Biomarkers Consortium – Osteoarthritis Biomarkers Project

The Problem
In knee osteoarthritis clinical trials, the traditional measure used to predict a patient’s disease progression and response to treatment (i.e., radiographic measurement of narrowing joint space) has limited utility.
The Solution
The Osteoarthritis Biomarkers project identified novel knee osteoarthritis biomarkers with the greatest utility for predicting disease progression and treatment response in clinical trials.


The Biomarkers Consortium’s Osteoarthritis Biomarkers Project identified radiographic measures, MRI measures and biochemical markers of knee osteoarthritis (OA) that outperform the radiographic measurement of joint space narrowing (JSN) (the outmoded “gold standard” measure) in knee osteoarthritis (OA) patients. Specifically, this project discovered biomarkers that measure early progression of structural and symptomatic changes in the knee joint over time and predict treatment responses in OA.

The study was conducted by a team of leading OA scientists and clinicians led by David J.  Hunter, M.D., Ph.D., from the    University of Sydney in Australia and Virginia Byers Kraus, M.D., Ph.D., from Duke University. The project team designed a nested case-controlled cohort known as the FNIH Cohort within the larger Osteoarthritis Initiative (OAI) dataset. The FNIH cohort contains 194 patients with clinically meaningful progression of both radiographic JSN and symptoms over the course of 48 months and controls of 406 patients that did not meet these progression criteria. Using longitudinal x-ray, MRI, serum and urine data from the FNIH Cohort, Researchers selected biomarkers that can be used to measure significant changes in the structure of cartilage and bone of knee OA patients, better predicting which patients will progress with knee OA disease and the likelihood of treatment response. The use of these biomarkers in clinical trials will enable stratification and enrichment of patients who are at the highest risk for OA progression, thereby facilitating smaller, shorter trials of new OA treatments in more narrowly targeted populations. The best performing biomarkers found from this study are currently being validated in a second project: PROGRESS OA – Clinical Evaluation and Qualification of Osteoarthritis Biomarkers in order to be used in future clinical trials and regulatory decision-making.


Public-Sector Partners

  • National Institutes of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
  • National Institute on Aging (NIA)
  • U.S. Food and Drug Administration (FDA)

Private-Sector Partners

  • AbbVie Inc.*
  • Amgen, Inc.*
  • Arthritis Foundation*
  • Bioiberica, S.A.*
  • DePuy Mitek Inc.*
  • Flexion Therapeutics Inc.*
  • GlaxoSmithKline*
  • Merck KGaA*
  • Osteoarthritis Research Society International (OARSI)*
  • Rottapharm Madaus*
  • Sanofi*
  • Stryker Corporation*

Academic Partners

  • Brigham and Woman’s Hospital
  • Duke University
  • University of California-San Francisco
  • University of Sydney

*Provided financial or in-kind support for this program.

FNIH Contact


  • Identify prognostic biomarkers of OA disease progression.
  • Examine the relationship between putative efficacy of intervention markers (biochemical markers, imaging features on x-ray and MRI and their progression) and clinically relevant outcomes.
  • Develop a risk score using baseline values of several biomarkers including joint space narrowing (JSN), bone trabecular integrity/fractal signal analysis (BTI/FSA), knee alignment, quantitative and semi-q-MRI measures and biochemical biomarkers that would predict which patients would  progress rapidly to clinical OA.

Results & Accomplishments

Established Novel Biomarkers

The FNIH OA Biomarkers Project Team has identified multiple imaging and biochemical biomarkers of cartilage morphometry, collagen degradation and bone resorption (at baseline and with change over time) that function as predictors of OA progression and symptomatic pain.

Scientific Publications

This project led to 23 peer-reviewed scientific publications as well as various abstracts.

