Rationale for the use of structure-modifying drugs and agents in the treatment of osteoarthritis.

This paper summarizes our current stand on potential pathophysiological targets for osteoarthritis (OA) therapies. Although OA is a complicated disease, involving the cartilage, synovial membrane, and subchondral bone, a number of interactive pathways have been found to explain the structural changes in the disease process. Study of these three tissues has yielded a list of targets to examine for their potential to affect disease progression. At the cartilage level, therapeutic agents, such as growth factors, could be targeted to increase chondrocyte anabolism. At the synovial level, cytokines and cytokine receptor antagonists are potential targets for therapy. In the subchondral bone, cytokines, growth factors and eicosanoids, and locally synthesized factors affecting bone metabolism are also potential targets of therapy. Recent progress in the understanding of the pathophysiology of OA has led to exploration of several interesting new approaches toward the treatment of this disease. New classes of molecules that inhibit one or more OA disease processes are under evaluation for their potential to alter the degenerative process. The prospect of finding a cure for OA is more promising than ever. Based on the discovery of major pathophysiological pathways leading to the structural changes observed in OA, novel ways to treat the progression of OA lesions are emerging.