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水平不足的发生率很高。尽管人们热衷于使用维生素D来促进骨骼健康，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]水平与骨密度（BMD）呈正相关。然而，仅测试维生素D补充对面积骨密度（aBMD）影响的临床试验结果很少且不一致，而且尚不清楚维生素D是否可以预防或逆转骨质疏松症特征的结构恶化。骨成像的最新进展使得利用高分辨率周围计算机断层扫描（HR-pQCT）无创评估体积骨密度（vBMD）、结构和微结构成为可能。此外，观察性研究表明25(OH) D水平与身体质量指数（BMI）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。我们建议对美国国立卫生研究院赞助的维生素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、随机的、双盲的、安慰剂对照的试验，在20000名男性和女性中进行维生素D3（胆钙化醇，2000 IU/ 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、结构和身体成分的影响。在波士顿美国国立卫生研究院赞助的临床和转化科学中心（CTSC）招募的600名参与者的亚队列中，我们试图通过基线和第二年的测量来测试以下假设：目标1：高剂量维生素D3将(a)产生脊柱，髋关节，前臂和全身的aBMD的小幅增加，正如DXA评估的那样；(b)通过减少骨转换改善骨重塑的平衡；目标2：通过HR-pQCT和骨强度评估，高剂量维生素D3将改善：vBMD和桡骨远端和胫骨的骨结构和建筑；目标3：高剂量维生素D3会降低(a)总脂肪和脂肪质量指数（fmi -脂肪质量/高度2）和/或

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.