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Osteoarthritis: Current Molecular Biomarkers and the Way Forward

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Abstract

The ultimate hope of researchers and patients is a pathway to development of treatments for osteoarthritis to modify the disease process in addition to the symptoms. However, development of disease modifying drugs requires objective endpoints such as measures of joint structure, joint tissue homeostasis and/or joint survival–measures such as provided by imaging biomarkers, molecular biomarkers and joint replacement frequency, respectively. Although biomarkers supporting investigational drug use and drug approval include surrogate endpoints that may not necessarily reflect or directly correlate with the clinical outcome of interest, a formal biomarker qualification process currently exists that is a rigorous three stage process that yields biomarker approvals (or denials) for specific contexts of use. From a cost perspective, biochemical biomarkers are the ‘ones to beat’; however, even well-validated biomarkers may not cross the translation gaps for eventual use in healthcare unless they offer an advantage in terms of cost per quality adjusted life year. This review summarizes the case FOR and AGAINST biomarkers in drug development and highlights the current data for a subset of biomarkers in the osteoarthritis research field informing on cartilage homeostasis, joint inflammation and altered subchondral bone remodeling.

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  1. Division of Rheumatology, Duke Molecular Physiology Institute, Duke University School of Medicine, 300 North Duke St, Box 104775, Durham, NC, 27701, USA

    Virginia Byers Kraus

  2. Rheumatology, Biomarkers and Research, Nordic Bioscience, Herlev, Denmark

    Morten A. Karsdal

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Both VBK and MAK drafted and critically revised the important intellectual content of this manuscript; both approved the final version for submission and both take responsibility for the accuracy of the article.

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Correspondence to Virginia Byers Kraus.

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Dr. Morten Karsdal is the Chief Executive Officer of Nordic Bioscience. Nordic Bioscience has pending patents related to several biomarkers described in this review (PIIBNP/PRO-C2, C1M and C4M). Dr. V Kraus has no conflicts to declare.

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Kraus, V.B., Karsdal, M.A. Osteoarthritis: Current Molecular Biomarkers and the Way Forward. Calcif Tissue Int 109, 329–338 (2021). https://doi.org/10.1007/s00223-020-00701-7

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