These data allow us to hypothesize that NSAIDs, by inhibiting pain and inflammation in osteoarthritic joints, may cause or encourage people with OA to overuse damaged joints, resulting in accelerated joint degeneration and joint replacements at an earlier time or, alternatively, that treatment with NSAIDs may accelerate joint damage by altering cartilage metabolism and inhibiting joint healing. We further hypothesize that anti-inflammatory therapy with NSAIDs results in toxicities that lead to increased comorbidity and higher medical care use compared to analgesic therapy for OA.