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Mediterranean Journal of Medical Research
https://mrj.org.ly/article/doi/10.5281/zenodo.19949507

Mediterranean Journal of Medical Research

Review Pharmacology

Targeting the Wnt/β-catenin axis through sclerostin inhibition in postmenopausal osteoporosis: Translational advances and safety perspectives

Nousheen, Fathima, Karunakar Hegde

http://dx.doi.org/10.5281/zenodo.19949507 Mediterr J Med Res, vol.3, n2, p.152-161, 2026
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Abstract

Post menopausal osteoporosis is a chronic metabolic bone disorder characterised by decreased bone mineral density and increased risk of fracture due to estrogen deficiency. This estrogen deficiency will reduce osteogenesis and increase osteoclast-mediated bone resorption, leading to an imbalance in bone remodelling. The Wnt/β-catenin signalling pathway plays an important role in regulating bone formation by promoting osteoblast differentiation and inhibiting resorption. Sclerostin, produced by osteocytes, inhibits and binds to LRP5/6 co-receptors in this pathway and suppresses bone formation. This review summarises the molecular mechanisms of Wnt/β-catenin signalling and the role of sclerostin in the pathogenesis of postmenopausal osteoporosis. It also explains recent therapeutic advances in anti-sclerostin therapy, such as Romosozumab, which restores Wnt signalling by enhancing bone formation and reducing bone resorption. Various clinical studies suggested a significant increase in bone mineral density and a reduction in fracture risk, but these are also associated with cardiovascular effects like stroke and myocardial infarction. Future research should focus on biomarker-guided therapy, precision medicine, and novel Wnt pathway modulators to optimise treatment efficacy and safety in the management of postmenopausal osteoporosis.

Keywords

Bone remodelling, postmenopausal osteoporosis, sclerostin, Wnt/β-catenin signalling pathway

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Submitted date:
02/25/2026

Reviewed date:
04/15/2026

Accepted date:
04/22/2026

Publication date:
05/01/2026

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