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OA is increasingly recognized as a whole-joint disorder characterized by complex biochemical and cellular changes across various joint tissues. However, traditional approaches such as nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids often fall short in halting disease progression or restoring joint function. Thereby, recent innovations in OA management are focused on underlying pathophysiology, driving the development of regenerative therapies, targeted anti-inflammatory agents and senolytic or senomorphic approaches. Accordingly, this paper reviews current progress in these areas by integrating evidence from clinical and pre-clinical studies to clarify therapeutic limitations, unresolved mechanistic and phenotypic gaps and the emerging strategies required to advance disease-modifying therapy in OA. 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