特立帕肽与利塞膦酸钠 VERTO 临床试验中血清 25-羟维生素 D 与骨折风险的关系。

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

机构信息

Department of Internal Medicine and Medical Disciplines, Sapienza Rome University, Viale del Policlinico 151, 00161, Rome, Italy.

Lilly Research Center Europe, Madrid, Spain.

出版信息

Arch Osteoporos. 2019 Jan 18;14(1):10. doi: 10.1007/s11657-019-0561-x.

DOI:10.1007/s11657-019-0561-x

PMID:30659410

Abstract

PURPOSE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

TRIAL REGISTRATION

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

摘要

目的

本研究利用为期 2 年、随机、双盲、VERO 试验的数据，考察了患者血清 25-羟维生素 D（25[OH]D）浓度随时间的变化情况，并探讨了特立帕肽相对于利塞膦酸钠降低骨折风险的效果是否因基线 25（OH）D 充足程度类别而异。

方法

患有骨质疏松症的绝经后女性接受了每日皮下注射特立帕肽 20μg 或每周口服利塞膦酸钠 35mg 治疗，同时给予 500-1000mg 元素钙和 400-800IU/天的维生素 D 补充剂。骨折终点通过预先设定的 25（OH）D 不足和充足患者亚组进行分析。通过逻辑和 Cox 比例风险回归模型研究了治疗对骨折的影响是否存在异质性。

结果

在基线时，特立帕肽组的平均血清 25（OH）D 为 31.9ng/mL，利塞膦酸钠组为 31.5ng/mL，分别有 16.8%和 17.9%的患者 25（OH）D 不足。在 6 个月时，特立帕肽治疗患者的血清 25（OH）D 浓度下降至 24.5ng/mL（约 23%），而利塞膦酸钠治疗患者的血清 25（OH）D 浓度相对保持不变（32.2ng/mL）（p<0.001）。6 个月时 25（OH）D 不足患者的比例分别为 26.7%和 5.6%（p<0.001）。特立帕肽与利塞膦酸钠治疗的任何骨折终点风险降低在基线时 25（OH）D 充足状态的亚组间均无显著差异（p>0.1），所有骨折分析中均未观察到治疗与 25（OH）D 之间有显著的交互作用（p>0.1）。