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A Systems View of Risk Factors for Knee Osteoarthritis Reveals Insights into the Pathogenesis of the Disease

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Abstract

Early detection of osteoarthritis (OA) remains a critical yet unsolved multifaceted problem. To address the multifaceted nature of OA a systems model was developed to consolidate a number of observations on the biological, mechanical and structural components of OA and identify features common to the primary risk factors for OA (aging, obesity and joint trauma) that are present prior to the development of clinical OA. This analysis supports a unified view of the pathogenesis of OA such that the risk for developing OA emerges when one of the components of the disease (e.g., mechanical) becomes abnormal, and it is the interaction with the other components (e.g., biological and/or structural) that influences the ultimate convergence to cartilage breakdown and progression to clinical OA. The model, applied in a stimulus-response format, demonstrated that a mechanical stimulus at baseline can enhance the sensitivity of a biomarker to predict cartilage thinning in a 5 year follow-up in patients with knee OA. The systems approach provides new insight into the pathogenesis of the disease and offers the basis for developing multidisciplinary studies to address early detection and treatment at a stage in the disease where disease modification has the greatest potential for a successful outcome.

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Authors and Affiliations

  1. Department of Mechanical Engineering, Stanford University, Durand 227, Stanford, CA, 94305, USA

    Thomas P. Andriacchi & Julien Favre

  2. Orthopaedic Surgery, Stanford University, Stanford, USA

    Thomas P. Andriacchi, J. C. Erhart-Hledik & Constance R. Chu

  3. Joint Preservation Center, Palo Alto VA, Palo Alto, CA, USA

    Thomas P. Andriacchi & Constance R. Chu

  4. Muskuloskeletal Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland

    Julien Favre

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  1. Thomas P. Andriacchi
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  2. Julien Favre
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  3. J. C. Erhart-Hledik
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  4. Constance R. Chu
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Correspondence to Thomas P. Andriacchi.

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Associate Editor Amit Gefen oversaw the review of this article.

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Andriacchi, T.P., Favre, J., Erhart-Hledik, J.C. et al. A Systems View of Risk Factors for Knee Osteoarthritis Reveals Insights into the Pathogenesis of the Disease. Ann Biomed Eng 43, 376–387 (2015). https://doi.org/10.1007/s10439-014-1117-2

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