维生素 D 治疗反应的临床和生物标志物修饰物：动脉粥样硬化的多民族研究。
Clinical and biomarker modifiers of vitamin D treatment response: the Multi-Ethnic Study of Atherosclerosis.
机构信息
Division of Nephrology and Kidney Research Institute, Department of Medicine, University of Washington, Seattle, WA, USA.
Department of Biostatistics, University of Washington, Seattle, WA, USA.
出版信息
Am J Clin Nutr. 2022 Mar 4;115(3):914-924. doi: 10.1093/ajcn/nqab390.
BACKGROUND
Different 25-hydroxyvitamin D [25(OH)D] thresholds for treatment with vitamin D supplementation have been suggested and are derived almost exclusively from observational studies. Whether other characteristics, including race/ethnicity, BMI, and estimated glomerular filtration rate (eGFR), should also influence the threshold for treatment is unknown.
OBJECTIVES
The aim was to identify clinical and biomarker characteristics that modify the response to vitamin D supplementation.
METHODS
A total of 666 older adults in the Multi-Ethnic Study of Atherosclerosis (MESA) were randomly assigned to 16 wk of oral vitamin D3 (2000 IU/d; n = 499) or placebo (n = 167). Primary outcomes were changes in serum parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations from baseline to 16 wk.
RESULTS
Among 666 participants randomly assigned (mean age: 72 y; 53% female; 66% racial/ethnic minority), 611 (92%) completed the study. The mean (SD) change in PTH was -3 (16) pg/mL with vitamin D3 compared with 2 (18) pg/mL with placebo (estimated mean difference: -5; 95% CI: -8, -2 pg/mL). Within the vitamin D3 group, lower baseline 25-hydroxyvitamin D [25(OH)D] was associated with a larger decline in PTH in a nonlinear fashion. With baseline 25(OH)D ≥30 ng/mL as the reference, 25(OH)D <20 ng/mL was associated with a larger decline in PTH with vitamin D3 supplementation (-10; 95% CI: -15, -6 pg/mL), whereas 25(OH)D of 20-30 ng/mL was not (-2; 95% CI: -6, 1 pg/mL). A segmented threshold model identified a baseline 25(OH)D concentration of 21 (95% CI: 13, 31) ng/mL as an inflection point for difference in change in PTH. Race/ethnicity, BMI, and eGFR did not modify vitamin D treatment response. There was no significant change in 1,25(OH)2D in either treatment group.
CONCLUSIONS
Of characteristics most commonly associated with vitamin D metabolism, only baseline 25(OH)D <20 ng/mL modified the PTH response to vitamin D supplementation, providing support from a clinical trial to use this threshold to define insufficiency. This trial was registered at clinicaltrials.gov as NCT02925195.
背景
不同的 25-羟维生素 D [25(OH)D] 治疗阈值已被提出，并且几乎完全来自观察性研究。其他特征，包括种族/民族、BMI 和估计的肾小球滤过率 (eGFR)，是否也应该影响治疗阈值尚不清楚。
目的
本研究旨在确定能改变维生素 D 补充治疗反应的临床和生物标志物特征。
方法
共纳入 666 名来自多民族动脉粥样硬化研究（MESA）的老年人，他们被随机分配至口服维生素 D3（2000 IU/d；n=499）或安慰剂（n=167）组，共 16 周。主要结局为血清甲状旁腺激素（PTH）和 1,25-二羟维生素 D [1,25(OH)2D] 浓度从基线到 16 周的变化。
结果
在 666 名被随机分配的参与者（平均年龄：72 岁；53%为女性；66%为少数民族）中，611 名（92%）完成了研究。与安慰剂组相比，维生素 D3 组的 PTH 下降幅度更大，为 -3（16）pg/mL 比 2（18）pg/mL（估计平均差值：-5；95%CI：-8，-2 pg/mL）。在维生素 D3 组内，25-羟维生素 D [25(OH)D] 基线值越低，PTH 下降幅度越大，呈非线性趋势。以基线 25(OH)D≥30 ng/mL 为参考，25(OH)D<20 ng/mL 与维生素 D3 补充剂治疗时 PTH 下降幅度更大（-10；95%CI：-15，-6 pg/mL），而 25(OH)D 为 20-30 ng/mL 时则没有（-2；95%CI：-6，1 pg/mL）。分段阈值模型确定 25(OH)D 基线浓度为 21（95%CI：13，31）ng/mL 为 PTH 变化差异的拐点。种族/民族、BMI 和 eGFR 未改变维生素 D 治疗反应。两组患者的 1,25(OH)2D 均无明显变化。
结论
在与维生素 D 代谢最相关的特征中，只有基线 25(OH)D<20 ng/mL 改变了维生素 D 补充对 PTH 的反应，这为使用该阈值来定义不足提供了临床试验依据。本研究在 clinicaltrials.gov 上注册，编号为 NCT02925195。
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