Pathogenetic-Oriented Therapies for Osteoarthritis - Are New DMOADS on the Way?

Godmann L, Pap T, Bertrand J

Abstract

Osteoarthritis (OA), in comparison to rheumatoid arthritis (RA), is primarily a degenerative joint disease. New studies have revealed that OA is not a passive joint disease due to the constant wear, but constitutes an active process involving the 3 compartments of the joint: the cartilage, bone and synovium. The composition of the cartilage matrix changes and is lost due to complex changes in cartilage homeostasis. The thickness of the subchondral bone and the synovial membrane increases. Pro-inflammatory cytokines induce recurring inflammatory flares that affect all 3 compartments and lead to loss of joint function during the endstages of the disease. Nevertheless, OA has to be distinguished clearly from RA which, although is also characterised by the loss of joint function, in fact is primarily an inflammatory disease. Therefore, the development of new, disease-modifiying, strategies to treat OA using so-called disease-modifying OA drugs (DMOADs), exposes the 3 compartments described above as therapeutic starting points. Based on the existing evidence, this article focuses on new therapeutic strategies for the treatment of OA as well as the underlying pathways of action to affect one of the 3 compartments. Some of these strategies are promising in animal models, but their effectivity remains to be proven in humans.