Article Text

Download PDFPDF
Extended report
Longitudinal validation of periarticular bone area and 3D shape as biomarkers for knee OA progression? Data from the FNIH OA Biomarkers Consortium
  1. David Hunter1,
  2. Michael Nevitt2,
  3. John Lynch2,
  4. Virginia Byers Kraus3,
  5. Jeffrey N Katz4,
  6. Jamie E Collins4,
  7. Mike Bowes5,
  8. Ali Guermazi6,
  9. Frank W Roemer6,7,
  10. Elena Losina4
  11. for the FNIH OA Biomarkers Consortium
  1. 1Rheumatology Department, Royal North Shore Hospital and Institute of Bone and Joint Research, Kolling Institute, University of Sydney, Sydney, New South Wales, Australia
  2. 2Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA
  3. 3Duke Molecular Physiology Institute and Division of Rheumatology, Duke University School of Medicine, Durham, North Carolina, USA
  4. 4Brigham and Women's Hospital, Boston, Massachusetts, USA
  5. 5Imorphics, Manchester, UK
  6. 6Department of Radiology, Boston University School of Medicine, Quantitative Imaging Center, Boston, Massachusetts, USA
  7. 7Department of Radiology, University of Erlangen-Nuremberg, Erlangen, Germany
  1. Correspondence to Dr Hunter at Rheumatology Department, Royal North Shore Hospital and Institute of Bone and Joint Research, Kolling Institute, University of Sydney, Sydney, NSW 2065, Australia; David.Hunter{at}


Objective To perform a longitudinal validation study of imaging bone biomarkers of knee osteoarthritis (OA) progression.

Methods We undertook a nested case–control study within the Osteoarthritis Initiative in knees (one knee per subject) with a Kellgren and Lawrence grade of 1–3. Cases were defined as knees having the combination of medial tibiofemoral radiographic progression and pain progression at the 24-month, 36-month or 48-month follow-up compared with baseline. Controls (n=406) were eligible knees that did not meet both endpoint criteria and included 200 with neither radiographic nor pain progression, 103 with radiographic progression only and 103 with pain progression only. Bone surfaces in medial and lateral femur, tibia and patella compartments were segmented from MR images using active appearance models. Independent variables of primary interest included change from baseline to 24 months in (1) total area of bone and (2) position on three-dimensional (3D) bone shape vectors that discriminate OA versus non-OA shapes. We assessed the association of bone markers changes over 24 months with progression using logistic regression.

Results 24-month changes in bone area and shape in all compartments were greater in cases than controls, with ORs of being a case per 1 SD increase in bone area ranging from 1.28 to 1.71 across compartments, and per 1 SD greater change in 3D shape vectors ranging from 1.22 to 1.64. Bone markers were associated most strongly with radiographic progression and only weakly with pain progression.

Conclusions In knees with mild-to-moderate radiographic OA, changes in bone area and shape over 24 months are associated with the combination of radiographic and pain progression over 48 months. This finding of association with longer term clinical outcome underscores their potential for being an efficacy of intervention biomarker in clinical trials.

  • Osteoarthritis
  • Knee Osteoarthritis
  • Magnetic Resonance Imaging

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.