The aim of the strontium ranelate (SR) for treatment of osteoporosis (STRATOS) trial was to investigate the efficacy and safety of different doses of SR, a novel agent in the treatment of postmenopausal osteoporosis. A randomized, multicenter, double-blind, placebo-controlled trial was undertaken in 353 osteoporotic women with at least one previous vertebral fracture and a lumbar T-score <-2.4. Patients were randomized to receive placebo, 0.5 g, 1 g, or 2 g SR/d for 2 yr. The primary efficacy endpoint was lumbar bone mineral density (BMD), assessed by dual-energy x-ray absorptiometry. Secondary outcome measures included femoral BMD, incidence of new vertebral deformities, and biochemical markers of bone metabolism. Lumbar BMD, adjusted for bone strontium content, increased in a dose-dependent manner in the intention-to-treat population: mean annual slope increased from 1.4% with 0.5 g/d SR to 3.0% with 2 g/d SR, which was significantly higher than placebo (P < 0.01). There was a significant reduction in the number of patients experiencing new vertebral deformities in the second year of treatment with 2 g/d SR [relative risk 0.56; 95% confidence interval (0.35; 0.89)]. In the 2 g/d group, there was a significant increase in serum levels of bone alkaline phosphatase, whereas urinary excretion of cross-linked N-telopeptide, a marker of bone resorption, was lower with SR than with placebo. All tested doses were well tolerated; the 2 g/d dose was considered to offer the best combination of efficacy and safety. In conclusion, SR therapy increased vertebral BMD and reduced the incidence of vertebral fractures.