Cardiovascular Safety and Sclerostin Inhibition – a mini-rev
Now open: Certificate Course in Management of Covid-19 by Govt. Of Gujarat and PlexusMDKnow more...Now open: Certificate Course in Management of Covid-19 by Govt. Of Gujarat and PlexusMDKnow more...
Sclerostin is primarily produced by the osteocytes, inhibits the canonical Wnt pathway and thereby the osteoblasts, and stimulates RANKL release by the osteocytes and thereby osteoclast recruitment. Inhibition of sclerostin therefore causes stimulation of bone formation and inhibition of resorption. In clinical trials romosozumab, an antibody against sclerostin, increases BMD and reduces the risk of fractures compared to placebo and alendronate.

The cardiovascular safety of romosozumab was adjudicated in 2 large clinical osteoporosis trials in postmenopausal women. Compared with placebo, the incidence of cardiovascular events was similar in the two treatment groups. Compared to alendronate, the incidence of serious cardiovascular events was higher in women treated with romosozumab. The incidence of serious cardiovascular adverse events was low and posthoc analyses should therefore be interpreted with caution, however, the relative risk seemed unaffected by preexisting cardiovascular disease or risk factors.

Sclerostin is expressed in the vasculature, predominantly in vascular smooth muscle cells in the media. However, preclinical and genetic studies have not demonstrated any increased cardiovascular risk with continuously low sclerostin levels or inhibition of sclerostin. Furthermore, no potential mechanisms for such an effect have been identified.

In conclusion, while there is no preclinical or genetic evidence of a harmful effect of sclerostin inhibition on cardiovascular safety, the evidence from the large clinical trials in postmenopausal women is conflicting. Romosozumab should therefore be used for the treatment of postmenopausal women with osteoporosis at high risk of fracture after careful consideration of the cardiovascular risk and the balance between benefits and risks.

Source: https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/clinem/dgab193/6182322?redirectedFrom=fulltext
Like
Comment
Share