cohorts. No single pathway has been shown to carry the analgesic effect.
Section 03
Biological Pathways
- CTR-Gs-cAMP Receptor CouplingCryo-EM of CTR with peptide agonist and Gαs shows a roughly 60-degree kink in helix 6 opening the pocket for the Gα5 helix; RAMP1/RAMP3 coexpression converts CTR to an amylin-receptor with distinct cAMP profile.
- Osteoclast Quiescence and RetractionCalcitonin halts osteoclast ruffling within minutes and triggers retraction, complete above 50 pg/mL and reversible on washout; it strips paxillin, Pyk2 and FAK from the F-actin ring.
- Receptor Downregulation (Escape Phenomenon)Calcitonin cuts receptor mRNA within 12 hours in human osteoclast-like cells; in mouse osteoclasts the same downregulation requires the cAMP-induced repressor ICER, lost in Crem-knockout cells.
- Renal Vitamin D Hydroxylase InductionIn normocalcemic rats calcitonin raised renal CYP27B1 mRNA and 1α,25-dihydroxyvitamin D3 production while lowering vitamin D receptor mRNA, making calcitonin the main driver of renal hydroxylase expression.
- Central Analgesia, Mechanism UnresolvedRodent studies link calcitonin to altered serotonin signalling, reduced dorsal root ganglion sodium channel transcription, and blunted TRPM8/TRPA1 signalling; no single analgesic pathway is confirmed in humans.
Section 04
Dosage Information
CSNLSTCVLGKLSQELHKLQTYPRTNTGSGTP-NH2 (salmon calcitonin, 32 aa)| Route / system | Context | Range studied | Limitation |
|---|---|---|---|
| Injection — Paget's disease | FDA label; under the skin or into muscle | 100 units (0.5 mL) a day — about 1.1–1.4 IU/kg for a 70–90 kg adult; the same 100 IU a day covers osteoporosis after menopause. | Europe kept it only as a second choice, capped at three months and six in rare cases; bisphosphonates took over, so this is a fallback, not a standard. |
| Injection — high blood calcium | FDA label, cancer; under the skin or into muscle | 4 IU/kg every 12 hours to start, then 8 IU/kg every 12 hours, at most 8 IU/kg every 6 hours — 280–720 IU per shot at 70–90 kg. | Hospital rescue dosing, set by a measured blood calcium and given with fluids. Two step-ups are built in because the first dose often does too little. |
| Nasal spray | FDA label and a five-year trial in osteoporosis | 200 IU a day, one spray, alternating nostrils — about 2.2–2.9 IU/kg at 70–90 kg. The trial gave 100, 200 or 400 IU to 1,255 women. | Only 200 IU cut spine fractures in five years, not 100 or 400. The EMA pulled the spray in 2012: cancer ran 0.7–2.4 points over placebo, worst this way. |
| Injection — sudden immobility | EU label; under the skin or into muscle | 100 IU a day, or 50 IU twice a day, down to 50 IU a day once movement resumes. Two weeks is the course, four weeks the hard maximum. | The four-week cap is regulatory, not biological: cancer risk tracks how long it is taken. Repeat courses were never approved and the US label lacks this use. |
Results
Syringe Fill Level (100u syringe)
Set positive values for: Recommended dose per kg.
Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.
Section 05
Protocols
No protocols featuring this peptide yet. Browse All Protocols
Section 06
Stability & Storage
Storing the product
The nasal spray is kept at room temperature, up to 25°C, before opening. Injectable calcitonin is kept at 2-8°C. Salmon calcitonin is more stable than the human form because of its greater hydrophobicity.
After opening
Once opened, the nasal spray is switched to 2-8°C storage. Injectable presentations continue to be kept at 2-8°C throughout use. The greater stability of salmon calcitonin compared with the human peptide carries over to the opened product as well.
Section 07
Side Effects & Precautions
Calcitonin's reported effects differ by route of administration (nasal spray versus injection), and long-term use has been linked to a slightly increased cancer risk that limits the recommended treatment duration.
Effects with nasal use
Nasal use has been linked to rhinitis, an inflamed and runny nose (12%), nosebleeds (epistaxis), and nasal irritation.
Effects with injection
Injection has been linked to nausea (10%), facial flushing, and reactions at the injection site.
Long-term cancer risk warning
Long-term use has been associated with a slightly increased cancer risk, per a warning from the European Medicines Agency (EMA). This limits the recommended treatment duration to under 2 years.
Section 08
Regulatory Status
FDA / United States
Approved for three specific conditions
Miacalcin and Fortical covered postmenopausal osteoporosis (second-line), Paget's disease of bone and hypercalcemia. Both nasal-spray brands were discontinued for commercial reasons, but generic calcitonin-salmon injection remains on the market from other manufacturers.
EMA / Europe
Restricted sharply after a cancer signal
A 2012 review found a small but real increase in cancer risk with long-term use. The CHMP withdrew the osteoporosis indication entirely, limited calcitonin to short-term injectable use for Paget's disease, acute immobilisation bone loss and cancer-related hypercalcemia, and removed the nasal spray from the EU market.
