Serum 25-hydroxy-vitamin D and the risk of fractures in the teriparatide versus risedronate VERO clinical trial
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Using data from the 2-year, randomized, double-dummy VERO trial, we examined the changes in 25-hydroxy-vitamin D (25[OH]D) concentrations over time, and whether the fracture risk reduction of teriparatide versus risedronate varies by baseline 25(OH)D sufficiency category.
Postmenopausal women with established osteoporosis received subcutaneous daily teriparatide 20 μg or oral weekly risedronate 35 mg, with concomitant 500–1000 mg of elemental calcium and 400–800 IU/day of vitamin D supplements. Fracture endpoints were analyzed by predefined subgroups of 25(OH)D insufficient and sufficient patients. Heterogeneity of the treatment effect on fractures was investigated by logistic and Cox proportional hazards regression models.
At baseline, mean serum 25(OH)D was 31.9 ng/mL in the teriparatide group and 31.5 ng/mL in the risedronate group, and 16.8% and 17.9% of patients, respectively, were 25(OH)D insufficient. At month 6, the mean serum 25(OH)D concentration decreased in teriparatide-treated patients to 24.5 ng/mL (by approximately 23%) but remained relatively constant in risedronate-treated patients (32.2 ng/mL) (p < 0.001). Proportions of 25(OH)D insufficient patients at month 6 were 26.7% and 5.6%, respectively (p < 0.001). The risk reduction with teriparatide versus risedronate for any of the fracture endpoints did not significantly differ between subgroups by 25(OH)D sufficiency status at baseline, with nonsignificant (p > 0.1) treatment-by-25(OH)D interactions in all fracture analyses.
Serum 25(OH)D concentration decreases during teriparatide treatment. Fracture risk reduction with teriparatide versus risedronate did not significantly differ between the two groups of patients defined by baseline 25(OH)D.
ClinicalTrials.gov Identifier: NCT01709110
EudraCT Number: 2012-000123-41
KeywordsTeriparatide Fractures Postmenopausal osteoporosis 25-Hydroxy-vitamin D Subgroup analysis Bisphosphonates
We are indebted to Anja Gentzel-Jorczyk (Clinical Trial Coordinator), and Estrella Crespo and Laura Briones (Data Management) for their contribution to the study, to Ansgar Dressler and Bhawna Basin from Trilogy Writing and Consulting for editorial assistance, to the members of the investigational teams at the study centers, and to the women who participated in the study.
This VERO clinical trial was funded by Lilly.
Compliance with ethical standards
Conflicts of interest
Salvatore Minisola: Speaker and/or consultant fees from: Abiogen, Amgen, DiaSorin, Lilly, Italfarmaco, Fujii, MSD, Takeda. Fernando Marin: Lilly Employee. David L. Kendler: Honoraria, research grants, and/or consultant fees from: Amgen, Lilly, AstraZeneca, Astellas, UCB. Piet Geusens: Research support, consultant and/or speaker fees from: Pfizer, Abbott, Lilly, Amgen, MSD, Roche, UCB, BMS, Novartis. Cristiano A.F. Zerbini: Research support from Lilly. Luis A. Russo: None. Enrique Casado: Speaker fees from: Amgen, Lilly. Astrid Fahrleitner-Pammer: Speaker fees from: Amgen, Alexion, BMS, Lilly, Fresenius. Jan J. Stepan: None. Eric Lespessailles: Speaker and consultant fees from: Amgen, Expanscience, Lilly, MSD; research grants from Abbvie, Amgen, Lilly, MSD, UCB. Rüdiger Möricke: None. Alicia Bagur: Speaker fees from Lilly and Craveri. Péter Lakatos: None. Pedro López-Romero: Lilly Employee. Jean Jacques Body: Speaker fee from Amgen; research support from Lilly.
All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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