Biomarkers Consortium - Osteoarthritis Project

This $3.4 million study determined which biomarkers have greater prognostic ability to measure early progression of structural and symptomatic changes in the joint over time and which are likely to predict treatment response better than the radiographic measurement of narrowing of joint space in knee osteoarthritis (OA) patients—the existing but outmoded “gold standard” biomarker of knee OA. Using longitudinal MRI, serum and urine data from nearly 5,000 patients with knee OA and controls, researchers were able to narrow thousands of biomarkers down to a select few that measure significant changes in the structure of cartilage and bone of knee OA patients and the pain they experience. They will enable stratification and clinical trial enrichment of those patients at the highest risk for OA progression, thereby facilitating smaller, shorter trials of new OA treatments. These new biomarkers are candidates for follow-on studies for evaluation and use in regulatory decision-making.

Goals

  • To identify the most responsive biomarkers of OA progression.
  • To 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.
  • To develop a risk score based on 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 determine those that progress rapidly to clinical OA.

Results & Accomplishments

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) as predictors of OA progression and symptomatic pain.

Scientific Publications

  2018

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. doi: 10.1002/art.40348

 

Is synovitis detected on non-contrast-enhanced magnetic resonance imaging associated with serum biomarkers and clinical signs of effusion? Data from the Osteoarthritis Initiative. Deveza LA, Kraus VB, Collins JE, Guermazi A, Roemer FW, Nevitt MC, Hunter DJ. Scand J Rheumatol. 2018 May;47(3):235-242. doi: 10.1080/03009742.2017.1340511.

 

Superolateral Hoffa's fat pad (SHFP) oedema and patellar cartilage volume loss: quantitative analysis using longitudinal data from the Foundation for the National Institute of Health (FNIH) Osteoarthritis Biomarkers Consortium. Haj-Mirzaian A, Guermazi 2, Hafezi-Nejad N, Sereni C, Hakky M, Hunter DJ, Zikria B, Roemer FW Demehri S. Eur Radiol. 2018 Apr 12. doi: 10.1007/s00330-018-5334-1.

 

Is synovitis detected on non-contrast-enhanced magnetic resonance imaging associated with serum biomarkers and clinical signs of effusion? Data from the Osteoarthritis Initiative. LA Deveza, VB Kraus, JE Collins, A Guermazi, FW Roemer, MC Nevitt, DJ Hunter (2018) Scandinavian Journal of Rheumatology, 47:3, 235-242, DOI:10.1080/03009742.2017.1340511

 

Imaging of osteoarthritis—recent research developments and future perspective. Daichi Hayashi, MD, PhD, Frank W Roemer, MD and Ali Guermazi, MD, PhD. Br J Radiol. 2018 May; 91(1085):20170349. doi: 10.1259/bjr.20170349.  

 

The relationship between two different measures of osteoarthritis bone pathology, bone marrow lesions and 3D bone shape: data from the Osteoarthritis Initiative. Dube B, Bowes MA, Hensor EMA, Barr A, Kingsbury SR, Conaghan PG. Osteoarthritis and Cartilage (2018), doi: 10.1016/j.joca.2018.06.011.

 

Quantitative measurement of cartilage volume is possible using two-dimensional magnetic resonance imaging data sets. Schaefer LF, Nikac V, Lynch JA, Duryea J. Osteoarthritis Cartilage. 2018 Jul;26(7):920-923. doi: 10.1016/j.joca.2018.04.005 

  2017

Association Between Biochemical Markers of Bone Turnover and Bone Changes on Imaging: Data From the Osteoarthritis Initiative. Leticia A. Deveza, Virginia B. Kraus, Jamie E. Collins, Ali Guermazi, Frank W. Roemer, Michael Bowes, Michael C. Nevitt, Christoph Ladel, and David J. Hunter. Arthritis Care Res (Hoboken). 2017 Aug;69(8):1179-1191. doi: 10.1002/acr.23121

 

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. doi: 10.1016/j.joca.2017.08.005

 

Quantitative measurement of medial femoral knee cartilage volume – analysis of the OA Biomarkers Consortium FNIH Study cohort. Schaefer LF, Sury M, Yin M, Jamieson S, Donnell I, Smith SE, Lynch JA, Nevitt MC, Duryea J. Osteoarthritis Cartilage. 2017 Jul;25(7):1107-1113. doi: 10.1016/j.joca.2017.01.010.

