Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial
- Jean-Yves Reginster1,
- Janusz Badurski2,
- Nicholas Bellamy3,
- William Bensen4,
- Roland Chapurlat5,
- Xavier Chevalier6,
- Claus Christiansen7,
- Harry Genant8,
- Federico Navarro9,
- Evgeny Nasonov10,
- Philip N Sambrook11,
- Timothy D Spector12,
- Cyrus Cooper13
- 1Department of Public Health Epidemiology and Health Economics, University of Liege, Liege, Belgium
- 2Centre of Osteoporosis and Osteoarticular Diseases, Bialystok, Poland
- 3Centre of National Research on Disability (CONROD), University of Queensland, Herston, Queensland, Australia
- 4DeGroot School of Medicine, McMaster University Hamilton, Hamilton, Ontario, Canada
- 5INSERM UMR 1033, Service de Rhumatologie et Pathologie Osseuse, Hôpital Edouard Herriot, Université de Lyon, Lyon, France
- 6Service de Rhumatologie, Hôpital Henri Mondor, Créteil, France
- 7Synarc, Centre for Clinical and Basic Research (CCBR), Ballerup, Denmark
- 8Radiology, Medicine, Epidemiology and Orthopedic Surgery, University of California, San Francisco and Synarc, San Francisco, California, USA
- 9Rheumatology Department, Hospital Universitario Virgen Macarena, Sevilla, Spain
- 10State Institute of Rheumatology, Russian Academy of Medical Sciences, Moscow, Russian Federation
- 11Institute of Bone and Joint Research, Royal North Shore Hospital, St Leonards, NSW, Australia
- 12Department of Twin Research and Genetic Epidemiology, Kings College London, St Thomas’ Hospital, London, UK
- 13MRC Lifecourse Epidemiology Unit, NIHR Musculoskeletal Biomedical Research Unit, University of Southampton, University of Oxford, Oxford, UK
- Correspondence to Professor Jean-Yves Reginster, Department of Public Health and Health Economics, University of Liege, 4020 Liege, Belgium; jyreginster{at}ulg.ac.be
- Accepted 13 September 2012
- Published Online First 1 November 2012
Abstract
Background Strontium ranelate is currently used for osteoporosis. The international, double-blind, randomised, placebo-controlled Strontium ranelate Efficacy in Knee OsteoarthrItis triAl evaluated its effect on radiological progression of knee osteoarthritis.
Methods Patients with knee osteoarthritis (Kellgren and Lawrence grade 2 or 3, and joint space width (JSW) 2.5–5 mm) were randomly allocated to strontium ranelate 1 g/day (n=558), 2 g/day (n=566) or placebo (n=559). The primary endpoint was radiographical change in JSW (medial tibiofemoral compartment) over 3 years versus placebo. Secondary endpoints included radiological progression, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and knee pain. The trial is registered (ISRCTN41323372).
Results The intention-to-treat population included 1371 patients. Treatment with strontium ranelate was associated with smaller degradations in JSW than placebo (1 g/day: −0.23 (SD 0.56) mm; 2 g/day: −0.27 (SD 0.63) mm; placebo: −0.37 (SD 0.59) mm); treatment-placebo differences were 0.14 (SE 0.04), 95% CI 0.05 to 0.23, p<0.001 for 1 g/day and 0.10 (SE 0.04), 95% CI 0.02 to 0.19, p=0.018 for 2 g/day. Fewer radiological progressors were observed with strontium ranelate (p<0.001 and p=0.012 for 1 and 2 g/day). There were greater reductions in total WOMAC score (p=0.045), pain subscore (p=0.028), physical function subscore (p=0.099) and knee pain (p=0.065) with strontium ranelate 2 g/day. Strontium ranelate was well tolerated.
Conclusions Treatment with strontium ranelate 1 and 2 g/day is associated with a significant effect on structure in patients with knee osteoarthritis, and a beneficial effect on symptoms for strontium ranelate 2 g/day.
