Supplemental Vitamin D and Functional Outcomes in Early Adolescence

儿童的维生素D摄入量不符合目前美国膳食参考摄入量（DRI）的建议，新出现的证据表明，相当多的儿童，特别是那些皮肤色素沉着较深的儿童，血清25-羟基维生素D [25(OH)D]水平不足。在成人中，根据血清甲状旁腺激素（PTH）浓度、钙吸收和骨折率，血清25(OH)D“SO nmol/L被认为是达到充足的目标。在较年轻的人群中，循环25(OH)D的最佳水平还没有明确的定义，也不知道什么样的功能结果测量是定义这一水平的理想方法。此外，尚不清楚这些要求是否会因种族而异。该项目的具体目的是确定生活在美国北部和南部地区的青春期早期男性（10 - 13岁，n=160）和女性（9 - 12岁，n=160）： 1)口服维生素D补充剂是否以及在多大程度上改变维生素D和骨代谢的中间终点[即血清25(OH)D， PTH和1,25(OHhD，分数钙吸收和骨转换的生化指标]；2)是否种族改变了这些维生素D和骨代谢的中间终点对维生素D补充的反应；3)阐明25(OH)D浓度与血清PTH、1,25(OH)2D和分数钙吸收等变量之间的关系，特别感兴趣的是确定是否存在一个“收益递减”点，即25(OH)D的增加与其他变量的变化越来越小有关。在这项为期12周（冬季）的双盲、随机、安慰剂对照试验中，维生素D3补充剂量为0 IU（安慰剂，n=64）、400 IU[设定为当前美国儿科学会推荐剂量（n=64）]、1,000 IU （n=64）、2,000 IU （n=64）和4,000 IU （n=64）。为了评估对维生素D补充的生化反应是否存在种族差异，这些小组将按种族（白人和黑人）分层。还将获得主观的日晒测量来估计维生素D的皮肤合成。假设补充维生素D 12周后，将观察到维生素D补充与以下反应变量的平衡平均值之间的剂量-反应关系：血清25(OH}D， PTH和1,25 (OHhD)，分数钙吸收和骨转换的生化标志物。我们的第二个假设是，种族会改变这些维生素D和骨代谢的中间终点对口服维生素D剂量增加的反应。这个提议的双站点和多学科项目将解决2006年DRI研究综合研讨会和2007年卫生保健研究和质量证据机构报告中确定的关键研究重点，并将推进我们对基于血清25(OH)D和中间产物的成长儿童维生素D需求的理解skeietai健康的端点。这项研究的发现对旨在改善美国儿童健康的维生素D摄入量建议具有重要的公共卫生意义。

Vitamin D intakes' in children do not meet current US Dietary Reference Intake (DRI) recommendations and emerging evidence suggests that a significant number of children, particularly those with darker skin pigmentation, have inadequate levels of serum 25-hydroxyvitamin D [25(OH)D]. In adults, achieving serum 25(OH)D "SO nmol/L has been suggested as a target for sufficiency based on serum parathyroid hormone (PTH) concentrations, calcium absorption and fracture rates. In younger populations, the optimum level of circulating 25(OH)D has not been clearly defined, nor is it known what functional outcome measures are ideal for defining this level. Moreover, it is unknown if these requirements would differ by race. The specific aims of this project are to determine in early pubertal males (aged 10 to 13 years; n=160) and females (aged 9 to 12 years; n=160) living in northern and southern regions of the US: 1) whether, and to what degree, oral vitamin D supplementation alters intermediate endpoints of vitamin D and bone metabolism [i.e., serum 25(OH)D, PTH and 1,25(OHhD, fractional calcium absorption, and biochemical markers of bone turnover]; 2) if race modifies the responses of these intermediate endpoints of vitamin D and bone metabolism to vitamin D supplementation; and 3) to elucidate the relationships between 25(OH}D concentration and each of the variables serum PTH, 1,25(OH)2D and fractional calcium absorption, with particular interest in determining whether there is a point of "diminishing returns" at which increases in 25(OH)D are associated with increasingly small changes in the other variables. Vitamin D3 supplement doses of 0 IU (placebo; n=64), 400 IU [set as the current American Academy of Pediatrics recommendation (n=64)], 1,000 IU (n=64), 2,000 IU (n=64), and 4,000 IU (n=64) will be used in this 12-week (wintertime), double blind, randomized, placebo-controlled trial. To assess if racial differences exist in the biochemical responses to vitamin D supplementation, the groups will be stratified by race (white and black). Subjective measures of sun exposure will also be obtained to estimate the cutaneous synthesis of vitamin D. It is hypothesized that following 12 weeks of vitamin D supplementation, a dose-response relationship will be observed between vitamin D supplementation and equilibrium mean values of the following response variables: serum 25(OH}D, PTH and 1 ,25(OHhD, fractional calcium absorption, and biochemical markers of bone turnover. Our second hypothesis is that race will modify the responses of these intermediate endpoints of vitamin D and bone metabolism to increasing doses of oral vitamin D. This proposed dual-site and multidisciplinary project will address key research priorities identified in the 2006 DRI Research Synthesis Workshop and the 2007 Agency for Healthcare Research and Quality Evidence Report and will advance our understanding of the vitamin D needs of growing children based on serum 25(OH)D and intermediate endpoints of skeietai heaith. The findings from this study have important pubiic health implications with respect to vitamin D intake recommendations aimed at improving the health of US children.