Efficacy and safety of oral strontium ranelate for the treatment of knee osteoarthritis: rationale and design of randomised, double-blind, placebo-controlled trial

Curr Med Res Opin. 2012 Feb;28(2):231-9. doi: 10.1185/03007995.2011.648758. Epub 2012 Jan 17.


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.

Research design, methods, and results: 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.

Clinical trial registration: 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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Density Conservation Agents / administration & dosage
  • Bone Density Conservation Agents / adverse effects*
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Remodeling / drug effects
  • Disease Progression
  • Double-Blind Method
  • Female
  • Humans
  • Knee Joint
  • Male
  • Middle Aged
  • Organometallic Compounds / administration & dosage
  • Organometallic Compounds / adverse effects*
  • Organometallic Compounds / therapeutic use*
  • Osteoarthritis, Knee / drug therapy*
  • Research Design
  • Thiophenes / administration & dosage
  • Thiophenes / adverse effects*
  • Thiophenes / therapeutic use*


  • Bone Density Conservation Agents
  • Organometallic Compounds
  • Thiophenes
  • strontium ranelate

Associated data

  • ISRCTN/ISRCTN41323372