Vitamin D and Omega-3 Fatty Acids(VITAL Trial): Effects on Fractures

描述（由申请人提供）：骨质疏松性骨折是与维生素D水平低相关的主要公共卫生问题。以前的数据强烈表明，维生素D = 700 IU/天的剂量减少骨折和可能的福尔斯。基础和小型临床试验表明，ω-3脂肪酸也可能对骨骼有益，但对骨折的影响尚不清楚。在一般人群中进行高剂量维生素D和/或ω-3脂肪酸的大型一级预防试验（即，疾病风险（疾病风险）。我们建议对VITAL研究进行一项辅助研究，VITAL研究是一项关于维生素D的大型、随机、双盲、安慰剂对照试验。（维生素D3 [胆钙化醇]形式）和/或海洋ω-3脂肪酸（二十碳五烯酸[EPA] +二十二碳六烯酸[DHA]）补充剂，以提高知识和测试维生素D3的影响（2000 IU/d）和/或鱼油（EPA+DHA，1 g/d），用于骨折、骨丢失、福尔斯和虚弱的一级预防。人们对补充维生素D以支持骨骼健康和使用鱼油（也可能对骨骼产生影响）的热情日益高涨，这强调了及时启动这项辅助研究以及新资助的VITAL母研究（U 01 CA 138962）的迫切需要。拟议的辅助研究将包括20 000名男女（分别> 65岁和60岁）和来自波士顿、芝加哥、休斯顿和旧金山弗朗西斯科的临床和转化科学中心（CTSC）的700名参与者的该试验的子队列，以严格检验这些假设：主要目的：在VITAL队列中，维生素D3和/或EPA+DHA是否会减少a）总骨折和B）髋关节或非椎骨骨折的发生率？次要目标：在CTSC子队列中，维生素D3和/或EPA+DHA是否会减少脊柱、髋关节和全身的骨丢失，如在基线和第2年通过双X射线吸收测定法评估的，效果是否随（a）这些营养素的基线和随访血液水平、（B）性别、（c）种族/皮肤色素沉着和（d）体重指数而变化？三级目标：在VITAL队列中，维生素D3和/或EPA+DHA补充剂是否会a）减少年度问卷评估的福尔斯风险，以及B）减少基于问卷的虚弱指数确定的虚弱？基线和随访血液采集将按季节逐月匹配，以防止维生素D水平的季节性偏倚。为了在CTSC研究中心完成受试者的随机化前测量，必须与母试验VITAL安慰剂“导入期”平行进行该辅助研究，以获得基线和随访测量值，计划于2010年年中开始。这项时间敏感的辅助研究将严格测试这些营养补充剂在改善骨骼健康方面的作用，并将提供有关维生素D和ω-3脂肪酸对骨折、骨密度、福尔斯和虚弱的影响的积极或信息性无效结果。我们预计，这项辅助研究的结果将为临床实践提供信息，说明高剂量维生素D和/或鱼油是否能减轻与年龄相关的骨折增加的负担，这将带来广泛的公共卫生益处。 公共卫生相关性：骨质疏松性骨折和维生素D水平低是主要的公共卫生问题。一些证据表明，补充维生素D可以降低骨折、骨质流失和福尔斯的风险，但缺乏高剂量维生素D对这些终点的影响。我们建议对大型随机对照临床试验-维生素D和OmegA-3 TriaL（VITAL）-进行一项时间敏感的辅助研究，以评估高剂量维生素D和/或OmegA-3脂肪酸在骨折、骨丢失、福尔斯和虚弱的一级预防中的作用;这项拟议的辅助研究的结果将推动科学发展，并为维生素D和/或ω-3脂肪酸补充剂在骨骼健康和预防骨折中的作用的临床实践提供信息。

DESCRIPTION (provided by applicant): Osteoporotic fractures are major public health problems that have been associated with low vitamin D levels. Previous data strongly suggest that doses of vitamin D = 700 IU/day reduce fractures and possibly falls. Basic and small clinical trials suggest that omega-3 fatty acids may also have beneficial skeletal effects, but effects on fractures are not known. Large primary prevention trials with high daily doses of vitamin D and/or omega-3 fatty acids in general populations (i.e., unselected for disease risk) are lacking. We propose an ancillary study to the VITAL study, a large, randomized, double-blind, placebo-controlled trial of vitamin D (in the form of vitamin D3 [cholecalciferol]) and/or marine omega-3 fatty acid (eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA]) supplements, to advance knowledge and test the effects of vitamin D3 (2000 IU/d) and/or fish oil (EPA+DHA, 1g/d) for primary prevention of fractures, bone loss, falls, and frailty. Growing enthusiasm for supplemental vitamin D to support bone health, and use of fish oil, which may also have skeletal effects, underscores the urgent need for a timely initiation of this ancillary study in conjunction with the newly funded VITAL parent study (U01CA 138962). The proposed ancillary study will include 20,000 women and men (>age 65 and 60, respectively) from the 5-year, NIH-sponsored, parent VITAL trial and a sub-cohort from that trial of 700 participants from Clinical and Translational Science Centers (CTSCs) in Boston, Chicago, Houston, and San Francisco to critically test these hypotheses: Primary Aims: In the VITAL cohort, will vitamin D3 and/or EPA+DHA reduce incident a) total fractures and b) hip or non-vertebral fractures? Secondary Aims: In the CTSC sub-cohort, will vitamin D3 and/or EPA+DHA reduce bone loss of the spine, hip, and total body, as assessed by Dual X-ray Absorptiometry at baseline and year 2 and do effects vary with (a) baseline and follow up blood levels of these nutrients, (b) gender, (c) race/skin pigmentation, and (d) body mass index? Tertiary Aims: In the VITAL cohort, will Vitamin D3 and/or EPA+DHA supplementation a) reduce the risk of falls as assessed by annual questionnaires and b) reduce frailty as determined by the questionnaire- based frailty index? Baseline and follow-up blood collections will be matched for season by month to prevent seasonal bias for vitamin D levels. In order to complete pre-randomization measurements among participants in the CTSC sites, it is essential that this ancillary study be undertaken in parallel to the parent VITAL trial placebo "run-in" to get baseline and follow-up measurements, which is scheduled to begin in mid-2010. This time-sensitive ancillary study will rigorously test the role of these nutritional supplements in improving skeletal health and will provide positive or informative null results on the effects of vitamin D and omega-3 fatty acids on fractures, bone density, falls, and frailty. We expect that findings from this ancillary study will inform clinical practice on whether high daily dose vitamin D and/or fish oil reduces the burden of age-related increases in fractures, which would result in widespread public health benefits. PUBLIC HEALTH RELEVANCE: Osteoporotic fractures and low vitamin D levels are major public health concerns. Several lines of evidence suggest that supplemental vitamin D may reduce the risk of fractures, bone loss, and falls, but the effects of high-dose vitamin D on these endpoints are lacking. We propose to conduct a time-sensitive, ancillary study to the large, randomized, controlled clinical trial - the VITamin D and OmegA-3 TriaL (VITAL) - to evaluate the role of high dose vitamin D and/or omega-3 fatty acids in the primary prevention of fractures, bone loss, falls, and also frailty; findings from this proposed ancillary study will advance science and inform clinical practice on the role(s) of vitamin D and/or omega-3 fatty acid supplements in bone health and fracture prevention.