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

描述(由申请人提供)：在美国，维生素D水平不足的情况很普遍。尽管人们热衷于使用维生素D促进骨骼健康，但关于大剂量维生素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。以前的数据支持25-羟基维生素D[25(OH)D]水平与骨密度(BMD)之间的正相关关系。然而，仅测试补充维生素D对面骨密度(ABMD)的临床试验结果稀少且不一致，而且尚不清楚维生素D能否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)无创地评估体积骨密度(VBMD)、结构和微结构成为可能。此外，观察性研究表明，25(OH)D水平与体重指数(BMI)呈负相关。由于维生素D储存在脂肪中，新的肥胖双X射线吸收测量法(DXA)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)(U01 CA138962)进行一项辅助研究，这是一项正在进行的、随机、双盲、安慰剂对照的维生素D3(胆钙素，2000IU/d)和/或海洋omega-3脂肪酸(1 gm/d)的试验，以测试维生素D3对骨密度、几何形状、结构和身体成分的影响。在从波士顿NIH赞助的临床和翻译科学中心(CTSC)招募的600名参与者中，我们试图测试以下假设，并在基线和第二年采取措施：目标1：大剂量维生素D3将(A)通过DXA评估，在脊柱、髋部、前臂和全身产生小幅增加的骨密度，(B)通过减少骨转换来改善骨重建的平衡；目标2：大剂量维生素D3将改善：vBMD以及通过HR-pQCT和骨强度评估评估的桡骨远端和胫骨的骨结构和结构；目标3：大剂量维生素D3将导致(A)总体脂肪和脂肪质量指数(FMI-脂肪质量/身高2)和/或 B)DXA评估的区域FAT措施。对于每个目标，我们将确定影响是否随(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。我们还将定义与大剂量维生素D补充相对应的25(OH)D水平如何影响这些骨骼健康和身体成分结果。为了在这一分群中完成预随机化测试，至关重要的是，这项辅助研究必须在反恐委员会基线访问期间进行，该基线访问从2011年12月开始，一直持续到2013年初。拟议的研究将提供关于维生素D3单独对骨骼健康和身体成分的影响的积极或有益的负面结果，并加强对维生素D可能影响骨折结果的骨骼机制的理解，在另一项研究中进行了评估(AR060574)。这项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。

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.