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

Abstract

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.

Keywords: Bisphosphonates; FRAX®; Fractures; Osteoporosis; Risedronate; Teriparatide.

Conflict of interest statement

Jean-Jacques Body: consultant fees from Amgen, Sandoz, and UCB; research support from Lilly. Fernando Marin: employee, Lilly. David L. Kendler: honoraria, research grants, and/or consultant fees from Amgen, Lilly, Radius, and Pfizer. Cristiano A.F. Zerbini: research support from Lilly. Pedro López-Romero: employee, Lilly. Rüdiger Möricke: none. Enrique Casado: speaker and/or consultant fees from Amgen, Lilly, UCB, and Theramex. Astrid Fahrleitner-Pammer: speaker fees from Amgen, Alexion, BMS, Lilly, Fresenius, Sandoz, Shire, and UCB. Jan J. Stepan: none. Eric Lespessailles: speaker and consultant fees from Amgen, Expanscience, Lilly, and MSD; research grants from Abbvie, Amgen, Lilly, MSD, and UCB. Salvatore Minisola: speaker and/or consultant fees from Abiogen, Amgen, DiaSorin, Lilly, Italfarmaco, Fujii, MSD, and Takeda. Piet Geusens: consultant and/or speaker fees from Lilly, and research support from Pfizer, Abbott, Lilly, Amgen, MSD, Roche, UCB, BMS, Mylan, and Novartis.

Figures

Fig. 1

Kaplan-Meier estimates of the cumulative incidence of the first FRAX®-defined major osteoporotic fracture. *p value from the stratified log-rank test adjusted for antecedent of recent clinical vertebral fractures and recent bisphosphonate use

Fig. 2

Incidence rates of FRAX®-defined major osteoporotic fracture (number of events per 100 patient-years) by 6-month periods and overall (0 to 24 months). Note: the incidence rates during each of the four 6-month period intervals are calculated as the number of patients who experienced at least one fracture event in the respective 6-month period, divided by the total amount of person-time contributed by the population at risk during the respective time interval. The overall incidence rate is estimated from 0 to 24 months

Fig. 3

Incidence rates of pooled clinical fractures (clinical vertebral and non-vertebral) (number of events per 100 patient-years) by 6-month periods and overall (0 to 24 months). Note: data are presented as incidence rate. The incidence rate is calculated as the number of patients who experienced at least one fracture event in the respective 6-month period, divided by the total amount of person-time contributed by the population at risk during the respective time interval.