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The balance of tissue repair and remodeling in chronic arthritis

Nature Reviews Rheumatology volume 7, pages 700–707 (2011)Cite this article

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Abstract

The introduction of targeted therapies has dramatically changed the prognosis of patients with chronic joint diseases such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS). As control of inflammation, and hence of symptoms of disease, is increasingly achieved, more attention is given towards the long-term consequences of these disorders, to the structural damage in the skeletal tissues and to the resulting disability. In AS, bone remodeling with new cartilage and bone formation leading to ankylosis is a striking feature. Clinically successful TNF antagonists do not inhibit radiographic progression of disease. New insights into the molecules involved in ankylosis (such as bone morphogenetic proteins and Wnts) have suggested that the classical paradigm linking inflammation and ankylosis can be challenged, and new concepts of disease onset and progression, with a focus on cell stress and damage, are rapidly evolving. In RA, inhibition of Wnt signaling and defective osteoblast function have been associated with lack of repair. As restoration of tissue integrity and homeostasis is the ultimate goal of therapy, these findings suggest new roads for therapeutic intervention. For patients with AS or RA, such strategies will be critically dependent on further research that defines individual risk factors and need for interventions.

Key Points

  • Ankylosing spondylitis (AS) is characterized by extensive cartilage and bone formation, which leads to ankylosis in the sacroiliac joints and the spine

  • Ankylosis and ongoing inflammation both contribute to reduced mobility and increased disability in patients with AS

  • Radiographic progression of disease in AS (characterized by ankylosis) varies greatly between patients

  • In rheumatoid arthritis (RA), suppression of osteoblast activity interferes with healing of erosions; why this inhibition persists even after clinical control of the disease has been achieved is unclear

  • The osteoimmunology research agenda in AS and RA is rapidly evolving, providing new insights into disease onset and the reason why symptoms manifest in the joint or spine

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Figure 1: Clinical outcome of chronic arthritis.
Figure 2: New bone formation in AS.
Figure 3: Damage and lack of repair in rheumatoid arthritis.

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  1. Division of Rheumatology, Laboratory for Skeletal Development and Joint Disorders, Katholieke Universiteit Leuven, Herestraat 49, Leuven, B3000, Belgium

    Rik Lories

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The author has acted as a consultant for Abbott, MSD and Pfizer, has been a member of speakers bureau for MSD and Pfizer, and received grant or research support from Abbott and Pfizer. Katholieke Universiteit Leuven, Belgium, holds a patent on behalf of the author related to the use of bone morphogenetic protein antagonists in spondyloarthritis.

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Lories, R. The balance of tissue repair and remodeling in chronic arthritis. Nat Rev Rheumatol 7, 700–707 (2011). https://doi.org/10.1038/nrrheum.2011.156

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