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Associations between serum levels of inflammatory markers and change in knee pain over 5 years in older adults: a prospective cohort study
  1. Oliver P Stannus1,
  2. Graeme Jones1,
  3. Leigh Blizzard1,
  4. Flavia M Cicuttini2,
  5. Changhai Ding1,2
  1. 1Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia
  2. 2Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
  1. Correspondence to Associate Professor Changhai Ding, Menzies Research Institute, Private Bag 23, Hobart, Tasmania 7000, Australia; changhai.ding{at}


Objective To determine the association between inflammatory markers and change in knee pain over 5 years.

Methods A total of 149 randomly selected subjects (mean 63 years, range 52–78; 46% female) was studied. Serum levels of high sensitivity C-reactive protein (hs-CRP), tumour necrosis factor alpha (TNF–α) and interleukin (IL)-6 were measured at baseline and 2.7 years later. Knee pain was recorded using the Western Ontario and McMasters osteoarthritis index questionnaire at baseline and 5 years later. Knee radiographic osteoarthritis of both knees was assessed at baseline, and knee bone marrow lesions, joint effusion and cartilage defects were determined using T1 or T2-weighted fat saturated MRI.

Results After adjustment for confounding variables, baseline hs-CRP was positively associated with change in total knee pain (β=0.33 per mg/l, p=0.032), as well as change in the pain at night in bed (β=0.12 per ml/pg, p=0.010) and while sitting/lying (β=0.12 per ml/pg, p=0.002). Change in hs-CRP was also associated with change in knee pain at night and when sitting/lying (both p<0.05). Baseline TNFα and IL-6 were associated with change in pain while standing (β=0.06 per ml/pg, p=0.033; β=0.16 per ml/pg, p=0.035, respectively), and change in TNFα was positively associated with change in total knee pain (β=0.66 ml/pg, p=0.020) and change in pain while standing (β=0.26 ml/pg, p=0.002). Adjustment for radiographic osteoarthritis or MRI-detected structural abnormalities led to no or minor attenuation of these associations.

Conclusion Systemic inflammation is an independent predictor of worsening knee pain over 5 years.

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  • Funding This study received funding from the National Health and Medical Research Council of Australia. CD is a recipient of an ARC future fellowship, and GJ is a recipient of a NHMRC practitioner fellowship.

  • Ethics approval The study was approved by the Southern Tasmanian Health and Medical Human Research Ethics Committee.

  • Patient consent Obtained.

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

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