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

Body, J.-J.; Marin, F.; Kendler, D. L.; Zerbini, C. A. F.; López-Romero, P.; Möricke, R.; Casado, E.; Fahrleitner-Pammer, A.; Stepan, J. J.; Lespessailles, E.; Minisola, S.; Geusens, P.

Affiliations

¹CHU Brugmann, Université Libre de Bruxelles (ULB), Brussels, Belgium

²Lilly Research Center Europe, Madrid, Spain

³University of British Columbia, Vancouver, Canada

⁴Centro Paulista de Investigaçao Clínica, Sao Paulo, Brazil

⁵Institut Präventive Medizin & Klinische Forschung, Magdeburg, Germany

⁶University Hospital Parc Taulí Sabadell, Barcelona, Spain

⁷Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria

⁸Institute of Rheumatology and Faculty of Medicine 1, Charles University, Prague, Czech Republic

⁹Regional Hospital, University of Orleans, Orleans, France

¹⁰Sapienza Rome University, Rome, Italy

¹¹Maastricht University Medical Center, Maastricht, The Netherlands

Abstract and keywords

Summary: 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; Fractures; FRAX®\n; Osteoporosis; Risedronate; Teriparatide

Links

DOI: 10.1007/s00198-020-05463-4

PubMed: 32474650

WoS: 000536417900001

History

Received: 2020-02-25

Accepted: 2020-05-11

Online: 2020-05-30

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