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VITamin D and OmegA-3 TriaL (VITAL): Interrelationship of Vitamin D and Vitamin K on Bone

维生素 D 和 OmegA-3 TriaL (VITAL)：维生素 D 和维生素 K 对骨骼的相互关系

基本信息

批准号：
10219961
负责人：
MERYL Susan LEBOFF
金额：
$ 65.68万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10219961
关键词：
Affect African American American Ancillary Study Architecture Attenuated Biological Markers Blood specimen Body mass index Bone Density Bone Diseases Bone Matrix Bone structure Calcium Cardiovascular Diseases Cholecalciferol Collection Creatinine Deposition Deterioration Dose Dual-Energy X-Ray Absorptiometry Elderly Ethnic Origin Fasting Femoral Fractures Fish Oils Fracture Goals Grant Guidelines High Prevalence Hip Fractures Intake Intestines Kidney Kidney Calculi Knowledge Malignant Neoplasms Measures Medical Records Nephrolithiasis Norway Observational Study Omega-3 Fatty Acids Osteocalcin Osteoporosis Outcome PTH gene Parents Participant Peripheral Placebos Play Primary Cancer Prevention Production Proteins Public Health Questionnaires Race Randomized Randomized Controlled Trials Recommendation Resources Risk Risk Factors Rodent Model Role Serum Spottings Structure Supplementation Testing Tissues Toxic effect Trabecular Bone Score United States National Institutes of Health Urine Vitamin D Vitamin D Deficiency Vitamin D supplementation Vitamin K Vitamin K 1 Woman X-Ray Computed Tomography adjudicate adjudication age group aged bone bone health bone loss bone mass bone turnover calcification calcium absorption calcium excretion carboxylate carboxylation clinical care cohort cost cost efficient design dietary follow-up fracture risk fragility fracture high risk imaging study improved innovation insight matrix Gla protein men older men older women protein K protein function radiological imaging recruit sex soft tissue systematic review

项目摘要

ABSTRACT Osteoporosis is the most common bone disease; 53.6 million Americans have a reduced bone mass, which increases their risk of fragility fractures. In addition to the high prevalence of vitamin D deficiency, recent studies show that approximately 60% of older men and 40% of older women have inadequate vitamin K intakes. Growing evidence indicates that there are important interrelationships between vitamin D and vitamin K on bone. Vitamin D increases intestinal calcium absorption and stimulates production of two proteins, osteocalcin and matrix Gla protein. Vitamin K plays an essential role in activating these proteins so that osteocalcin incorporates calcium in bone and matrix Gla protein inhibits calcification in soft tissues, including the kidney. Both vitamins D and K are important for optimal function of these proteins. Although vitamin D supplements are widely used to improve bone health, trials of supplemental vitamin D alone in reducing fractures showed inconsistent results. Emerging evidence indicates that supplemental D in the context of low vitamin K status is less effective on bone health measures. Therefore, low vitamin K status may account for some of the inconsistencies of trials testing vitamin D and bone health and may contribute to toxicities attributed to high-dose vitamin D such as kidney stones. No previous randomized controlled trials have been adequately powered to test effects of vitamin K status on fracture risk or the interaction of vitamin K status with high-dose, supplemental vitamin D on bone. To fill knowledge gaps, we propose an innovative, ancillary study to the large, NIH-sponsored, VITamin D and OmegA-3 TriaL (VITAL). VITAL is testing effects of supplemental vitamin D3 (cholecalciferol, 2000 IU/d), and/or omega-3 fatty acids (fish oil, 1 g/d) in the primary prevention of cancer and cardiovascular disease in 25,871 U.S. men (aged ≥50) and women (aged ≥55), including 5,106 African Americans. In this competitive renewal application of “VITAL: Effects on Bone Structure and Architecture,” we will determine whether low vitamin K status, assessed by 3 sensitive biomarkers, modifies effects of supplemental vitamin D on fractures, bone mineral density (BMD) and structure, and secondarily on increases in urine calcium excretion, a risk factor for low BMD and kidney stones. During the first cycle of this grant, we surpassed recruitment goals and collected baseline and 2-yr post-randomization imaging studies for bone density, structure and architecture that will be used in the proposed studies (n=771). In addition, other key VITAL resources will be leveraged including: 16,953 baseline and 6,000 follow-up blood samples; measures of vitamin D, calcium, creatinine and parathyroid hormone; and adjudicated fractures and kidney stones. This proposal provides a unique opportunity to clarify in the largest study of supplemental vitamin D, the interdependencies of vitamins D and K and their roles on fractures, bone health measures, and urine calcium excretion. Findings from the proposed ancillary study will be critical to the interpretation of on-going vitamin D trials and provide new insights to advance clinical care and public health recommendations.

抽象的骨质疏松症是最常见的骨病； 5360 万美国人骨量减少，增加了脆性骨折的风险。除了维生素 D 缺乏症的高患病率之外，最近研究表明，大约 60% 的老年男性和 40% 的老年女性维生素 K 不足摄入量。越来越多的证据表明维生素 D 和维生素之间存在重要的相互关系骨头上的K。维生素 D 增加肠道钙吸收并刺激两种蛋白质的产生，骨钙素和基质 Gla 蛋白。维生素 K 在激活这些蛋白质方面发挥着重要作用，因此骨钙素将钙结合到骨骼和基质中 Gla 蛋白抑制软组织的钙化，包括肾脏。维生素 D 和 K 对于这些蛋白质的最佳功能都很重要。虽然维生素D 补充剂被广泛用于改善骨骼健康，单独补充维生素 D 的试验可减少骨骼健康骨折结果不一致。新出现的证据表明，在低水平的情况下补充 D 维生素 K 状态对骨骼健康措施的影响较小。因此，维生素 K 水平低可能是导致测试维生素 D 和骨骼健康的试验存在一些不一致之处，可能会导致毒性归因于高剂量维生素 D，如肾结石。之前没有进行过随机对照试验足以测试维生素 K 状态对骨折风险的影响或维生素 K 状态与骨折风险的相互作用高剂量补充骨骼维生素 D。为了填补知识空白，我们提出了一项创新的辅助研究 NIH 赞助的大型维生素 D 和 OmegA-3 TriaL (VITAL)。 VITAL 正在测试补充品的效果维生素 D3（胆钙化醇，2000 IU/天）和/或 omega-3 脂肪酸（鱼油，1 g/天）用于一级预防 25,871 名美国男性（年龄≥50 岁）和女性（年龄≥55 岁）患有癌症和心血管疾病，其中 5,106 名非裔美国人。在“VITAL：对骨结构和骨结构的影响”的竞争性更新应用中架构”，我们将确定通过 3 种敏感生物标志物评估的低维生素 K 状态是否会改变补充维生素 D 对骨折、骨矿物质密度 (BMD) 和结构的影响，其次是对尿钙排泄增加，这是低骨密度和肾结石的危险因素。在本次第一个周期中拨款，我们超越了招募目标，并收集了基线和 2 年随机化后成像研究将在拟议研究中使用的骨密度、结构和架构 (n=771)。此外，其他将利用关键的 VITAL 资源，包括： 16,953 份基线和 6,000 份后续血液样本；维生素 D、钙、肌酐和甲状旁腺激素的测量；并判定骨折和肾脏石头。该提案提供了一个独特的机会，可以在最大规模的补充维生素 D 研究中阐明，维生素 D 和 K 的相互依赖性及其对骨折、骨骼健康指标和尿液的作用钙的排泄。拟议的辅助研究的结果对于解释正在进行的研究至关重要维生素 D 试验并为推进临床护理和公共卫生建议提供新见解。