Is there preliminary in-vivo evidence for an influence of nonsteroidal antiinflammatory drugs on progression in osteoarthritis? Part II—evidence from animal models

Abstract

SINCE Ho#man synthesized aspirin (ASA), more than 100 years ago, there is a general agreement that nonsteroidal antiinflammatory drugs (NSAIDs) provide symptomatic relief for millions of people with osteoarthritis (OA). The role of NSAIDs became confused with the discovery that some R-enantiomers of the profenic group of NSAIDs were as e#ective as S-series enantiomers in relieving pain in OA. This was despite the fact that the R-enantiomeres were several hundred fold less active in inhibiting prostaglandin (PG) synthesis and ine#ective in animal models of inflammation. The value of NSAIDs in OA became further confused with the frequency of adverse reactions (particularly in the elderly) and reports of rapid destructive arthropathy in patients taking high doses of indomethacin. Consequently, Brandt (1993) published a sharp review with an intriguing title: ‘Should OA be treated with NSAID?’ We do not yet fully understand the etiopathogenesis of OA and the mechanism of NSAIDs activity on the intrinsic and migrating cells of the joint. What is known is controversial and filled with personal opinions. Animal models have been of some help in defining these processes. If we are to assume that NSAIDs are e#ective in providing symptomatic relief and that NSAIDs have analgesic as well as anti-inflammatory properties, we can pose the following questions: (1) what is the evidence that OA is an inflammatory joint disease and (2) what is the evidence that the joint pain in OA is due to synovitis?