Abstract
Purpose of Review
The role of wnt signalling in atherogenesis raises the possibility that the wnt inhibitor, sclerostin, provides a natural defence to this process, and that anti-sclerostin antibodies might increase the risk of atherosclerosis and associated conditions such as CVD. This article aims to triangulate evidence concerning possible adverse effects of sclerostin inhibition on CVD risk.
Recent Findings
Randomised controlled trials of treatment with the anti-sclerostin antibody, romosozumab, have yielded conflicting evidence with respect to possible adverse effects of sclerostin inhibition on CVD risk. To further examine the causal relationship between sclerostin inhibition and CVD risk, three Mendelian randomisation (MR) studies have examined effects of sclerostin lowering on CVD outcomes, using common genetic variants in the SOST gene which produces sclerostin, to mimic effects of a randomised trial. Concordant findings were seen in two studies, comprising an effect of sclerostin lowering on increased risk of MI and type II diabetes mellitus. One study also suggested that sclerostin lowering increases coronary artery calcification.
The role of wnt signalling in atherogenesis raises the possibility that the wnt inhibitor, sclerostin, provides a natural defence to this process, and that anti-sclerostin antibodies might increase the risk of atherosclerosis and associated conditions such as CVD. This article aims to triangulate evidence concerning possible adverse effects of sclerostin inhibition on CVD risk.
Recent Findings
Randomised controlled trials of treatment with the anti-sclerostin antibody, romosozumab, have yielded conflicting evidence with respect to possible adverse effects of sclerostin inhibition on CVD risk. To further examine the causal relationship between sclerostin inhibition and CVD risk, three Mendelian randomisation (MR) studies have examined effects of sclerostin lowering on CVD outcomes, using common genetic variants in the SOST gene which produces sclerostin, to mimic effects of a randomised trial. Concordant findings were seen in two studies, comprising an effect of sclerostin lowering on increased risk of MI and type II diabetes mellitus. One study also suggested that sclerostin lowering increases coronary artery calcification.
Original language | English |
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Pages (from-to) | 519-526 |
Number of pages | 8 |
Journal | Current Osteoporosis Reports |
Volume | 21 |
Issue number | 5 |
Early online date | 25 Jul 2023 |
DOIs | |
Publication status | Published - 1 Oct 2023 |
Bibliographical note
Funding Information:I am grateful to Professor Emma Clark, Professor Celia Gregson and Professor George Davey Smith for their comments on the manuscript.
Publisher Copyright:
© 2023, The Author(s).