Romosozumab
Anti-sclerostin antibody that stimulates bone formation and inhibits resorption for severe osteoporosis treatment.
Chemical Identity
| Property | Value |
|---|---|
| Molecular Weight | ~147 kDa |
| CAS Number | 945782-86-3 |
| Peptide Class | Humanized IgG2 Monoclonal Antibody |
| Target | Sclerostin |
| Route | SC injection |
Structure
Romosozumab (Evenity) is a humanized IgG2 monoclonal antibody that binds and inhibits sclerostin, a glycoprotein secreted by osteocytes that negatively regulates the Wnt signaling pathway in osteoblasts.
Mechanism of Action
Sclerostin inhibits Wnt signaling by binding LRP5/6 co-receptors on osteoblasts, suppressing bone formation. Romosozumab neutralizes sclerostin, de-repressing Wnt signaling and stimulating osteoblast differentiation, proliferation, and activity. This dual effect increases bone formation while decreasing bone resorption.
Clinical Applications
- Postmenopausal osteoporosis: High fracture risk (Evenity)
- Male osteoporosis: High fracture risk
- Glucocorticoid-induced osteoporosis: Severe cases
- Treatment sequencing: Before anti-resorptive to maintain gains
Pharmacokinetics
- Half-life: 12.8 days
- Tmax: 5 days (SC)
- Bioavailability: 61%
- Dosing: 210 mg SC monthly for 12 months
- Route: SC injection
Safety and Side Effects
Injection site reactions, headache, arthralgia, hypocalcemia, and potential cardiovascular risk (increased MACE in FRAME trial). Contraindicated in patients with MI or stroke within 1 year. 12-month treatment limit recommended.
References
- Cosman, F., et al. (2016). FRAME trial: romosozumab for osteoporosis. New England Journal of Medicine, 375, 1532-1543.
- Saag, K.G., et al. (2017). ARCH trial: romosozumab followed by alendronate. New England Journal of Medicine, 377, 1417-1427.
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