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Value of biomarkers in osteoarthritis: current status and perspectives

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Lotz, M, Martel-Pelletier, J, Christiansen, C, Brandi, M-L, Bruyère, O, Chapurlat, R, Collette, J, Cooper, C +13 more·2013·Annals of the Rheumatic Diseases
DOI 10.1136/annrheumdis-2013-203726PMC PMC3812859
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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.

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  • International consortia like the FNIH and OARSI are developing standardized protocols, reference materials, and quality management systems to ensure measurement reliability and facilitate clinical implementation.

    “with international consortia like the FNIH and OARSI developing standardized protocols, reference materials, and quality management systems to ensure measurement reliability and facilitate clinical implementation [162].”

    From Biomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease (2025) · cites this paper as [162]

    The Discussion (page unavailable) describes an ongoing OARSI/Foundation for NIH comparison of biomarkers and identifies standardisation and calibration as future research needs to address measurement errors. It does not say those organisations are developing standardized protocols, reference materials, or quality management systems, nor that such systems are facilitating clinical implementation. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Biomarker standardization addresses technical variability across preanalytical, analytical, and post-analytical phases.

    “Biomarker standardization addresses technical variability across preanalytical, analytical, and post-analytical phases”

    From Biomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease (2025) · cites this paper as [162]

    The Discussion (page unavailable) identifies errors related to sampling and assay characteristics and recommends standardisation, calibration, and improved data collection to address them. It does not describe variability across all three named phases or specifically address the post-analytical phase; it presents standardisation as a needed improvement, not an achieved solution. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

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Authors
Lotz, M., Martel-Pelletier, J., Christiansen, C., Brandi, M.-L., Bruyère, O., Chapurlat, R., Collette, J., Cooper, C., Giacovelli, G., Kanis, J. A., Karsdal, M. A., Kraus, V, Lems, W. F., Meulenbelt, I., Pelletier, J.-P., Raynauld, J.-P., Reiter-Niesert, S., Rizzoli, R., Sandell, L. J., Van Spil, W. E., & Reginster, J.-Y.
Affiliations
  • Scripps Research Institute (US)
  • Nordic Bioscience (Denmark) (DK)
  • University of Florence (IT)
  • University of Liège (BE)
  • Inserm (FR)
  • University of Oxford (GB)
  • Duke University (US)
  • Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
  • Leiden University Medical Center (NL)
  • Université de Montréal (CA)
  • Federal Institute for Drugs and Medical Devices (DE)
  • University of Geneva (CH)
  • Washington University in St. Louis (US)
Corresponding author
Lotz, M
ORCID
Venue
Annals of the Rheumatic Diseases
Publisher
Elsevier BV
Published
2013-11
Volume
72
Issue
11
Pages
1756-1763
ISSN
0003-4967 (ISSN-L)
DOI
10.1136/annrheumdis-2013-203726
PMC
PMC3812859
OpenAlex
W2128468094
Cited by
328
References
3
Citations by year
2026: 9 · 2025: 21 · 2024: 18 · 2023: 27 · 2022: 18 · 2021: 20 · 2020: 27 · 2019: 16 · 2018: 31 · 2017: 42 · 2016: 37 · 2015: 44 · 2014: 17 · 2013: 1
FWCI
27.00
Type
journal article
Language
en
Update notices
erratum (2017-09-01)
Open access
Licence
Locations
  • Annals of the Rheumatic Diseases (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
  • Research Bank (Australian Catholic University) (submittedVersion, cc-by-nc)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Leiden Repository (Leiden University) (submittedVersion)
  • ePrints Soton (University of Southampton) (submittedVersion)
  • Florence Research (University of Florence) (submittedVersion)
  • Open Repository and Bibliography (University of Liège) (submittedVersion)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders
  • National Institute for Health and Care Research (NF-SI-0508-10082)
  • Medical Research Council (MC_UU_12011/1)
Topics
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
  • Health Sciences › Medicine › Pharmacology › Musculoskeletal pain and rehabilitation
Keywords
osteoarthritis, biomarkers, collagen metabolism, non-collagenous proteins, synovitis, fibrosis, cartilage oligomeric matrix protein, disease progression, prognosis, surrogate endpoints, biomarker panel, imaging biomarkers, drug development
MeSH terms
Cartilage, Articular, Humans, Osteoarthritis, Synovial Membrane, Biomarkers, Disease Progression

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