Etodolac: efficacy in osteoarthritis and effects on chondrocyte function

Abstract

Some nonsteroidal anti-inflammatory drugs (NSAIDs) used in the treatment of osteoarthritis (OA) may damage articular cartilage. This damage may be caused by suppression of proteoglycan synthesis or by altered collagen synthesis in the presence of prostaglandin E2 (PGE2) induced by interleukin-1 (IL-1). The clinical and biochemical effects of etodolac, a new NSAID, on the symptoms of OA and on cartilage metabolism are reviewed. Clinically, etodolac (200-600 mg/day) was more effective than placebo, and as effective as aspirin (3200-4800 mg/day), piroxicam (20 mg/day), naproxen (1000 mg/day), and diclofenac (150 mg/day) in relieving the symptoms of OA. In in vitro studies, proteoglycan synthesis was not affected by the presence of etodolac when human chondrocytes were grown in a three-dimensional culture. Etodolac preserved collagen phenotype in human chondrocytes cultured in a monolayer in the presence of IL-1. In contrast, the collagen phenotype of cells cultured in the presence of indomethacin and IL-1 changed. Under those conditions, less type II and type IX collagen were synthesized and more type I and type III collagen were synthesized. These findings suggest that etodolac, an effective agent in the treatment of OA, has the potential advantage of not damaging articular cartilage in vivo.