卡尔加里维生素D研究中维生素D代谢组的测量：维生素D代谢产物与骨丢失的关系

IF 5.1 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Journal of Bone and Mineral Research Pub Date : 2023-07-06 DOI:10.1002/jbmr.4876

Lauren A. Burt, Martin Kaufmann, Marianne S. Rose, Glenville Jones, Emma O. Billington, Steven K. Boyd, David A. Hanley

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引用次数: 0

摘要

在一项为期36个月的随机对照试验中，研究了高剂量维生素D3对桡骨和胫骨总骨密度（TtBMD）的影响，通过高分辨率外周定量断层扫描（HR-pQCT）测量，参与者（311名55-70岁的健康男性和女性双能X射线吸收仪T型芯>；−2.5，无维生素D缺乏）随机接受400 IU（N = 109），4000 IU（N = 100），或10000 IU（N = 102）。参与者在基线、6、12、24和36时进行HR-pQCT桡骨和胫骨扫描和血液采样月。这项二次分析通过液相色谱-串联质谱法（LC-MS/MS）检测了维生素D剂量对维生素D代谢组血浆测量的影响，探讨了观察到的TtBMD下降是否与四种关键代谢产物[25-（OH）D3；24,25-（OH）2D3；1,25-（OH2D3；和1,24,25-（OH）3D3]的变化有关。维生素D代谢产物峰值与36岁以上TtBMD变化的关系在控制性别的情况下，采用线性回归法对月数进行评估。维生素D剂量的增加与25-（OH）D3、24,25-（OH）2D3和1,24,25-（OH）3D3的显著增加有关，但未观察到血浆1,25-（OH2D3的剂量相关变化。半径TtBMD和1,24,25-（OH）3D3存在显著的负斜率（−0.05，95%置信区间[CI]−0.08，−0.03，p <； 0.001）。对于25-（OH）D3，TtBMD与性别之间存在显著的相互作用（女性：−0.01，95%CI−0.12，−0.07；男性：−0.04，95%CI−0.06，−0.01，p = 0.001）和24,25-（OH）2D3（雌性：−0.75，95%CI−0.98，−0.52；雄性：−0.35，95%CI–0.59，−0.11，p <； 0.001）。对于胫骨，25-（OH）D3存在显著的负斜率（-0.03，95%CI−0.05，−0.01，p <； 0.001），24,25-（OH）2D3（−0.30，95%CI−0.44，−0.16，p <； 0.001）和1,24,25-（OH）3D3（−0.03，95%CI−0.05，−0.01，p = 0.01）。这些结果表明，除1,25-（OH）2D3外的维生素D代谢产物可能是卡尔加里维生素D研究中发现的骨丢失的原因。尽管血浆1,25-（OH）2D3没有随着维生素D剂量的变化而变化，但对1,24,25-（OH）3D3的快速分解代谢可能阻止了血浆1,25-。©2023作者。由Wiley Periodicals LLC代表美国骨与矿物研究学会（ASBMR）出版的《骨与矿产研究杂志》。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Measurements of the Vitamin D Metabolome in the Calgary Vitamin D Study: Relationship of Vitamin D Metabolites to Bone Loss

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Measurements of the Vitamin D Metabolome in the Calgary Vitamin D Study: Relationship of Vitamin D Metabolites to Bone Loss

In a 36-month randomized controlled trial examining the effect of high-dose vitamin D₃ on radial and tibial total bone mineral density (TtBMD), measured by high-resolution peripheral quantitative tomography (HR-pQCT), participants (311 healthy males and females aged 55–70 years with dual-energy X-ray absorptiometry T-scores > −2.5 without vitamin D deficiency) were randomized to receive 400 IU (N = 109), 4000 IU (N = 100), or 10,000 IU (N = 102) daily. Participants had HR-pQCT radius and tibia scans and blood sampling at baseline, 6, 12, 24, and 36 months. This secondary analysis examined the effect of vitamin D dose on plasma measurements of the vitamin D metabolome by liquid chromatography–tandem mass spectrometry (LC-MS/MS), exploring whether the observed decline in TtBMD was associated with changes in four key metabolites [25-(OH)D₃; 24,25-(OH)₂D₃; 1,25-(OH)₂D₃; and 1,24,25-(OH)₃D₃]. The relationship between peak values in vitamin D metabolites and changes in TtBMD over 36 months was assessed using linear regression, controlling for sex. Increasing vitamin D dose was associated with a marked increase in 25-(OH)D₃, 24,25-(OH)₂D₃ and 1,24,25-(OH)₃D₃, but no dose-related change in plasma 1,25-(OH)₂D₃ was observed. There was a significant negative slope for radius TtBMD and 1,24,25-(OH)₃D₃ (−0.05, 95% confidence interval [CI] −0.08, −0.03, p < 0.001) after controlling for sex. A significant interaction between TtBMD and sex was seen for 25-(OH)D₃ (female: −0.01, 95% CI −0.12, −0.07; male: −0.04, 95% CI −0.06, −0.01, p = 0.001) and 24,25-(OH)₂D₃ (female: −0.75, 95% CI −0.98, −0.52; male: −0.35, 95% CI −0.59, −0.11, p < 0.001). For the tibia there was a significant negative slope for 25-(OH)D₃ (−0.03, 95% CI −0.05, −0.01, p < 0.001), 24,25-(OH)₂D₃ (−0.30, 95% CI −0.44, −0.16, p < 0.001), and 1,24,25-(OH)₃D₃ (−0.03, 95% CI −0.05, −0.01, p = 0.01) after controlling for sex. These results suggest vitamin D metabolites other than 1,25-(OH)₂D₃ may be responsible for the bone loss seen in the Calgary Vitamin D Study. Although plasma 1,25-(OH)₂D₃ did not change with vitamin D dose, it is possible rapid catabolism to 1,24,25-(OH)₃D₃ prevented the detection of a dose-related rise in plasma 1,25-(OH)₂D₃. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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来源期刊

Journal of Bone and Mineral Research 医学-内分泌学与代谢

CiteScore

11.30

自引率

6.50%

发文量

257

审稿时长

2 months

期刊介绍： The Journal of Bone and Mineral Research (JBMR) publishes highly impactful original manuscripts, reviews, and special articles on basic, translational and clinical investigations relevant to the musculoskeletal system and mineral metabolism. Specifically, the journal is interested in original research on the biology and physiology of skeletal tissues, interdisciplinary research spanning the musculoskeletal and other systems, including but not limited to immunology, hematology, energy metabolism, cancer biology, and neurology, and systems biology topics using large scale “-omics” approaches. The journal welcomes clinical research on the pathophysiology, treatment and prevention of osteoporosis and fractures, as well as sarcopenia, disorders of bone and mineral metabolism, and rare or genetically determined bone diseases.