A meta-analysis of the efficacy of raloxifene on all clinical and vertebral fractures and its dependency on FRAX

Introduction: Multiple Outcomes of Raloxifene Evaluation (MORE), a placebo controlled phase III study of raloxifene in postmenopausal osteoporosis, showed that both doses tested (60 mg and 120 mg daily) reduced the risk of vertebral fracture. There was no significant effect on non-vertebral fracture.

Aims: The aim of the present study was to evaluate the distribution of fracture risk assessed at baseline using the FRAX tool in MORE and to determine the efficacy of raloxifene as a function of baseline fracture risk. The effects of raloxifene (60 and 120 mg daily combined) with placebo on the risk of all clinical fractures as well as the risk of morphometric vertebral fracture were examined as a function of baseline fracture risk.

Methods: Baseline clinical risk factors and BMD were entered in the FRAX model to compute the 10-year probability of major osteoporotic fractures. The interaction between fracture probability and treatment efficacy was examined by Poisson regression.

Results: The 10-year probability of major osteoporotic fractures (with BMD) ranged from 0.9% to 77.2%. The incidence of clinical fractures and morphometric vertebral fractures increased with increasing baseline fracture probabilities. Treatment with raloxifene was associated with an 18% decrease in all clinical fractures compared to placebo treatment (hazard ratio HR=0.82; 95% CI=0.71-0.95; p=0.0063) and a 42% decrease in incident morphometric vertebral fractures (HR=0.58; 95% CI=0.48-0.69; p<0.001). Efficacy was shown over the whole range of fracture probability and the interaction between fracture probability and treatment was not significant. The efficacy or raloxifene on vertebral fracture risk was significantly greater at lower ages. At the 90th percentile of age (75 years) vertebral fracture risk was reduced by 31% irrespective of FRAX probabilities. In contrast at younger ages, efficacy was higher and increased further still with decreasing fracture probability.

Conclusion: We conclude that raloxifene (60 and 120 mg doses combined) significantly decreased the risk of all clinical fractures and morphometric fractures in women. Overall, there was no significant interaction between efficacy and fracture probability. In the case of morphometric vertebral fractures efficacy decreased significantly with increasing age.