VITamin D and OmegA-3 TriaL: Effects on Bone Structure and Architecture

维生素 D 和 OmegA-3 TriaL：对骨骼结构和结构的影响

• 批准号: 9111834
• 负责人: MERYL Susan LEBOFF
• 金额: $ 28.58万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9111834
• 关键词: 25-hydroxyvitamin D; Address; Adult; Affect; Ancillary Study; Architecture; Attention; Biological Markers; Body Composition; Body fat; Body mass index; Bone Density; Bone Resorption; Bone remodeling; Boston; Cardiovascular Diseases; Center for Translational Science Activities; Characteristics; Cholecalciferol; Clinical; Clinical Research; Clinical Sciences; Clinical Trials; Cohort Studies; Collagen Type I; Data; Deterioration; Distal; Dose; Elderly; Enrollment; Equilibrium; Fatty Acids; Fatty acid glycerol esters; Finite Element Analysis; Forearm; Fracture; Funding; Gender; Geometry; Goals; Health; Health Benefit; Height; High Prevalence; High Resolution Computed Tomography; Hip Fractures; Hip region structure; Image; Imaging Techniques; Institute of Medicine (U.S.); Knowledge; Limb structure; Literature; Malignant Neoplasms; Marines; Measurement; Measures; Medical; Obesity; Observational Study; Omega-3 Fatty Acids; Osteocalcin; Osteogenesis; Osteoporosis; Outcome; Participant; Patients; Peripheral; Placebo Control; Placebos; Prevalence; Prevention trial; Primary Prevention; Public Health; Race; Radial; Randomized; Randomized Clinical Trials; Recommendation; Recommended Dietary Allowance; Recruitment Activity; Reporting; Research Priority; Resolution; Resources; Roentgen Rays; Role; Safety; Serum; Skin Pigmentation; Structure; Supplementation; Testing; Thick; Tissues; United States; United States National Institutes of Health; Vertebral column; Visit; Vitamin D; Vitamin D supplementation; Woman; X-Ray Computed Tomography; age related; aged; bone; bone health; bone imaging; bone loss; bone mass; bone strength; bone turnover; cohort; cost effective; design; double-blind placebo controlled trial; efficacy testing; improved; indexing; insight; men; middle age; prevent; protective effect; skeletal; tibia

DESCRIPTION (provided by applicant): There is a high prevalence of inadequate vitamin D levels in the United States. Despite enthusiasm for the use of vitamin D for bone health, there are limited data on the effects of high-dose vitamin D supplements vs. placebo on bone health and body composition outcomes. Previous data support a positive relationship between 25-hydroxyvitamin D [25(OH) D] levels and bone mineral density (BMD). However, results from clinical trials that test vitamin D supplementation alone on areal BMD (aBMD) are sparse and inconsistent, and it is not known whether vitamin D can prevent or reverse the structural deterioration characteristic of osteoporosis. Recent advances in bone imaging make it possible to assess volumetric BMD (vBMD), structure, and micro- architecture non-invasively with high-resolution peripheral computed tomography (HR-pQCT). In addition, observational studies show an inverse relationship between 25(OH) D levels and body mass index (BMI). Since vitamin D is stored in fat, new dual X-ray absorptiometry (DXA) measures of adiposity can advance understanding of this relationship and determine whether or not supplemental vitamin D has effects on body composition. We propose an ancillary study to the NIH-sponsored, Vitamin D and OmegA-3 Trial (VITAL) (U01 CA138962), an ongoing, randomized, double-blind, placebo-controlled trial of vitamin D3 (cholecalciferol, 2000 IU/d) and/or marine omega-3 fatty acids (1 gm/d) in 20,000 men and women, to test the effects of vitamin D3 on BMD, geometry, architecture, and body composition. In a sub-cohort of 600 participants recruited from the NIH-sponsored Clinical and Translational Science Center (CTSC) in Boston, we seek to test the following hypotheses, with measures at baseline and year 2: Aim 1: High-dose vitamin D3 will (a) produce small increases in aBMD at the spine, hip, forearm and total body, as assessed by DXA and (b) improve balance of bone remodeling through decreases in bone turnover; Aim 2: High-dose vitamin D3 will improve: vBMD and bone structure and architecture at the distal radius and tibia, as assessed by HR-pQCT and bone strength estimates; Aim 3: High-dose vitamin D3 will result in lower (a) total body fat and fat mass index (FMI-fat mass/height2) and/or b) regional fat measures, as assessed by DXA. For each Aim, we will determine whether effects vary with (a) baseline 25(OH) D levels, (b) gender, (c) race/skin pigmentation, and (d) BMI or FMI. We will also define how the 25(OH) D levels corresponding to high-dose vitamin D supplementation affects these bone health and body composition outcomes. In order to complete pre-randomization testing in this sub-cohort, it is critical that this ancillary study be undertaken during the CTSC baseline visits, which begin December, 2011 and extend to early 2013. The proposed studies will provide positive or informative negative results about effects of vitamin D3 alone on bone health and body composition, and enhance understanding of the skeletal mechanisms through which vitamin D may affect fracture outcomes evaluated in a separate study (AR060574). Findings from this proposal will fill gaps in knowledge and inform clinical and public health recommendations.

