Denosumab in osteoarthritis: from mechanism to clinical translation

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Osteoarthritis affects over 600 million people globally, yet no disease-modifying drugs have been approved to alter its progression.
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Denosumab, a monoclonal antibody targeting RANKL, shows promise as a potential disease-modifying osteoarthritis drug based on preclinical and clinical evidence.
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Denosumab disrupts inflammatory pathways in osteoarthritis by blocking RANKL signaling, which reduces pro-inflammatory mediators and macrophage activation.
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A phase 2a trial demonstrated that denosumab significantly improved joint function and reduced erosive joint progression in patients with erosive hand osteoarthritis.
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Long-term safety and efficacy of denosumab in non-osteoporotic osteoarthritis patients require further investigation through larger multicenter studies.

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