Pathogenetisch orientierte Therapieansätze bei der Osteoarthrose – Sind DMOADs in der Pipeline?

Zusammenfassung

Die Osteoarthrose (OA) ist im Gegensatz zur rheumatoiden Arthritis eine primär degenerative Gelenkerkrankung. Neue Erkenntnisse zeigen allerdings, dass die OA keine rein passive Verschleißerkrankung ist, sondern ein aktiver Prozess, der auf einem komplexen Zusammenspiel der 3 Kompartimente des Gelenkknorpels, -knochens und -synoviums beruht. Die Knorpelmatrix geht durch Veränderungen in der Knorpelhomöostase verloren. Der Knochen und die Synovialmembran verdicken sich und pro-inflammatorische Zytokine führen zu rezidivierenden Entzündungsschüben, die auf alle 3 Kompartimente zurück wirken und zum letztendlichen Funktionsverlust des Gelenks führen. Dennoch ist die OA ganz klar von der rheumatoiden Arthritis zu unterscheiden, welche auch zum Funktionsverlust des Gelenks führt, die aber primär entzündlich ist. Versucht man aktuelle Strategien, krankheitsmodifizierende, also disease modifying OA drugs (DMOADs) für die OA zu entwickeln, so kann man die 3 oben beschriebenen Kompartimente als Ansatzpunkte wiedererkennen. Ausgehend von den bestehenden, legt dieser Artikel den Fokus auf neue Therapiestrategien zur Behandlung der OA sowie deren Mechanismen, welche primär auf den Knorpel, den Knochen sowie die Synovialmembran abzielen. Viele dieser Therapiestrategien sind im Tiermodell vielversprechend, es bleibt aber für die meisten Ansätze weiter offen, inwieweit sich diese ersten Ergebnisse auf den Menschen übertragen lassen.

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.

Schlüsselwörter

Osteoarthrose - Knorpel - Knochen - Synovium - Therapie

Key words

osteoarthritis - cartilage - bone - synovium - therapy

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