描述（由申请人提供）：美国维生素D水平不足的患病率很高。尽管人们热衷于使用维生素D促进骨骼健康，但关于高剂量维生素D补充剂与安慰剂对骨骼健康和身体组成结果的影响的数据有限。以前的数据支持25-羟基维生素D [25（OH）D]水平和骨密度（BMD）之间的正相关关系。然而，来自单独测试维生素D补充剂对区域BMD（aBMD）的临床试验的结果是稀疏和不一致的，并且不知道维生素D是否可以预防或逆转骨质疏松症的结构恶化特征。骨成像的最新进展使得可以使用高分辨率外周计算机断层扫描（HR-pQCT）无创地评估体积BMD（vBMD）、结构和微结构。此外，观察性研究显示25（OH）D水平与体重指数（BMI）呈负相关。由于维生素D储存在脂肪中，新的双重X射线吸收法（DXA）测量肥胖可以促进对这种关系的理解，并确定补充维生素D是否对身体成分有影响。我们建议对NIH赞助的维生素D和OmegA-3试验（VITAL）进行辅助研究（U 01 CA 138962），一项正在进行的维生素D3随机、双盲、安慰剂对照试验（胆钙化醇，2000 IU/d）和/或海洋ω-3脂肪酸（1 gm/d）在20，000名男性和女性中，以测试维生素D3对BMD，几何形状，结构，和身体组成。在从波士顿NIH赞助的临床和转化科学中心（CTSC）招募的600名参与者的子队列中，我们试图测试以下假设，并在基线和第2年进行测量：目标1：高剂量的维生素D3将（a）在脊柱、臀部、前臂和全身产生aBMD的小幅增加，如通过DXA评估的，和（B）通过降低骨转换来改善骨重建的平衡;目标2：高剂量维生素D3将改善：如通过HR-pQCT和骨强度估计评估的，桡骨远端和胫骨处的vBMD和骨结构和架构;目标3：高剂量的维生素D3将导致较低的（a）总身体脂肪和脂肪质量指数（FMI-fat mass/height 2）和/或 B）通过DXA评估的区域脂肪测量。对于每个目标，我们将确定效应是否随（a）基线25（OH）D水平、（B）性别、（c）种族/皮肤色素沉着和（d）BMI或FMI而变化。我们还将定义与高剂量维生素D补充剂相对应的25（OH）D水平如何影响这些骨骼健康和身体组成结果。为了在该子队列中完成随机化前检测，在CTSC基线访视期间（从2011年12月开始至2013年初）进行该辅助研究至关重要。拟议的研究将提供关于维生素D3单独对骨骼健康和身体组成影响的积极或信息性负面结果，并加强对维生素D可能影响骨折结局的骨骼机制的理解，该机制在单独的研究中进行了评价（AR 060574）。该提案的发现将填补知识空白，并为临床和公共卫生建议提供信息。