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Prospects for disease modification in osteoarthritis

Nature Clinical Practice Rheumatology volume 2, pages 304–312 (2006)Cite this article

Abstract

Osteoarthritis (OA) can be a progressive, disabling disease, leading to diminished quality of life, and, for over 500,000 individuals annually in the US, total joint replacement. The etiology of OA will vary among individuals, with potential roles for systemic factors (such as genetics and obesity) as well as for local biomechanical factors (such as muscle weakness, joint laxity and traumatic injury). Joint deterioration occurs over extended periods of time, and the diverse molecular mechanisms that mediate pathogenic events of early, mid and late disease are not yet fully understood. The success of biologic therapies in the treatment of rheumatoid arthritis has demonstrated that the blockade of a single dominant cytokine or regulatory molecule can prevent cartilage destruction in a complex disease, and has raised expectations that mechanism-based treatments could also be developed for patients with OA. In this review, we will address the biological mechanisms that mediate structural damage in OA and examine current targets that are candidates for disease modification. The challenges to drug development and the obstacles to disease modification strategies will also be addressed.

Key Points

  • Osteoarthritis affects the three major components (bone, synovium, and cartilage) of diarthrodial joints, which produce cytokines, growth factors, proteases and other mediators that have been implicated in disease progression

  • Progressive destruction of articular cartilage is characterized by the dysregulation of anabolic and catabolic metabolic pathways; determination of these pathophysiologic processes could lead to the identification of specific targets for disease-modifying drugs

  • Currently available agents (such as glucosamine, hyaluronans, diacerein, bisphosphonates and doxycycline) have been reported to affect disease progression in osteoarthritis; however, the studies are inconclusive, and none of these agents have met regulatory criteria for structure modification

  • Inhibitors of interleukin-1, nitric-oxide synthase, bone resorption and matrix metalloproteinases are in clinical development as potential disease-modifying drugs

  • DMOAD development should be facilitated by improved imaging technology, as well as by the validation of biochemical markers of disease progression and activity

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Figure 1: Schematic representation of key pathological events and potential targets for disease modification in osteoarthritis.

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Author information

Authors and Affiliations

  1. Chairman of Rheumatology at the New York University Hospital for Joint Diseases, New York, NY, USA

    Steven B Abramson

  2. Assistant Professor of Medicine and Director of the Rheumatology Research Laboratory,

    Mukundan Attur & Yusuf Yazici

  3. Assistant Professor of Medicine and Co-Director of the Seligman Center for Advanced Therapeutics,

    Mukundan Attur & Yusuf Yazici

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  1. Steven B Abramson
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  2. Mukundan Attur
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  3. Yusuf Yazici
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Corresponding author

Correspondence to Yusuf Yazici.

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Competing interests

SB Abramson: consultant to Amgen and Abbott; Y Yusuf: investigator on clinical trials sponsored by Amgen, Abbott, Roche, and Bristol Myers Squibb.

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Abramson, S., Attur, M. & Yazici, Y. Prospects for disease modification in osteoarthritis. Nat Rev Rheumatol 2, 304–312 (2006). https://doi.org/10.1038/ncprheum0193

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