title: Associations between serum levels of inflammatory markers and change in knee pain over 5 years in older adults: a prospective cohort study.
abstract: 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.
  
  
  CONCLUSIONS
  Systemic inflammation is an independent predictor of worsening knee pain over 5 years.
authors.affiliation: Menzies Research Institute, Private Bag 23, Hobart, Tasmania 7000, Australia.
authors.forename: Oliver P
authors.initials: OP
authors.lastname: Stannus
authors.forename: Graeme
authors.initials: G
authors.lastname: Jones
authors.forename: Leigh
authors.initials: L
authors.lastname: Blizzard
authors.forename: Flavia M
authors.initials: FM
authors.lastname: Cicuttini
authors.forename: Changhai
authors.initials: C
authors.lastname: Ding
mesh_terms: D017677:Age Distribution; D000368:Aged; D018771:Arthralgia / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D002358:Cartilage, Articular / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000473:pathology; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011859:Radiography; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein