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Value of biomarkers in osteoarthritis: current status and perspectives
  1. M Lotz1,
  2. J Martel-Pelletier2,
  3. C Christiansen3,
  4. M-L Brandi4,
  5. O Bruyère5,
  6. R Chapurlat6,
  7. J Collette7,
  8. C Cooper8,9,
  9. G Giacovelli10,
  10. J A Kanis11,
  11. M A Karsdal3,
  12. V Kraus12,
  13. W F Lems13,
  14. I Meulenbelt14,
  15. J-P Pelletier2,
  16. J-P Raynauld2,
  17. S Reiter-Niesert15,
  18. R Rizzoli16,
  19. L J Sandell17,
  20. W E Van Spil18,
  21. J-Y Reginster19
  1. 1Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA
  2. 2Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Montreal, Quebec, Canada
  3. 3Nordic Bioscience A/S, Herlev, Denmark
  4. 4Metabolic Bone Unit, Department of Internal Medicine, University of Florence, Florence, Italy
  5. 5Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
  6. 6INSERM UMR 1033 and Université de Lyon, Service de Rhumatologie et Pathologie Osseuse, Hôpital Edouard Herriot, Lyon, France
  7. 7Department of Clinical Chemistry, Bone and Cartilage Markers Laboratory, CHU, University of Liège, Liège, Belgium
  8. 8MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK
  9. 9NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK
  10. 10Clinical Research Unit, Rottapharm Madaus Group, Monza, Italy
  11. 11WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK
  12. 12Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
  13. 13Department of Rheumatology, VU University Medical Centre, Amsterdam, The Netherlands
  14. 14Leiden University Medical Centre, Section of Molecular Epidemiology, Leiden, The Netherlands
  15. 15Federal Institute for Drugs and Medical Devices (BfArM), Bonn, Germany
  16. 16Division of Bone Diseases, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland
  17. 17Department of Cell Biology and Physiology, Washington University, St Louis, Missouri, USA
  18. 18Department of Rheumatology and Clinical immunology, University Medical Center Utrecht, Utrecht, The Netherlands
  19. 19Bone and Cartilage Metabolism Research Unit and Department of Public Health Sciences, CHU Centre-Ville, Policliniques L. Brull, University of Liège, Liège, Belgium
  1. Correspondence to Professor M Lotz, Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; mlotz{at}scripps.edu

Abstract

Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis convened to discuss the value of biochemical markers of matrix metabolism in drug development in osteoarthritis. The best candidates are generally molecules or molecular fragments present in cartilage, bone or synovium and may be specific to one type of joint tissue or common to them all. Many currently investigated biomarkers are associated with collagen metabolism in cartilage or bone, or aggrecan metabolism in cartilage. Other biomarkers are related to non-collagenous proteins, inflammation and/or fibrosis. Biomarkers in osteoarthritis can be categorised using the burden of disease, investigative, prognostic, efficacy of intervention, diagnostic and safety classification. There are a number of promising candidates, notably urinary C-terminal telopeptide of collagen type II and serum cartilage oligomeric protein, although none is sufficiently discriminating to differentiate between individual patients and controls (diagnostic) or between patients with different disease severities (burden of disease), predict prognosis in individuals with or without osteoarthritis (prognostic) or perform so consistently that it could function as a surrogate outcome in clinical trials (efficacy of intervention). Future avenues for research include exploration of underlying mechanisms of disease and development of new biomarkers; technological development; the ‘omics’ (genomics, metabolomics, proteomics and lipidomics); design of aggregate scores combining a panel of biomarkers and/or imaging markers into single diagnostic algorithms; and investigation into the relationship between biomarkers and prognosis.

  • Osteoarthritis
  • Outcomes research
  • Inflammation

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