A meta-analysis of the effect of strontium ranelate on the risk of vertebral and non-vertebral fracture in postmenopausal osteoporosis and the interaction with FRAX®

The aim of the present study was to determine the efficacy of strontium ranelate as a function of baseline fracture risk. Treatment with strontium ranelate was associated with a significant 31% decrease in all clinical osteoporotic fractures (vertebral fractures included). Hazard ratios for the effect of strontium ranelate on the fracture outcome did not change significantly with increasing fracture probability. Introduction Two previous studies have suggested that the efficacy of intervention may be greater in the segment of the population at highest fracture risk as assessed by the FRAX (R) algorithms. The aim of the present study was to determine whether the anti-fracture efficacy of strontium ranelate was dependent of the level of fracture risk. Methods The primary data of the two phase III studies (SOTI and TROPOS) of the effects of strontium ranelate in postmenopausal osteoporosis were combined. Country-specific probabilities were computed using the FRAX (R) tool (version 2.0). The primary outcome variable comprised all clinical osteoporotic fractures (including clinical vertebral fractures). Interactions between fracture probability and efficacy were explored by Poisson regression. Results The 10-year probability of major osteoporotic fractures (with BMD) ranged from 2.5% to 90.8%. FRAX (R)-based hip fracture probabilities ranged from 0.1% to 90.3%. The incidence of clinical osteoporotic fractures (vertebral fractures excluded) and morphometric vertebral fractures increased with increasing baseline fracture probabilities. Treatment with strontium ranelate was associated with a 31% (95% CI=20-39%) decrease in osteoporotic clinical fractures and a 40% decrease in vertebral fractures assessed by semiquantitative morphometry (95% CI=31-48%) Hazard ratios for the effect of strontium ranelate on the fracture outcomes did not change significantly with increasing fracture probability. Conclusion Strontium ranelate significantly decreased the risk of osteoporotic clinical fractures, non vertebral fractures and morphometric vertebral fractures in women. Overall, the efficacy of strontium ranelate was not dependent of the level of fracture risk assessed by FRAX