Serum 25-hydroxy-vitamin D and the risk of fractures in the teriparatide versus risedronate VERO clinical trial.

Abstract

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 20μg or oral weekly risedronate 35mg, with concomitant 500-1000mg of elemental calcium and 400-800IU/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 31.9ng/mL in the teriparatide group and 31.5ng/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 24.5ng/mL (by approximately 23%) but remained relatively constant in risedronate-treated patients (32.2ng/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.