Sclerostin and Cardiovascular Disease

Area of Science:

• Cardiovascular research
• Endocrinology
• Pharmacology

Background:

• Wnt signaling plays a role in atherogenesis.
• Sclerostin, a Wnt inhibitor, may offer natural protection against atherosclerosis.
• Anti-sclerostin antibodies could potentially elevate atherosclerosis and cardiovascular disease (CVD) risk.

Purpose of the Study:

• To evaluate the potential adverse effects of sclerostin inhibition on CVD risk.
• To triangulate evidence from various sources regarding sclerostin inhibition and CVD.

Main Methods:

• Review of randomized controlled trials (RCTs) of romosozumab.
• Analysis of three Mendelian randomization (MR) studies using genetic variants in the SOST gene.
• Triangulation of evidence from RCTs and MR studies.

Main Results:

• Conflicting evidence exists regarding romosozumab's effects on CVD risk.
• Two MR studies indicated that sclerostin lowering increases the risk of myocardial infarction (MI) and type II diabetes mellitus.
• One study suggested sclerostin lowering is associated with increased coronary artery calcification.

Conclusions:

• Evidence suggests sclerostin lowering may increase MI risk.
• Cardiovascular disease risk assessment is crucial when using romosozumab.
• Further research may be needed to fully elucidate the CVD risks associated with sclerostin inhibition.