  • Association of quantitative measures of medial meniscal extrusion with structural and symptomatic knee osteoarthritis progression – Data from the OAI FNIH biomarker study. Sharma K, Eckstein F, Maschek S, Roth M, Hunter DJ, Wirth W. 2023 Jul;S1063-4584(23)00863-4 Read more
  • Worsening of Articular Tissue Damage as Defined by Semi-Quantitative MRI Is Associated With Concurrent Quantitative Cartilage Loss Over 24 Months. Roemer F, Maschek S, Wisser A, Guermazi A, Hunter D, Eckstein F, Wirth W. Cartilage. 2023 Mar;14(1):39-47. Read more
  • A “best-in-class” systemic biomarker predictor of clinically relevant knee osteoarthritis structural and pain progression. Zhou K, Li YJ, Soderblom EJ, Reed A, Jain V, Sun S, Moseley MA, Kraus VB. Sci Adv. 2023 Jan 25;9(4):eabq5095. Read more
  • Establishment of reference intervals for osteoarthritis-related soluble biomarkers: the FNIH/OARSI OA Biomarkers Consortium. Kraus VB, Hargrove DE, Hunter DJ, Renner JB, Jordan JM. Ann Rheum Dis. 2017 Jan;76(1):179-185. Read more
  • Multivariable modeling of biomarker data from the phase 1 Foundation for the NIH Osteoarthritis Biomarkers Consortium. Hunter, D.J., Deveza, L.A., Collins, J.E., Losina, E., Nevitt, M.C., Roemer, F.W., Guermazi, A., Bowes, M.A., Dam, E.B., Eckstein, F., Lynch, J.A., Katz, J.N., Kwoh, C.K., Hoffmann, S. and Kraus, V.B. (2021), Arthritis Care Res. Accepted Author Manuscript.  Read more
  • Association of knee OA structural phenotypes to risk for progression: a secondary analysis from the Foundation for National Institutes of Health Osteoarthritis Biomarkers study (FNIH). Roemer FW, Collins JE, Neogi T, Crema MD, Guermazi A; Osteoarthritis and Cartilage 2020 May. Read more
  • Predictive validity of radiographic trabecular bone texture in knee OA – The OARSI / FNIH OA biomarkers consortium. Kraus VB, Collins JE, Charles HC, Pieper CF, Whitley L, Losina E, Nevitt M, Hoffmann S, Roemer F, Guermazi A, Hunter DJ; OA Biomarkers Consortium. Arthritis Rheumatol. 2018 Jan;70(1):80-87. Read more
  • Predictive and concurrent validity of cartilage thickness change as a marker of knee osteoarthritis progression: data from the Osteoarthritis Initiative. Wirth W, Hunter DJ, Nevitt MC, Sharma L, Kwoh CK, Ladel C, Eckstein F. Osteoarthritis Cartilage. 2017 Dec;25(12):2063-2071. Read more
  • Semi-Quantitative Imaging Biomarkers of Knee Osteoarthritis Progression: Data from the FNIH OA Biomarkers Consortium. Collins JE, Losina E, Nevitt MC, Roemer FW, Guermazi A, Lynch JA, Katz JN, Kwoh CK, Kraus VB, Hunter DJ. Arthritis Rheumatol. 2016 Oct;68(10):2422-31. Read more
  • Predictive validity of biochemical biomarkers in knee osteoarthritis: data from the FNIH OA Biomarkers Consortium. Kraus VB, Collins JE, Hargrove D, Losina E, Nevitt M, Katz JN, Wang S, Sandell LJ, Hoffmann SC, Hunter DJ, FNIH OA Biomarkers Consortium. Am J Phys Med Rehabil. 2016 Dec;95(12):931-938. Read more
  • Biomarkers for osteoarthritis: current position and steps towards further validation. Hunter DJ, Nevitt M, Losina E, Kraus V. Best Pract Res Clin Rheumatol. 2014 Feb;28(1):6171.  Read more

Data Access

Upon request, OAI Database users may obtain biospecimens and images used in the study. IMPORTANT: Use of the data intended for publication should follow OAI publication guidelines and all project-specific guidelines and instructions noted on the OA Biomarkers Consortium FNIH Project page(s).


This project has been featured in various media outlets, including the following:

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