Should romosozumab be used in patients with a history or risk of CVD?

Romosozumab offers substantial fracture protection, but its use in patients with cardiovascular disease or risk factors for cardiovascular disease remains uncertain. Randomized trials have yielded conflicting cardiovascular findings, and meta-analyses have not definitively excluded clinically relevant harm. Observational studies generally report no increased risk compared with other osteoporosis treatments, including in some patients with previous cardiovascular events. However, these findings are limited by treatment-selection bias, heterogeneous outcome definitions, and relatively short follow-up. Thus, in patients with established cardiovascular disease, a potential risk remains biologically plausible but unproven. Careful patient selection is still required, and individuals with established cardiovascular disease should be excluded based on US and European labeling advice. More studies are still needed to understand the basic biology of sclerostin relative to atherosclerosis and vessel calcification.