Research ArticleGenetics

Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics

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Science Translational Medicine  24 Jun 2020:
Vol. 12, Issue 549, eaay6570
DOI: 10.1126/scitranslmed.aay6570

Safety and sclerostin

Antibodies that inhibit sclerostin are used to treat osteoporosis because they increase bone mineral density and reduce fracture risk; however, phase 3 trials have identified potential cardiovascular safety concerns. Using meta-analysis, Bovijn and colleagues found probable higher risk of adverse cardiovascular events associated with sclerostin antibody use. Analysis of variants in SOST, the gene that encodes sclerostin, showed that variants associated with increased bone mineral density (mimicking the effects of therapeutic inhibition of sclerostin) were linked to cardiometabolic risk factors and disease. Results highlight the importance of evaluating the cardiovascular safety of sclerostin inhibition.

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