New Insights into Bone Loss in RA

Abstract

The negative impact of rheumatoid arthritis (RA) on bone mineral density is well characterized. Notably, articular bone erosion is a central feature of RA, leading to joint damage and disabilities. In addition, the axial and appendicular skeleton can be affected, which secondly manifests in bone fracture. The main trigger of RA-associated bone loss is excessive bone degradation by osteoclasts and impaired bone formation by osteoblasts. In particular, the inflammatory status, reflected by high level of proinflammatory cytokines, receptor activator of nuclear factor κB ligand (RANKL), and autoantibodies induces the formation of bone-resorbing osteoclasts. Today, antirheumatic therapy effectively hampers synovial inflammation and bone erosion. However, current medication is unable to repair established bone lesions. This review outlines the knowledge gained about the pathophysiology of rheumatoid arthritis and the molecular mechanisms that promote osteoclast-mediated bone erosion and inhibit osteoblast-related bone formation, pointing out possible new intervention for inflammatory bone disease.

Zusammenfassung

Negative Auswirkungen der rheumatoiden Arthritis (RA) auf die Knochendichte werden in vielen Patienten beobachtet. Insbesondere Knochenerosionen im Gelenk sind ein zentrales Merkmal von RA, was in der Regel zu Gelenksschädigung und Bewegungseinschränkungen führt. Darüber hinaus können auch das axiale und appendikuläre Skelett betroffen sein, was im weiteren Verlauf Knochenbrüche verursachen kann. Die Hauptursache für RA-assoziierten Knochenverlust ist ein übermäßiger Knochenabbau durch Osteoklasten und ein beeinträchtigter Knochenaufbau durch Osteoblasten. Entzündliche Faktoren wie proinflammatorische Zytokine, receptor activator of nuclear factor κB ligand (RANKL) und Autoantikörper begünstigen v. a. die Bildung von knochenresorbierenden Osteoklasten. Die heutzutage verordnete antirheumatische Medikation hemmt effektiv die Gelenksentzündung und den Knochenabbau. Allerdings sind die derzeitigen Medikamente nicht in der Lage, bereits entstandene Knochenläsionen zu reparieren. Dieser Übersichtsartikel beschreibt die bisher gewonnenen Erkenntnisse über die Pathophysiologie der rheumatoiden Arthritis und die molekularen Mechanismen, die einerseits die Osteoklasten-vermittelte Knochenerosion induzieren und andererseits zu einer Hemmung der Knochenneubildung durch Osteoblasten führen. Es werden mögliche neue Therapieansätze betrachtet, die insbesondere die knochenschädigende Auswirkung von RA aufheben sollen.

Key words

Rheumatoid arthritis - bone erosion - Osteoclasts - Osteoblasts

Schlüsselwörter

Rheumatoide Arthritis - Knochenerosion - Osteoklasten - Osteoblasten

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