Efficacy of teriparatide compared with risedronate on FRAX-defined major osteoporotic fractures: results of the VERO clinical trial.

UNLABELLED

FRAX calculates the 10-year probability of major osteoporotic fractures (MOF), which are considered to have a greater clinical impact than other fractures. Our results suggest that, in postmenopausal women with severe osteoporosis, those treated with teriparatide had a 60% lower risk of FRAX-defined MOF compared with those treated with risedronate.

INTRODUCTION

The VERO trial was an active-controlled fracture endpoint clinical trial that enrolled postmenopausal women with severe osteoporosis. After 24 months, a 52% reduction in the hazard ratio (HR) of clinical fractures was reported in patients randomized to teriparatide compared with risedronate. We examined fracture results restricted to FRAX-defined major osteoporotic fractures (MOF), which include clinical vertebral, hip, humerus, and forearm fractures.

METHODS

In total, 1360 postmenopausal women (mean age 72.1 years) were randomized to receive subcutaneous daily teriparatide (20 μg) or oral weekly risedronate (35 mg). Patient cumulative incidence of ≥ 1 FRAX-defined MOF and of all clinical fractures were estimated by Kaplan-Meier analyses, and the comparison between treatments was based on the stratified log-rank test. Additionally, an extended Cox model was used to estimate HRs at different time points. Incidence fracture rates were estimated at each 6-month interval.

RESULTS

After 24 months, 16 (2.6%) patients in the teriparatide group had ≥ 1 low trauma FRAX-defined MOF compared with 40 patients (6.4%) in the risedronate group (HR 0.40; 95% CI 0.23-0.68; p = 0.001). Clinical vertebral and radius fractures were the most frequent FRAX-defined MOF sites. The largest difference in incidence rates of both FRAX-defined MOF and all clinical fractures between treatments occurred during the 6- to 12-month period. There was a statistically significant reduction in fractures between groups as early as 7 months for both categories of clinical fractures analyzed.

CONCLUSION

In postmenopausal women with severe osteoporosis, treatment with teriparatide was more efficacious than risedronate, with a 60% lower risk of FRAX-defined MOF during the 24-month treatment period. Fracture risk was statistically significantly reduced at 7 months of treatment.

CLINICAL TRIAL INFORMATION

ClinicalTrials.gov Identifier: NCT01709110 EudraCT Number: 2012-000123-41.