Cardiovascular Safety and Sclerostin Inhibition

Abstract Sclerostin, which is primarily produced by the osteocytes, inhibits canonical Wnt pathway and thereby osteoblasts stimulates RANKL release osteocytes osteoclast recruitment. Inhibition of sclerostin therefore causes stimulation bone formation inhibition resorption. In clinical trials, romosozumab, an antibody against sclerostin, increases mineral density reduces risk fractures compared with placebo alendronate. The cardiovascular safety romosozumab was adjudicated in 2 large osteoporosis trials postmenopausal women. Compared placebo, incidence events similar treatment groups. alendronate, serious higher women treated romosozumab. adverse low post hoc analyses should be interpreted caution; however, relative seemed unaffected preexisting disease or factors. Sclerostin expressed vasculature, predominantly vascular smooth muscle cells media. However, preclinical genetic studies have not demonstrated any increased continuously levels sclerostin. Furthermore, no potential mechanisms for such effect been identified. conclusion, while there evidence a harmful on safety, from conflicting. Romosozumab used at high fracture after careful consideration balance between benefits risks.