在36个月的RCT检查高剂量维生素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名年龄在55~70岁,DXAT评分>-2.5,无维生素D缺乏的健康男性和女性)随机接受每日400IU(N=109);4,000IU(N=100);10,000IU(N=102).参与者在基线时进行了HR-pQCT半径和胫骨扫描以及血液采样,6、12、24和36个月。该二级分析通过液相色谱-串联质谱法(LC-MS/MS)检查了维生素D剂量对维生素D代谢组血浆测量的影响,探索观察到的TtBMD下降是否与4种关键代谢物[25-(OH)D3;24,25-(OH)2D3;1,25-(OH)2D3;和1,24,25-(OH)3D3]的变化相关。使用线性回归评估了36个月内维生素D代谢物的峰值与TtBMD变化之间的关系,控制性。维生素D剂量的增加与25-(OH)D3的显着增加有关,24,25-(OH)2D3和1,24,25-(OH)3D3,但未观察到血浆1,25-(OH)2D3的剂量相关变化。控制性别后,半径TtBMD和1,24,25-(OH)3D3(-0.05,95CI-0.08,-0.03,p<0.001)存在显着的负斜率。25-(OH)D3(女性:-0.01,95CI-0.12,-0.07;男性:-0.04,95CI-0.06,-0.01,p=0.001)和24,25-(OH)2D3(女性:-0.75,95CI-0.98,-0.52;男性:-0.35,95CI-0.59,-0.11,p<0.001)。对于胫骨,25-(OH)D3(-0.03,95CI-0.05,-0.01,p<0.001)具有显着的负斜率,和24,25-(OH)2D3(-0.30,95CI-0.44,-0.16,p<0.001),和1,24,25-(OH)3D3(-0.03,95CI-0.05,-0.01,p=0.01)。这些结果表明,1,25-(OH)2D3以外的维生素D代谢物可能是卡尔加里维生素D研究中发现的骨丢失的原因。虽然血浆1,25-(OH)2D3没有随维生素D剂量而变化,1,24,25-(OH)3D3的快速分解代谢可能阻止检测到血浆1,25-(OH)2D3的剂量相关升高。本文受版权保护。保留所有权利。
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)2 D3 ; 1,25-(OH)2 D3 ; and 1,24,25-(OH)3 D3 ]. 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)2 D3 and 1,24,25-(OH)3 D3 , but no dose-related change in plasma 1,25-(OH)2 D3 was observed. There was a significant negative slope for radius TtBMD and 1,24,25-(OH)3 D3 (-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)2 D3 (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)2 D3 (-0.30, 95% CI -0.44, -0.16, p < 0.001), and 1,24,25-(OH)3 D3 (-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)2 D3 may be responsible for the bone loss seen in the Calgary Vitamin D
Study. Although plasma 1,25-(OH)2 D3 did not change with vitamin D dose, it is possible rapid catabolism to 1,24,25-(OH)3 D3 prevented the detection of a dose-related rise in plasma 1,25-(OH)2 D3 . © 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).