title: Analysis of the precision and sensitivity to change of different approaches to assess cartilage loss by quantitative MRI in a longitudinal multicentre clinical trial in patients with knee osteoarthritis.
abstract: BACKGROUND
  Cartilage thickness and volume loss measurements using quantitative magnetic resonance imaging (qMRI) are suggested to detect significant cartilage changes over short time intervals. We aimed to compare these two different approaches looking at the global knee and subregions, using data from an osteoarthritis (OA) multicentre randomised clinical trial.
  
  
  METHODS
  Three hundred and fifty-five patients with symptomatic knee OA were recruited for a two-year, double-blind, randomised clinical trial evaluating the effect of 200 mg licofelone twice daily and 500 mg naproxen twice daily on cartilage loss, and 301 patients had baseline MRI. MRIs were performed at baseline, 6, 12 and 24 months. Cartilage volume and thickness in the global joint, medial and lateral compartments, and central weight-bearing subregions of the medial and lateral femoral condyles and tibial plateaus were analysed. Data were analysed for the mean value imputed for intent-to-treat (ITT-MVI) and statistical analyses were performed using two-sample Student's t-test.
  
  
  RESULTS
  Cartilage mean thickness loss in the global joint, lateral and medial compartments, as well as in medial compartments stratified according to patients with or without meniscal extrusion, was significantly less in the licofelone compared with the naproxen group at 12 and 24 months. Interestingly, these data were similar to those found when using cartilage volume loss as an outcome. Although greater cartilage volume and mean thickness loss was seen in central weight-bearing subregions of the medial and lateral compartments compared with the whole compartment and also in patients with meniscal lesions/extrusion, suggesting good sensitivity to change, its high standard deviation precluded for the condyles a high statistical power and abrogated statistically significant differences between the treatment groups.
  
  
  CONCLUSIONS
  These data demonstrate that both the measurement of cartilage thickness and that of cartilage volume provide the same level of sensitivity to estimate cartilage loss in a clinical trial. However, the potential of gaining statistical power with the use of thickness/volume change in knee subregions as an outcome seems negated by high inter-patient variability. Moreover, there is no superiority in statistical power by selecting patients with meniscal extrusion.
authors.affiliation: Osteoarthritis Research Unit, University of Montreal Hospital Centre, Notre-Dame Hospital, Montreal, Quebec, Canada. jp.raynauld@videotron.ca
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Raynauld
authors.forename: Johanne
authors.initials: J
authors.lastname: Martel-Pelletier
authors.forename: François
authors.initials: F
authors.lastname: Abram
authors.forename: Marc
authors.initials: M
authors.lastname: Dorais
authors.forename: Boulos
authors.initials: B
authors.lastname: Haraoui
authors.forename: Denis
authors.initials: D
authors.lastname: Choquette
authors.forename: Peter
authors.initials: P
authors.lastname: Bias
authors.forename: Karl H
authors.initials: KH
authors.lastname: Emmert
authors.forename: Stefan
authors.initials: S
authors.lastname: Laufer
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Pelletier
mesh_terms: D002358:Cartilage, Articular / Q000473:pathology*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods* / Q000592:standards*; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000627:therapeutic use; D020370:Osteoarthritis, Knee / Q000188:drug therapy / Q000473:pathology*; D011758:Pyrroles / Q000627:therapeutic use; D012680:Sensitivity and Specificity
chemical_list: D011758:Pyrroles; D009288:Naproxen; C088092:licofelone