 

Between-group differences in infra-patellar fat pad size and signal in symptomatic and radiographic progression of knee osteoarthritis vs non-progressive controls and healthy knees - data from the FNIH Biomarkers Consortium Study and the Osteoarthritis Initiative. Ruhdorfer A, Haniel F, Petersohn T, Dörrenberg J, Wirth W, Dannhauer T, Hunter DJ, Eckstein F. Osteoarthritis Cartilage. 2017 Jul;25(7):1114-1121. doi: 10.1016/j.joca.2017.02.789.

 

  2016

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. doi: 10.1002/art.39731

 

Longitudinal validation of periarticular bone area and 3D shape as biomarkers for knee OA progression? Data from the FNIH OA Biomarkers Consortium. Hunter D, Nevitt M, Lynch J, Kraus VB, Katz JN, Collins JE, Bowes M, Guermazi A, Roemer FW, Losina E; FNIH OA Biomarkers Consortium. Ann Rheum Dis. 2016 Sep;75(9):160714.

 

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. 2016 Jun 24. pii: annrheumdis2016209253. doi: 10.1136/annrheumdis2016209253.

 

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.

 

Prediction of medial tibiofemoral compartment joint space loss progression using volumetric cartilage measurements: Data from the FNIH OA biomarkers consortium. Hafezi-Nejad N, Guermazi A, Roemer FW, Hunter DJ, Dam EB, Zikria B, Kwoh CK, Demehri S. Eur Radiol. 2016 May 24. doi:10.1007/s00330-016-4393-4

 

Predictive Capacity of Thigh Muscle Strength in Symptomatic and/or Radiographic Knee Osteoarthritis Progression: Data from the Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium. Culvenor AG, Wirth W, Roth M, Hunter DJ, Eckstein F. Am J Phys Med Rehabil. 2016 May 12. [Epub ahead of print] doi: 10.1097/PHM.0000000000000534

 

Semi-quantitative MRI biomarkers of knee osteoarthritis progression in the FNIH biomarkers consortium cohort − Methodologic aspects and definition of change. Roemer FW, Guermazi A, Collins JE, Losina E, Nevitt MC, Lynch JA, Katz JN. BMC Musculoskelet Disord. 2016 Nov 10;17(1):466.

 

  2015

Brief Report: Cartilage Thickness Change as an Imaging Biomarker of Knee Osteoarthritis Progression: Data From the Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium. Eckstein F, Collins JE, Nevitt MC, Lynch JA, Kraus VB, Katz JN, Losina E, Wirth W, Guermazi A, Roemer FW, Hunter DJ; FNIH OA Biomarkers Consortium. Arthritis Rheumatol. 2015 Dec;67(12):31849. doi: 10.1002/art.39324

 

  2014

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 doi:10.1016/j.berh.2014.01.007

 

Selected Abstracts

Preliminary Assessment of Predictive Validity of Cartilage Thickness MRI Biomarkers in Knee OA the FNIH OA Biomarkers Consortium. Hunter DJ, Collins J, Nevitt M, Lynch J, Kraus V, Katz J, Losina E, Roemer F, Guermazi A, Wirth W, Eckstein F. Arthritis and Rheumatism 2014;66:S87.

Preliminary Assessment of Predictive Validity of Semi-Quantitative MRI Biomarkers in Knee OA the FNIH OA Biomarkers Consortium. Hunter DJ, Nevitt M, Collins J, Roemer FW, Lynch J, Kraus V, Katz JN, Losina E, Jordan JM, Guermazi A. Osteoarthr Cartilage 2014;22:S238S.

Associations Among a Spectrum of Knee Osteoarthritis Features on MRI Inform about Potential Pathogenic Mechanisms, Data from the OAI/FNIH Biomarkers Consortium. W.E. Van Spil, L.A. Deveza, D.J. Hunter

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).

Media

BioWorld Today Highlights FNIH OA Biomarkers Project

FNIH Press Release, October 21, 2015: New Study Advances Biomarkers that Predict Structural Change and Pain Progression in Knee Osteoarthritis

Osteoarthritis Research Society International World Congress Update, April 30th, 2015

Slides from the Pre-Congress Workshop

Partners

AbbVie Inc.
Amgen, Inc.
Arthritis Foundation
Bioiberica, S.A.
Brigham and Woman’s Hospital
DePuy Mitek Inc.
Duke University
Flexion Therapeutics Inc.
Food and Drug Administration
GlaxoSmithKline
Merck KGaA
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Institute on Aging (NIA)
Osteoarthritis Research Society International (OARSI)
Rottapharm Madaus
Sanofi
Stryker Corporation
University of California-San Francisco
University of Sydney

Contact

Steve Hoffmann, Director, Inflammation and Immunity, shoffmann@fnih.org