title: Disease-modifying effect of strontium ranelate in a subset of patients from the Phase III knee osteoarthritis study SEKOIA using quantitative MRI: reduction in bone marrow lesions protects against cartilage loss.
abstract: OBJECTIVE
  To explore, using MRI, the disease-modifying effect of strontium ranelate (SrRan) treatment on cartilage volume loss (CVL) and bone marrow lesions (BMLs) in a subset of patients from a Phase III clinical trial in knee osteoarthritis (OA) (SrRan Efficacy in Knee OsteoarthrItis triAl (SEKOIA)).
  
  
  METHODS
  Patients with primary symptomatic knee OA were randomised to receive either SrRan 1 g/day or 2 g/day or placebo (SEKOIA study). A subset of these patients had MRIs at baseline, 12, 24 and 36 months to assess the knee cartilage volume and BMLs. Missing values were imputed and the analyses were adjusted according to Bonferroni.
  
  
  RESULTS
  In this MRI subset, the distribution of patients (modified intention-to-treat; n=330) was 113, 105 and 112 for SrRan 1 g/day, 2 g/day and placebo, respectively. The groups were fairly balanced at baseline regarding demographics, clinical symptoms or imaging characteristics. Treatment with SrRan 2 g/day significantly decreased CVL on the plateaus at 12 (p=0.002) and 36 (p=0.003) months compared with placebo. Of note, in the medial femur and plateau, SrRan 1 g/day, but not SrRan 2 g/day, had more CVL than placebo. In patients with BML in the medial compartment at baseline, the BML score at 36 months was decreased in both treatment groups compared with the placebo group (SrRan 1 g/day, p=0.002 and SrRan 2 g/day p=0.001, respectively), and CVL significantly decreased with SrRan 2 g/day (p=0.023) in the plateau compared with placebo.
  
  
  CONCLUSIONS
  In knee OA patients, treatment with SrRan 2 g/day was found to have beneficial effects on structural changes by significantly reducing CVL in the plateau and BML progression in the medial compartment.
authors.affiliation: Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Montreal, Quebec, Canada.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Pelletier
authors.affiliation: Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Montreal, Quebec, Canada.
authors.forename: Camille
authors.initials: C
authors.lastname: Roubille
authors.affiliation: Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Montreal, Quebec, Canada.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Raynauld
authors.affiliation: Imaging Research & Development, ArthroLab Inc., Montreal, Quebec, Canada.
authors.forename: François
authors.initials: F
authors.lastname: Abram
authors.affiliation: StatSciences Inc., Notre-Dame de l'Île-Perrot, Quebec, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Dorais
authors.affiliation: Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Montreal, Quebec, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Delorme
authors.affiliation: Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Montreal, Quebec, Canada.
authors.forename: Johanne
authors.initials: J
authors.lastname: Martel-Pelletier
mesh_terms: D000328:Adult; D000368:Aged; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology*; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000473:pathology; D013876:Thiophenes / Q000627:therapeutic use*
chemical_list: D050071:Bone Density Conservation Agents; D013876:Thiophenes; C081587:strontium ranelate
keywords: Knee Osteoarthritis; Magnetic Resonance Imaging; Osteoarthritis