title: Efficacy and safety of oral strontium ranelate for the treatment of knee osteoarthritis: rationale and design of randomised, double-blind, placebo-controlled trial.
abstract: OBJECTIVE
  The osteoporosis drug strontium ranelate dissociates bone remodelling processes. It also inhibits subchondral bone resorption and stimulates cartilage matrix formation in vitro. Exploratory studies in the osteoporosis trials report that strontium ranelate reduces biomarkers of cartilage degradation, and attenuates the progression and clinical symptoms of spinal osteoarthritis, suggesting symptom- and structure-modifying activity in osteoarthritis. We describe the rationale and design of a randomised trial evaluating the efficacy and safety of strontium ranelate in knee osteoarthritis.
  This double-blind, placebo-controlled trial (98 centres, 18 countries) includes ambulatory Caucasian men and women aged ≥50 years with primary knee osteoarthritis of the medial tibiofemoral compartment (Kellgren and Lawrence grade 2 or 3), joint space width (JSW) 2.5 to 5 mm, and knee pain on most days in the previous month (intensity ≥40 mm on a visual analogue scale). Patients are randomly allocated to three groups (strontium ranelate 1 or 2 g/day, or placebo). Follow-up is expected to last 3 years. The primary endpoint is radiographic change in JSW from baseline in each group versus placebo. The main clinical secondary endpoint is WOMAC score at the knee. Safety is assessed at every visit. It is estimated that 1600 patients are required to establish statistical significance with power >90% (0.2 mm ± 10% between-group difference in change in JSW over 3 years). Recruitment started in April 2006. The results are expected in spring 2012.
  
  
  BACKGROUND
  The trial is registered on www.controlled-trials.com (number ISRCTN41323372).
  
  
  CONCLUSIONS
  This randomised, double blind, placebo-controlled study will establish the potential of strontium ranelate in improving structure and symptoms in patients with knee osteoarthritis.
authors.affiliation: MRC Lifecourse Epidemiology Unit, University of Southampton and NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, UK. cc@mrc.soton.ac.uk
authors.forename: Cyrus
authors.initials: C
authors.lastname: Cooper
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Reginster
authors.forename: Roland
authors.initials: R
authors.lastname: Chapurlat
authors.forename: Claus
authors.initials: C
authors.lastname: Christiansen
authors.forename: Harry
authors.initials: H
authors.lastname: Genant
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bellamy
authors.forename: William
authors.initials: W
authors.lastname: Bensen
authors.forename: Federico
authors.initials: F
authors.lastname: Navarro
authors.forename: Janusz
authors.initials: J
authors.lastname: Badurski
authors.forename: Evgeny
authors.initials: E
authors.lastname: Nasonov
authors.forename: Xavier
authors.initials: X
authors.lastname: Chevalier
authors.forename: Philip N
authors.initials: PN
authors.lastname: Sambrook
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007719:Knee Joint; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D012107:Research Design; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D050071:Bone Density Conservation Agents; D009942:Organometallic Compounds; D013876:Thiophenes; C081587:strontium ranelate