Strontium ranelate phase 2 dose-ranging studies: PREVOS and STRATOS studies

Abstract

The aim of the PREVOS study (PREVention Of early postmenopausal bone loss by Strontium ranelate) and the STRATOS study (STRontium Administration for Treatment of OSteoporosis) was to determine the minimum dose at which strontium ranelate (SR) is effective in, respectively, the prevention of bone loss in early postmenopausal nonosteoporotic women and the treatment of postmenopausal vertebral osteoporosis. Both studies were randomized, double-blind, placebo-controlled, dose-finding studies in parallel groups and lasted 2 years. In the PREVOS study, 160 early postmenopausal women were randomized to receive placebo, SR 125 mg/day, 500 mg/day or 1 g/day. In the STRATOS study, 353 osteoporotic postmenopausal women with at least one previous vertebral fracture and a lumbar T-score <-2.4 were randomized to receive placebo, SR 500 mg/day, 1 g/day or 2 g/day. In both studies, the primary efficacy parameter was lumbar bone mineral density (BMD) measured by dual-energy X-ray absorptiometry. Secondary efficacy criteria included incidence of new vertebral deformities (in the STRATOS study only) and biochemical markers of bone metabolism. In the PREVOS study, the increase in lumbar BMD from baseline in the 1 g/day group (+5.53%) was significantly different from the decrease in the placebo group ( p<0.001). In the STRATOS study, the annual increase in lumbar BMD in the 2 g/day group (+7.3% per year) was significantly higher than in the placebo group ( p<0.001). There was a significant reduction in the number of patients experiencing new vertebral deformities in the second year of treatment in the 2 g/day group (relative risk: 0.56; 95% confidence interval: 0.35, 0.89). In both studies, there was a significant increase in the bone formation marker (bone alkaline phosphatase) in the higher-dose group. Urinary excretion of the marker of bone resorption (cross-linked N-telopeptide) was lower with SR than with placebo in the STRATOS study. SR was very well tolerated in both studies. The minimum dose at which SR is effective in preventing bone loss in early postmenopausal nonosteoporotic women and in the treatment of postmenopausal osteoporosis is 1 g/day and 2 g/day, respectively.