This study evaluates the efficacy and safety of denosumab, a receptor activator of nuclear factor-κB ligand inhibitor, in treating erosive hand osteoarthritis (OA). The randomized, placebo-controlled, double-blind phase 2a trial involved 100 patients with erosive hand OA, randomly assigned to receive either denosumab (60 mg every 3 months) or placebo for 48 weeks. The primary endpoint was the change in the total Ghent University Scoring System (GUSS) at week 24, with secondary endpoints including changes in GUSS at week 48 and the number of new erosive joints at week 48. The results showed that denosumab significantly reduced radiographic erosive progression and prevented new erosive joints compared to placebo, with no increased toxicity. Clinical outcomes, such as pain and disability, did not significantly change in the initial 48 weeks but showed improvement in the extension phase up to week 96. The study suggests that denosumab can modulate structural damage in erosive hand OA and may offer new treatment options for patients with this condition.This study evaluates the efficacy and safety of denosumab, a receptor activator of nuclear factor-κB ligand inhibitor, in treating erosive hand osteoarthritis (OA). The randomized, placebo-controlled, double-blind phase 2a trial involved 100 patients with erosive hand OA, randomly assigned to receive either denosumab (60 mg every 3 months) or placebo for 48 weeks. The primary endpoint was the change in the total Ghent University Scoring System (GUSS) at week 24, with secondary endpoints including changes in GUSS at week 48 and the number of new erosive joints at week 48. The results showed that denosumab significantly reduced radiographic erosive progression and prevented new erosive joints compared to placebo, with no increased toxicity. Clinical outcomes, such as pain and disability, did not significantly change in the initial 48 weeks but showed improvement in the extension phase up to week 96. The study suggests that denosumab can modulate structural damage in erosive hand OA and may offer new treatment options for patients with this condition.