The role of acetaminophen in the treatment of osteoarthritis.

The major clinical guidelines recommend the use of acetaminophen (acetyl-para-aminophenol [APAP]) for the treatment of mild-to-moderate symptoms of osteoarthritis (OA) and only recommend the use of nonsteroidal anti-inflammatory drugs (NSAIDs) after APAP failure. This recommendation is based on the efficacy of APAP in treating OA and its relatively benign side-effect profile compared with NSAIDs. NSAIDs are associated with a high risk of adverse events, particularly those of the gastrointestinal (GI) tract. A large number of studies in OA have compared APAP with a variety of selective and nonselective NSAIDs and typically found greater efficacy with NSAIDs. This advantage, however, is mainly the result of increased efficacy in patients with more severe disease, and is viewed as a relatively small analgesic advantage in some studies and meta-analyses. Many of these same studies have reported little or no difference in safety between APAP and NSAIDs, but these results are typically based on short-term studies. Results from meta-analyses on the safety of NSAIDs almost unanimously confirm elevated risk of GI complications. The analgesic mechanism of APAP is still not well understood. However, the notion that APAP has no anti-inflammatory effect has been challenged in recent years with increasing data that suggest it may have an effect on inflammation distinct from that seen with NSAIDs. A variety of mechanistic hypotheses have been proposed.