Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics
Jonas Bovijn, Kristi Krebs, Chia‐Yen Chen, Ruth Boxall, Jenny C. Censin, Teresa Ferreira, Sara L. Pulit, Craig A. Glastonbury, Samantha Laber, Iona Y. Millwood, Kuang Lin, Liming Li, Zhengming Chen, Lili Milani, George Davey Smith, Robin Walters, Reedik Mägi, Benjamin M. Neale, Cecilia M. Lindgren, Michael V. Holmes
Abstract
genetic variants were associated with lower risk of fracture and osteoporosis (commensurate with the therapeutic effect of romosozumab) and with a higher risk of myocardial infarction and/or coronary revascularization and major adverse cardiovascular events. The same variants were also associated with increased risk of type 2 diabetes mellitus and higher systolic blood pressure and central adiposity. Together, our findings indicate that inhibition of sclerostin may elevate cardiovascular risk, warranting a rigorous evaluation of the cardiovascular safety of romosozumab and other sclerostin inhibitors.