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Does cartilage loss cause pain in osteoarthritis and if so, how much?
  1. Kathryn Bacon1,
  2. Michael P LaValley2,
  3. S Reza Jafarzadeh3,
  4. David Felson3,4
  1. 1 Rheumatology, Boston University, Boston, Massachusetts, USA
  2. 2 Biostatistics, School of Public Health, Boston, Massachusetts, USA
  3. 3 Section of Rheumatology, Boston University School of Medicine, Boston, Massachusetts, USA
  4. 4 Centre for Epidemiology Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester and NIHR Manchester Musculoskeletal Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
  1. Correspondence to Professor David Felson, boston university, Boston, Massachusetts, USA; dfelson{at}


Objectives Although treatment development in osteoarthritis (OA) focuses on chondroprotection, it is unclear how much preventing cartilage loss reduces joint pain. It is also unclear how nociceptive tissues may be involved.

Methods Using data from the Osteoarthritis Initiative, we quantified the relation between cartilage loss and worsening knee pain after adjusting for bone marrow lesions (BMLs) and synovitis, and examined how much these factors mediated this association. 600 knee MRIs were scored at baseline, 12 months and 24 months for quantitative and semiquantitative measures of OA structural features. We focused on change in medial cartilage thickness using an amount similar to that seen in recent trials. Linear models calculated mean change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score with cartilage loss, adjusted for baseline BMLs, synovitis and covariates. Mediation analysis tested whether change in synovitis or BMLs mediated the cartilage loss–pain association. We carried out a subanalysis for knees with non-zero baseline WOMAC pain scores and another for non-valgus knees.

Results Cartilage thickness loss was significantly associated with a small degree of worsening in pain over 24 months. For example, a loss of 0.1 mm of cartilage thickness over 2 years was associated with a 0.32 increase in WOMAC pain (scale 0–20). The association of cartilage thickness loss with pain was mediated by synovitis change but not by BML change. Subanalysis results were similar.

Conclusions Cartilage thickness loss is associated with only a small amount of worsening knee pain, an association mediated in part by worsening synovitis. Demonstrating that chondroprotection reduces knee pain will be extremely challenging and is perhaps unachievable.

  • osteoarthritis, knee
  • synovitis
  • MRI
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  • Handling editor Josef S Smolen

  • Contributors KB: Conception and design, drafting of article, performing analysis. MPL and SRJ: editing article, overseeing analysis. DF: Conception and design, drafting of article. All authors: final approval of manuscript.

  • Funding This study was funded by National Institutes of Health; grant number (P30 AR072571).

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available in a public, open access repository. The data used for analyses in this paper are publicly available at

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