title: Association of urinary biomarker COLL2-1NO₂ with incident clinical and radiographic knee OA in overweight and obese women.
abstract: OBJECTIVE
  To investigate the association between urinary biomarker Coll2-1NO2 (uColl2-1NO2) and incident knee OA after 2.5 years follow-up in middle-aged overweight and obese women at high risk for knee osteoarthritis (OA).
  
  
  METHODS
  Data were used from PROOF, a randomized controlled trial with 2.5 years follow-up evaluating the preventive effects of a diet and exercise program and oral glucosamine sulphate (double blind and placebo controlled), on development of incident knee OA in women with body mass index ≥ 27 kg/m(2) without signs of knee OA at baseline. Baseline and 2.5 years uColl2-1NO2 concentrations were assessed with enzyme-linked immunosorbent assay (ELISA). Primary outcome measure was incidence of knee OA in one or both knees, defined as incidence of either Kellgren & Lawrence grade ≥2, joint space narrowing of ≥1.0 mm or knee OA according to the combined clinical and radiographic ACR-criteria. We used binary logistic regression for the association analyses.
  
  
  RESULTS
  254 women were available for analyses. At 2.5 years follow-up, incident knee OA was present in 72 of 254 women (28.3%). An inversed association was found between baseline uColl2-1NO2 and incident knee OA at 2.5 years (OR 0.74, 95% CI 0.55-0.99). The concentration at 2.5 years and the change in concentration over 2.5 years did not show significant associations with the outcome.
  
  
  CONCLUSIONS
  In overweight and obese middle-aged women, not higher but lower baseline uColl2-1NO2 concentration was significantly associated with an increased risk for incident knee OA. This interesting but counterintuitive outcome makes further validation of this biomarker warranted.
authors.affiliation: Department of General Practice, Erasmus MC, University Medical Center Rotterdam, The Netherlands. Electronic address: m.landsmeer@erasmusmc.nl.
authors.forename: M L A
authors.initials: ML
authors.lastname: Landsmeer
authors.affiliation: Department of General Practice, Erasmus MC, University Medical Center Rotterdam, The Netherlands. Electronic address: j.runhaar@erasmusmc.nl.
authors.forename: J
authors.initials: J
authors.lastname: Runhaar
authors.affiliation: Bone and Cartilage Research Unit, University of Liège, Sart Tilman, 4000 Liège, Belgium; Physical Therapy and Rehabilitation Department, Princess Paola Hospital, Marche-en-Famenne, Belgium. Electronic address: yhenrotin@ulg.ac.be.
authors.forename: Y E
authors.initials: YE
authors.lastname: Henrotin
authors.affiliation: Department of General Practice, Erasmus MC, University Medical Center Rotterdam, The Netherlands. Electronic address: m.vanmiddelkoop@erasmusmc.nl.
authors.forename: M
authors.initials: M
authors.lastname: Middelkoop van
authors.affiliation: Department of Radiology, Erasmus MC, University Medical Center Rotterdam, The Netherlands. Electronic address: e.oei@erasmusmc.nl.
authors.forename: E H G
authors.initials: EH
authors.lastname: Oei
authors.affiliation: Department of Radiology, Maasstad Hospital, Rotterdam, The Netherlands. Electronic address: vroegindeweijd@maasstadziekenhuis.nl.
authors.forename: D
authors.initials: D
authors.lastname: Vroegindeweij
authors.affiliation: Department of Orthopaedics, Erasmus MC, University Medical Center Rotterdam, The Netherlands. Electronic address: m.reijman@erasmusmc.nl.
authors.forename: M
authors.initials: M
authors.lastname: Reijman
authors.affiliation: Department of Orthopaedics, Erasmus MC, University Medical Center Rotterdam, The Netherlands. Electronic address: g.vanosch@erasmusmc.nl.
authors.forename: G J V M
authors.initials: GJ
authors.lastname: van Osch
authors.affiliation: Department of General Practice, Erasmus MC, University Medical Center Rotterdam, The Netherlands. Electronic address: b.koes@erasmusmc.nl.
authors.forename: B W
authors.initials: BW
authors.lastname: Koes
authors.affiliation: Department of General Practice, Erasmus MC, University Medical Center Rotterdam, The Netherlands. Electronic address: p.bindels@erasmusmc.nl.
authors.forename: P J E
authors.initials: PJ
authors.lastname: Bindels
authors.affiliation: Department of General Practice, Erasmus MC, University Medical Center Rotterdam, The Netherlands; Department of Orthopaedics, Erasmus MC, University Medical Center Rotterdam, The Netherlands. Electronic address: s.bierma-zeinstra@erasmusmc.nl.
authors.forename: S M A
authors.initials: SM
authors.lastname: Bierma-Zeinstra
mesh_terms: D015415:Biomarkers / Q000652:urine; D024043:Collagen Type II / Q000652:urine*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D009765:Obesity / Q000453:epidemiology*; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000652:urine*; D050177:Overweight / Q000453:epidemiology*; D010446:Peptide Fragments / Q000652:urine*; D011859:Radiography
chemical_list: D015415:Biomarkers; D024043:Collagen Type II; D010446:Peptide Fragments; C510281:collagen type II (108-116), (NO2)Tyr(111)-
keywords: Biomarker; Coll2-1NO(2); Knee; Osteoarthritis