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  • Review Article
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Bone erosion in rheumatoid arthritis: mechanisms, diagnosis and treatment

Nature Reviews Rheumatology volume 8, pages 656–664 (2012)Cite this article

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Abstract

Bone erosion is a central feature of rheumatoid arthritis and is associated with disease severity and poor functional outcome. Erosion of periarticular cortical bone, the typical feature observed on plain radiographs in patients with rheumatoid arthritis, results from excessive local bone resorption and inadequate bone formation. The main triggers of articular bone erosion are synovitis, including the production of proinflammatory cytokines and receptor activator of nuclear factor κB ligand (RANKL), as well as antibodies directed against citrullinated proteins. Indeed, both cytokines and autoantibodies stimulate the differentiation of bone-resorbing osteoclasts, thereby stimulating local bone resorption. Although current antirheumatic therapy inhibits both bone erosion and inflammation, repair of existing bone lesions, albeit physiologically feasible, occurs rarely. Lack of repair is due, at least in part, to active suppression of bone formation by proinflammatory cytokines. This Review summarizes the substantial progress that has been made in understanding the pathophysiology of bone erosions and discusses the improvements in the diagnosis, monitoring and treatment of such lesions.

Key Points

  • Articular bone erosions are a central clinical feature of rheumatoid arthritis

  • Imaging techniques enable early detection of bone erosions and provide insights into disease pathogenesis

  • Bone erosion is a result of enhanced osteoclast differentiation and inhibition of osteoblast-mediated bone repair

  • Autoantibodies and cytokines, including proinflammatory cytokines and receptor activator of nuclear factor κB ligand, are the major precipitating factors in bone erosion in rheumatoid arthritis

  • Antirheumatic therapies block progression of bone erosion by mitigating synovial inflammation and restoring bone balance

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Figure 1: Autoantibodies against citrullinated proteins and osteoclastogenesis.
Figure 2: Evolution of bone erosion in the course of RA.
Figure 3: Site of action of antirheumatic drugs on osteoclast differentiation and bone erosion.
Figure 4: Disruption of bone homeostasis by synovitis.

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Acknowledgements

The work of G. Schett is supported by the Deutsche Forschungsgemeinschaft (SPP1468-IMMUNOBONE), the Bundesministerium f¨r Bildung und Forschung (BMBF; project ANCYLOSS) and the MASTERSWITCH project of the European Union and the IMI funded project BTCure. The work of E. Gravallese is supported by the NIH (R01 AR055952) and by the American College of Rheumatology Research and Education Foundation (Within our Reach: Finding a Cure for Rheumatoid Arthritis campaign).

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Authors and Affiliations

  1. Department of Internal Medicine 3, University of Erlangen-Nuremberg, Krankenhausstrasse 12, 91054, Erlangen, Germany

    Georg Schett

  2. Department of Medicine, University of Massachusetts Memorial Medical Center and University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, 01655, MA, USA

    Ellen Gravallese

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  1. Georg Schett
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Both authors contributed equally to all aspects of this article.

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Correspondence to Georg Schett.

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G. Schett declares no competing interests. E. Gravallese has acted as a consultant for Abbott Laboratories and has received grant/research support from Lilly.

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Schett, G., Gravallese, E. Bone erosion in rheumatoid arthritis: mechanisms, diagnosis and treatment. Nat Rev Rheumatol 8, 656–664 (2012). https://doi.org/10.1038/nrrheum.2012.153

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