Calcitonin

In simple words

Calcitonin is a hormone that slows the breakdown of bone; the salmon version is dozens of times more active than the human one. It is approved for osteoporosis and Paget's disease, and in studies it reduced pain from vertebral compression fractures.

What this molecule is

32 amino acids. Cys1-Cys7 disulfide bond. C-terminal prolinamide. Salmon vs human: 16 substitutions → 40–50 times higher activity. ~3432 Da.

Why it is studied

FDA-approved (Miacalcin): postmenopausal osteoporosis, Paget's disease, hypercalcemia. NNT=2 for pain from vertebral compression fractures (effect by week 1). Nasal spray.

How it works

Calcitonin receptor (CTR, class B GPCR) on osteoclasts → ↓bone resorption (↓TRAP, ↓cathepsin K). Neuronal mechanism: ↑β-endorphin → analgesia (hence the effect in fractures). ↓renal Ca²⁺ reabsorption → ↓hypercalcemia.

Doses used in studies

Studies used nasal spray 200 IU/day (alternating nostrils). For fracture pain — 200 IU nasally or 100 IU SC daily, for 2–4 weeks. For hypercalcemia — 4–8 IU/kg every 12 h.

Combined with in studies

• Vitamin D3 + calcium — standard combination
• Bisphosphonates — different mechanisms
• BPC-157 — bone regeneration + GI tract

Level of evidence

Level A Human clinical trials. There are randomized controlled trials (RCTs), or the compound has been approved by a regulatory agency. The most reliable level. FDA-approved 1995. Meta-analyses.

Important to know

Honest caveat: The EMA withdrew the nasal form (2012) because of a cancer-risk signal with long-term use (a causal link has not been confirmed, PMID: 26438308). Only short-term, for pain. Not first-line for osteoporosis.

Studies in PubMed

1. Efficacy of calcitonin for treating acute pain associated with osteoporotic vertebral compression fracture: an updated systematic review. (CJEM, 2020)
2. A meta-analysis of the therapeutic effect of intranasal salmon calcitonin on osteoporosis. (Eur J Med Res, 2021)
3. A phase 3 trial of the efficacy and safety of oral recombinant calcitonin: the Oral Calcitonin in Postmenopausal Osteoporosis (ORACAL) trial. (J Bone Miner Res, 2012)
4. Evaluation of the efficacy of salmon calcitonin nasal spray on bone healing following open reduction and internal fixation of mandibular fractures - A randomized controlled trial. (J Craniomaxillofac Surg, 2021)
5. Does salmon calcitonin cause cancer? A review and meta-analysis. (Osteoporos Int, 2016)
6. Effectiveness and Safety of Treatments to Prevent Fractures in People With Low Bone Mass or Primary Osteoporosis: A Living Systematic Review and Network Meta-analysis for the American College of Physicians. (Ann Intern Med, 2023)