WADA
Not prohibited
Calcitonin does not appear in the peptide-hormone (S2) or hormone-and-metabolic-modulator (S4) sections of the 2026 Prohibited List, so athletes may use it without a therapeutic use exemption.
Regulatory status differs by country and changes over time. The EU withdrew calcitonin's osteoporosis indication in 2012 while the US retained it — check the label that applies in your own jurisdiction.
Section 09
Research Studies
- [1]Phase-plate cryo-EM structure of a class B GPCR-G-protein complexLiang YL, Khoshouei M, Radjainia M, et al. · Nature · 2017
- [2]Molecular pharmacology of the calcitonin receptorPurdue BW, Tilakaratne N, Sexton PM. · Receptors and Channels · 2002
- [3]Multiple amylin receptors arise from receptor activity-modifying protein interaction with the calcitonin receptor gene productChristopoulos G, Perry KJ, Morfis M, et al. · Molecular Pharmacology · 1999
- [4]Calcitonin alters behaviour of isolated osteoclastsChambers TJ, Magnus CJ. · The Journal of Pathology · 1982
- [5]Evidence that the action of calcitonin on rat osteoclasts is mediated by two G proteins acting via separate post-receptor pathwaysZaidi M, Datta HK, Moonga BS, MacIntyre I. · Journal of Endocrinology · 1990
- [6]Calcitonin induces dephosphorylation of Pyk2 and phosphorylation of focal adhesion kinase in osteoclastsZhang Z, Neff L, Bothwell AL, Baron R, Horne WC. · Bone · 2002
- [7]Calcitonin and Bone Physiology: In Vitro, In Vivo, and Clinical InvestigationsXie J, Guo J, Kanwal Z, et al. · International Journal of Endocrinology · 2020
- [8]Downregulation of calcitonin receptor mRNA expression by calcitonin during human osteoclast-like cell differentiationTakahashi S, Goldring S, Katz M, et al. · Journal of Clinical Investigation · 1995
- [9]Calcitonin induces expression of the inducible cAMP early repressor in osteoclastsYang M, Kream BE. · Endocrine · 2008
- [10]Calcitonin is a major regulator for the expression of renal 25-hydroxyvitamin D3-1alpha-hydroxylase gene in normocalcemic ratsShinki T, Ueno Y, DeLuca HF, Suda T. · Proceedings of the National Academy of Sciences · 1999
- [11]Calcitonin as an analgesic agent: review of mechanisms of action and clinical applicationsYazdani J, Khorshidi Khiavi R, Ghavimi MA, et al. · Brazilian Journal of Anesthesiology · 2019
Section 10
Frequently Asked Questions
In the pivotal nasal-spray trial (1,255 women followed for five years), only the 200 IU/day dose reduced vertebral fracture risk, by 33%, while 100 IU and 400 IU did not show the same effect. It has been largely superseded by bisphosphonates and denosumab, but it retains a role for pain relief after acute vertebral fractures, where an analgesic benefit appears within days.
The nasal spray causes rhinitis in about 12% of users, plus nasal irritation and occasional nosebleeds; injections more often cause nausea (about 10%) and facial flushing. The EMA identified a cancer signal with long-term use — malignancy rates ran 0.7 to 2.4 percentage points above placebo in pooled data — and responded by limiting recommended treatment duration to under two years and withdrawing the nasal spray from the European market in 2012.
Calcitonin down-regulates its own receptor: in cultured human osteoclast-like cells, exposure to calcitonin reduced calcitonin receptor mRNA within 12 hours, and the drug-stimulated rise in cAMP fell in parallel, recovering once the hormone was removed. This receptor down-regulation, mediated partly by an inducible repressor called ICER, underlies calcitonin's well-documented "escape" from effect during continued use.
They are different hormones. Calcitonin comes from the thyroid's C-cells and inhibits osteoclast-driven bone resorption, helping maintain calcium homeostasis. The source material doesn't lay out parathyroid hormone's own mechanism in full, but it documents one place the two intersect: in rats, calcitonin injection sharply raised the kidney's vitamin-D-activating enzyme (CYP27B1), while parathyroid hormone only did so in animals that were already vitamin-D-deficient.
Doses vary by route and use: 200 IU/day nasal spray for osteoporosis, 100 IU/day by injection for Paget's disease or postmenopausal osteoporosis, and much higher hospital doses (4-8 IU/kg every 6-12 hours) for emergency treatment of high blood calcium. For acute immobility-related bone loss, the EU label caps injectable use at four weeks — a regulatory limit tied to the cancer signal seen with longer use rather than a biological one — and repeat courses were never approved.
It depends on the form. The nasal spray is kept at room temperature (up to 25°C) before opening but switches to 2-8°C refrigeration once opened, while injectable calcitonin is kept refrigerated at 2-8°C throughout, both before and during use.
No — WADA does not prohibit calcitonin. It is FDA-approved for osteoporosis, Paget's disease and hypercalcemia, but the EMA has restricted its use to short courses because of the cancer signal seen with prolonged treatment, so approval here comes with a duration limit rather than being unconditional.