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Osteoarthritis (OA) is a chronic degenerative joint disease associated with pain, inflammation, and cartilage degradation. However, no current treatment can effectively halt the progression of the disease. Therefore, the use of NSAIDs and intra-articular corticosteroids is usually recommended as the primary treatment for OA-associated pain and inflammation. However, there is accumulating evidence that the long-term use of oral NSAIDs and intra-articular corticosteroids can lead to a myriad of negative side effects. Although numerous efforts have been made to develop intra-articular formulations for NSAIDs, the systemic exposure of intra-articular injection of NSAIDs and its potential side effects have not been explicitly investigated. To ascertain the evident and potential side effects of intra-articular injection of anti-inflammatory agents, we have summarised in this review the systemic exposure, local side effects, and …