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Knee osteoarthritis (OA) is the most common form of OA and a leading cause of disability worldwide. Chronic pain and functional loss secondary to knee OA put patients at risk of developing depression, which can also impair their treatment response. However, no tools exist to assist clinicians in identifying patients at risk. Machine learning (ML) predictive models may offer a solution. We investigated whether ML models could predict the development of depression in patients with knee OA and examined which features are the most predictive.