title: Association between concentrations of urinary type II collagen neoepitope (uTIINE) and joint space narrowing in patients with knee osteoarthritis.
abstract: OBJECTIVE
  To examine whether urine concentrations of type II collagen neoepitope (uTIINE) distinguish subjects with progressive radiographic and/or symptomatic knee osteoarthritis (OA) from those with stable disease.
  
  
  METHODS
  Subjects were 120 obese middle-aged women with unilateral knee OA who participated in a 30-month randomized-controlled trial of structure modification with doxycycline, in which a standardized semiflexed anteroposterior view of the knee was obtained at baseline, 16 months and 30 months. Subjects were selected from a larger sample to permit a priori comparisons between 60 OA progressors and 60 nonprogressors, as defined by joint space narrowing (JSN) in the medial tibiofemoral compartment. Each group contained 30 subjects who exhibited clinically significant increases in knee pain over 30 months and 30 who did not. Urine samples were obtained every 6 months for determination of the creatinine (Cr)-adjusted uTIINE concentration.
  
  
  RESULTS
  Baseline uTIINE levels were unrelated to JSN in the placebo group. However, among subjects in the active treatment group, a 1-standard deviation increment in baseline uTIINE (68 ng/mM Cr) was associated with a marginally significant, two-fold increase in the odds of progression of JSN (odds ratio 2.04, 95% confidence interval 0.98-4.28). The within-subject mean of uTIINE values at baseline, 6 months and 12 months was associated with concurrent JSN measured at 16 months (0.10mm of JSN per 69 ng/mM Cr, P=0.008). Similar results were seen in the interval between months 16 and 30 and in analyses using the maximum of intercurrent uTIINE levels.
  
  
  CONCLUSIONS
  Baseline uTIINE was not a consistent predictor of JSN in subjects with knee OA. However, serial measurements of uTIINE reflect concurrent JSN.
authors.affiliation: Pfizer Global Research and Development, Ann Arbor, MI, USA; Pfizer Global Research and Development, St. Louis, MO, USA.
authors.forename: M-P
authors.initials: MP
authors.lastname: Hellio Le Graverand
authors.forename: K D
authors.initials: KD
authors.lastname: Brandt
authors.forename: S A
authors.initials: SA
authors.lastname: Mazzuca
authors.forename: B P
authors.initials: BP
authors.lastname: Katz
authors.forename: R
authors.initials: R
authors.lastname: Buck
authors.forename: K A
authors.initials: KA
authors.lastname: Lane
authors.forename: E
authors.initials: E
authors.lastname: Pickering
authors.forename: O V
authors.initials: OV
authors.lastname: Nemirovskiy
authors.forename: T
authors.initials: T
authors.lastname: Sunyer
authors.forename: D J
authors.initials: DJ
authors.lastname: Welsch
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000652:urine; D015992:Body Mass Index; D024043:Collagen Type II / Q000276:immunology / Q000652:urine*; D003401:Creatine / Q000652:urine; D004318:Doxycycline / Q000627:therapeutic use; D000939:Epitopes / Q000276:immunology / Q000652:urine*; D005260:Female; D006801:Humans; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology*; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000276:immunology / Q000652:urine; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000652:urine*; D011237:Predictive Value of Tests; D011859:Radiography; D015203:Reproducibility of Results
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D024043:Collagen Type II; D000939:Epitopes; D003401:Creatine; D004318:Doxycycline