title: Meniscal extrusion promotes knee osteoarthritis structural progression: protective effect of strontium ranelate treatment in a phase III clinical trial.
abstract: BACKGROUND
  To evaluate the impact of meniscal extrusion (Ext) on knee osteoarthritis (OA) structural progression and on response to strontium ranelate (SrRan) treatment at 36 months in patients with (+) or without (-) Ext, in association (+) or not (-) with bone marrow lesions (BML) in the medial compartment using X-rays (JSW) and qMRI.
  
  
  METHODS
  Patients from the qMRI substudy of the SEKOIA trial (SrRan 1 g/day, n = 113; SrRan 2 g/day, n = 105; placebo, n = 112) were stratified based on whether meniscal extrusion and/or BML were present or not in the medial compartment.
  
  
  RESULTS
  In the placebo group, Ext+ patients (n = 26) had more JSW loss (p = 0.002) and cartilage volume loss in the global knee (p = 0.034) and plateau (p = 0.005), and medial compartment (p = 0.0005) than Ext- patients (n = 86). Ext-BML+ patients (n = 18) demonstrated more JSW loss (p = 0.003) and cartilage volume loss in the global (p = 0.020) and medial femur (p = 0.055) than Ext-BML- (n = 68). Compared to Ext+ BML- (n = 14), Ext+ BML+ patients (n = 12) had more cartilage volume loss in the global femur (p = 0.028), with no change in JSW. The JSW loss (p = 0.0004) and cartilage volume loss (global knee, p = 0.033, medial compartment, p = 0.0005) were greater when Ext and BML were simultaneously present in the medial compartment. SrRan 2 g/day treatment demonstrated a reduction in OA knee structural progression with qMRI, but not with JSW, in which less cartilage volume loss was found in the plateaus (p = 0.007) in Ext+ patients (n = 15), and in the medial plateau (p = 0.046) in patients in whom both Ext and BML were co-localized.
  
  
  CONCLUSIONS
  The findings of this study are novel and could have an impact on future strategies regarding clinical trials. Indeed, data first argue for a combined, cumulative effect of meniscal extrusion and bone marrow lesions on cartilage loss and, secondly, they showed that SrRan may have protective effects in OA patients with meniscal extrusion as well as when both meniscal extrusion and BML are co-localized.
authors.affiliation: Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), 900 Saint-Denis, Pavillon R, Suite R11.412A, Montreal, Quebec, H2X 0A9, Canada. camille.roubille@gmail.com.
authors.forename: Camille
authors.initials: C
authors.lastname: Roubille
authors.affiliation: Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), 900 Saint-Denis, Pavillon R, Suite R11.412A, Montreal, Quebec, H2X 0A9, Canada. jm@martelpelletier.ca.
authors.forename: Johanne
authors.initials: J
authors.lastname: Martel-Pelletier
authors.affiliation: Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), 900 Saint-Denis, Pavillon R, Suite R11.412A, Montreal, Quebec, H2X 0A9, Canada. jp.raynauld@videotron.ca.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Raynauld
authors.affiliation: Medical Imaging Research & Development, ArthroLab Inc, Montreal, Quebec, Canada. fabram@arthrovision.biz.
authors.forename: François
authors.initials: F
authors.lastname: Abram
authors.affiliation: StatSciences Inc, Notre-Dame-de-l'Île-Perrot, Quebec, Canada. marc.dorais@statsciences.net.
authors.forename: Marc
authors.initials: M
authors.lastname: Dorais
authors.affiliation: Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), 900 Saint-Denis, Pavillon R, Suite R11.412A, Montreal, Quebec, H2X 0A9, Canada. pdelorme@arthrolab.com.
authors.forename: Philippe
authors.initials: P
authors.lastname: Delorme
authors.affiliation: Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), 900 Saint-Denis, Pavillon R, Suite R11.412A, Montreal, Quebec, H2X 0A9, Canada. dr@jppelletier.ca.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Pelletier
mesh_terms: D000368:Aged; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008592:Menisci, Tibial / Q000473:pathology*; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000175:diagnosis* / Q000188:drug therapy*; D013876:Thiophenes / Q000627:therapeutic use*
chemical_list: D050071:Bone Density Conservation Agents; D013876:Thiophenes; C081587:strontium ranelate