title: Clinically meaningful effect of strontium ranelate on symptoms in knee osteoarthritis: a responder analysis.
abstract: OBJECTIVE
  The aim of this study was to assess the efficacy of strontium ranelate in improving symptoms in knee OA.
  
  
  METHODS
  Symptoms were assessed over 3 years in patients with primary knee OA receiving strontium ranelate 2 g/day (n = 454), 1 g/day (n = 445) or placebo (n = 472) in the Strontium Ranelate Efficacy in Knee Osteoarthritis Trial. Clinical response was evaluated using WOMAC subscores, minimal perceptible clinical improvement (MPCI), minimal clinically important improvement (MCII) and a modified OMERACT-Osteoarthritis Research Society International (OARSI) responder definition. Patients who withdrew prematurely from the study were considered non-responders.
  
  
  RESULTS
  There was no significant effect on symptoms for strontium ranelate 1 g/day. At the dosage of 2 g/day, strontium ranelate was associated with greater response than placebo in terms of ≥20% improvement in WOMAC pain from baseline to the last visit (58% vs 47%, P = 0.002) and ≥50% improvement in WOMAC pain (42% vs 36%, P = 0.083). Significant differences were found in MPCI response for WOMAC pain (52% vs 40%, P < 0.001), stiffness (47% vs 39%, P = 0.009) and physical function (46% vs 37%, P = 0.009) and in MCII response for WOMAC physical function (46% vs 37%, P = 0.013). There were also more OMERACT-OARSI-like responders with strontium ranelate (44% vs 35%, P = 0.004). The treatment-placebo difference in MPCI response for WOMAC pain was significant after 6 months (P = 0.024), while that in MPCI and MCII response for WOMAC physical function reached significance after 12 months (P = 0.027 and P = 0.019, respectively).
  
  
  CONCLUSIONS
  Treatment with strontium ranelate 2 g/day over 3 years is associated with a clinically meaningful improvement in pain from 6 months as well as physical function and stiffness as assessed by the number of responders above thresholds of clinical relevance.
  
  
  BACKGROUND
  Current Controlled Trials. http://www.controlled-trials.com/ (ISRCTN41323372).
authors.affiliation: Department of Public Health, Epidemiology and Health Economics, University of Liège, CHU Sart-Tilman, Liège, Belgium, School of Medicine, University of Queensland, Herston, Queensland, Australia, INSERM UMR 1033 and Université de Lyon, Service de Rhumatologie et Pathologie Osseuse, Hôpital Edouard Herriot, Lyon, France, Université Paris 7, UFR médicale, Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Fédération de Rhumatologie, Paris Cedex, France and MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, and NIHR Biomedical Research Unit, University of Oxford, Oxford, UK. olivier.bruyere@ulg.ac.be.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bruyère
authors.affiliation: Department of Public Health, Epidemiology and Health Economics, University of Liège, CHU Sart-Tilman, Liège, Belgium, School of Medicine, University of Queensland, Herston, Queensland, Australia, INSERM UMR 1033 and Université de Lyon, Service de Rhumatologie et Pathologie Osseuse, Hôpital Edouard Herriot, Lyon, France, Université Paris 7, UFR médicale, Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Fédération de Rhumatologie, Paris Cedex, France and MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, and NIHR Biomedical Research Unit, University of Oxford, Oxford, UK.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Reginster
authors.affiliation: Department of Public Health, Epidemiology and Health Economics, University of Liège, CHU Sart-Tilman, Liège, Belgium, School of Medicine, University of Queensland, Herston, Queensland, Australia, INSERM UMR 1033 and Université de Lyon, Service de Rhumatologie et Pathologie Osseuse, Hôpital Edouard Herriot, Lyon, France, Université Paris 7, UFR médicale, Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Fédération de Rhumatologie, Paris Cedex, France and MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, and NIHR Biomedical Research Unit, University of Oxford, Oxford, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bellamy
authors.affiliation: Department of Public Health, Epidemiology and Health Economics, University of Liège, CHU Sart-Tilman, Liège, Belgium, School of Medicine, University of Queensland, Herston, Queensland, Australia, INSERM UMR 1033 and Université de Lyon, Service de Rhumatologie et Pathologie Osseuse, Hôpital Edouard Herriot, Lyon, France, Université Paris 7, UFR médicale, Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Fédération de Rhumatologie, Paris Cedex, France and MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, and NIHR Biomedical Research Unit, University of Oxford, Oxford, UK.
authors.forename: Roland
authors.initials: R
authors.lastname: Chapurlat
authors.affiliation: Department of Public Health, Epidemiology and Health Economics, University of Liège, CHU Sart-Tilman, Liège, Belgium, School of Medicine, University of Queensland, Herston, Queensland, Australia, INSERM UMR 1033 and Université de Lyon, Service de Rhumatologie et Pathologie Osseuse, Hôpital Edouard Herriot, Lyon, France, Université Paris 7, UFR médicale, Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Fédération de Rhumatologie, Paris Cedex, France and MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, and NIHR Biomedical Research Unit, University of Oxford, Oxford, UK.
authors.forename: Pascal
authors.initials: P
authors.lastname: Richette
authors.affiliation: Department of Public Health, Epidemiology and Health Economics, University of Liège, CHU Sart-Tilman, Liège, Belgium, School of Medicine, University of Queensland, Herston, Queensland, Australia, INSERM UMR 1033 and Université de Lyon, Service de Rhumatologie et Pathologie Osseuse, Hôpital Edouard Herriot, Lyon, France, Université Paris 7, UFR médicale, Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Fédération de Rhumatologie, Paris Cedex, France and MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, and NIHR Biomedical Research Unit, University of Oxford, Oxford, UK.
authors.forename: Cyrus
authors.initials: C
authors.lastname: Cooper
mesh_terms: D000368:Aged; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D013876:Thiophenes / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; D013876:Thiophenes; C081587:strontium ranelate
keywords: SEKOIA; osteoarthritis; pain; responder criteria; strontium ranelate; symptoms