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

Targeted inhibition of sclerostin for post-menopausal osteoporosis therapy: a critical assessment of the mechanism of action.
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Bhattacharyya S, Pal S, Chattopadhyay N,


Bhattacharyya S, Pal S, Chattopadhyay N, (click to view)

Bhattacharyya S, Pal S, Chattopadhyay N,

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European journal of pharmacology 2018 02 21() pii S0014-2999(18)30106-7
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 clinical practice. For example, neutralizing sclerostin alters calcium homeostasis and increases PTH. In addition, sclerostin depletion in preclinical studies has been reported to severely compromises B cell depletion in bone marrow. We have reviewed the currently available evidences that support the use of sclerostin antibody in treating osteoporosis and compare its efficacy and mechanism of action with the currently available anabolic drug, human PTH.

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