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: 8372176
• 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 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8372176
• 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; Glosso-Sterandryl; 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; 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; 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. PUBLIC HEALTH RELEVANCE: The purported health benefits of vitamin D are receiving wide attention in the medical literature and the popular press. While some data support a benefit of vitamin D on fracture reduction, there is no information on the effects of high-dose vitamin D on bone structure and architecture and the effects of adiposity on these relationships. Findings from these clinical studies including advanced imaging techniques will elucidate the role of vitamin D on bone mass, architecture and body composition in men and women enrolled in the VITAL study.

描述（由申请人提供）：在美国，维生素 D 水平不足的现象非常普遍。尽管人们热衷于使用维生素 D 来促进骨骼健康，但有关高剂量维生素 D 补充剂与安慰剂对骨骼健康和身体成分结果的影响的数据有限。先前的数据支持 25-羟基维生素 D [25(OH) D] 水平与骨矿物质密度 (BMD) 之间存在正相关关系。然而，仅测试补充维生素 D 对面积 BMD (aBMD) 的临床试验结果很少且不一致，并且尚不清楚维生素 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利用高分辨率外周计算机断层扫描 (HR-pQCT) 非侵入性地评估体积 BMD (vBMD)、结构和微体系结构成为可能。此外，观察性研究表明 25(OH) D 水平与体重指数 (BMI) 之间呈反比关系。由于维生素 D 储存在脂肪中，新的双 X 射线吸收测定法 (DXA) 测量肥胖症的方法可以加深对这种关系的理解，并确定补充维生素 D 是否对身体成分产生影响。我们建议对 NIH 资助的维生素 D 和 OmegA-3 试验 (VITAL) (U01 CA138962) 进行一项辅助研究，该试验是一项正在进行的随机、双盲、安慰剂对照试验，对 20,000 名男性和女性进行维生素 D3（胆钙化醇，2000 IU/天）和/或海洋 omega-3 脂肪酸（1 克/天），以测试效果 维生素 D3 对 BMD、几何形状、结构和身体成分的影响。在从 NIH 资助的波士顿临床和转化科学中心 (CTSC) 招募的 600 名参与者组成的小组中，我们试图通过基线和第 2 年的测量来测试以下假设：目标 1：高剂量维生素 D3 将 (a) 通过 DXA 评估，使脊柱、髋部、前臂和全身的 aBMD 小幅增加；(b) 通过 DXA 评估，改善骨重塑的平衡 骨转换减少；目标 2：高剂量维生素 D3 将改善： vBMD 以及桡骨远端和胫骨的骨结构和架构，通过 HR-pQCT 和骨强度估计进行评估；目标 3：高剂量维生素 D3 将降低 (a) 全身脂肪和脂肪质量指数（FMI-脂肪质量/身高2）和/或 b) 区域脂肪测量，由 DXA 评估。对于每个目标，我们将确定效果是否随 (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 的变化而变化。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成分结果。为了完成该子队列的预随机化测试，这项辅助研究必须在 CTSC 基线访视期间进行，这一过程从 2011 年 12 月开始一直延续到 2013 年初。拟议的研究将提供有关单独使用维生素 D3 对骨骼健康和身体成分的影响的积极或翔实的消极结果，并加深对维生素 D 可能影响骨折结果的骨骼机制的理解（在另一项研究中评估） （AR060574）。该提案的研究结果将填补知识空白并为临床和公共卫生建议提供信息。 公众健康相关性：维生素 D 所谓的健康益处正在受到医学文献和大众媒体的广泛关注。虽然一些数据支持维生素 D 对减少骨折的益处，但没有关于高剂量维生素 D 对骨骼结构和结构的影响以及肥胖对这些关系的影响的信息。这些临床研究的结果（包括先进的成像技术）将阐明维生素 D 对参加 VITAL 研究的男性和女性的骨量、结构和身体成分的作用。