Targeted inhibition of sclerostin for post-menopausal osteoporosis therapy: A critical assessment of the mechanism of action

European Journal of Pharmacology
Sharmistha BhattacharyyaNaibedya Chattopadhyay

Abstract

Promising news in the treatment of osteoporosis is that sequestering sclerostin from circulation with antibodies stimulates robust bone formation. Pre-clinical studies on rodents and monkeys have confirmed that treatment with anti-sclerostin monoclonal antibody (Scl-Ab) increases bone mass, improves bone strength and enhances fracture repair. Clinical trials show that bone gain (anabolic effect) is transient and are primarily at central (spine and hips) than peripheral (wrist) sites. Interestingly Scl-Ab also inhibited bone resorption. Thus Scl-Ab is being regarded as the pharmacologic agent with dual properties - stimulating bone formation and decreasing bone resorption. Sclerostin neutralization transiently increases bone formation markers in post-menopausal women and like parathyroid hormone (PTH) activates osteoblasts and lining cells resulting in bone anabolic effect. However, unlike PTH, sclerostin antibody also decreases bone resorption (anti-catabolic). Although, the U.S. Food and Drug Administration have accepted the Biologics License Application for one of the monoclonal antibodies against sclerostin (romosozumab) for review, many questions remain before romosozumab can be introduced as a skeletal anabolic agent to cl...Continue Reading

Citations

Dec 11, 2019·The Journal of Clinical Endocrinology and Metabolism·Zafer PekkolayAlpaslan Kemal Tuzcu
Jan 28, 2020·International Journal of Molecular Medicine·Qiushi WeiYanming Cao
Apr 25, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Basem M Abdallah, Enas M Ali
Nov 3, 2020·Biochemical Pharmacology·Hui WangAimin Wu
Aug 1, 2019·Current Medicinal Chemistry·Massimo De MartinisLia Ginaldi

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