Calcitonin Gene-Related Peptide (CGRP)
Overview
Calcitonin gene-related peptide is a 37-amino acid neuropeptide produced by alternative splicing of the calcitonin gene. CGRP acts as a potent vasodilator and plays a key role in migraine pathophysiology by binding to CGRP receptors on vascular smooth muscle and trigeminal nerve endings. While CGRP itself has effects on bone metabolism through regulation of osteoblast and osteoclast activity, therapeutic development has focused primarily on antagonizing CGRP signaling rather than administering the peptide. The peptide's role in bone includes modulation of bone formation and vascular coupling in skeletal tissue.
Key Research Findings
CGRP antagonists (gepants) and monoclonal antibodies targeting CGRP or its receptor have demonstrated efficacy in migraine prevention and treatment across multiple phase 3 trials. Research on CGRP's direct bone effects comes primarily from rodent models showing that CGRP-deficient mice exhibit altered bone density and that local CGRP administration can influence fracture healing. Clinical evidence for exogenous CGRP use in bone disorders remains limited, with most translational interest centered on understanding potential skeletal effects of CGRP-blocking therapies.
Intravenous, Subcutaneous injection
Research Phase
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Teriparatide (Forteo)
FDA ApprovedA recombinant form of the first 34 amino acids of human parathyroid hormone (PTH 1-34). When administered intermittently via daily subcutaneous injection, teriparatide stimulates osteoblastic bone formation more than osteoclastic resorption, producing a net anabolic effect on bone. It activates the PTH1 receptor on osteoblasts, increasing Wnt signaling, osteoblast differentiation, and survival while reducing sclerostin expression.
Abaloparatide (Tymlos)
FDA ApprovedA synthetic 34-amino acid peptide analog of parathyroid hormone-related protein (PTHrP 1-34) that selectively activates the RG conformation of the PTH1 receptor. This receptor selectivity produces a more transient signaling response compared to teriparatide, favoring anabolic bone formation with less stimulation of bone resorption and calcium mobilization. Abaloparatide increases bone mineral density at both cortical and trabecular sites.
Calcitonin
FDA ApprovedA 32-amino acid peptide hormone naturally produced by parafollicular C-cells of the thyroid gland. Calcitonin inhibits osteoclast-mediated bone resorption by binding to calcitonin receptors on osteoclasts, reducing their activity and number. Salmon calcitonin is approximately 40-50 times more potent than human calcitonin and has a longer half-life, making it the preferred therapeutic form.
Vosoritide (Voxzogo)
FDA ApprovedA C-type natriuretic peptide (CNP) analog that acts as an agonist at the natriuretic peptide receptor B (NPR-B) on growth plate chondrocytes. Vosoritide counteracts the constitutively activated FGFR3 signaling that suppresses endochondral ossification in achondroplasia. By stimulating the NPR-B/cGMP/MAPK pathway, it antagonizes the growth-inhibitory FGFR3 signal and restores more normal linear bone growth.