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，基于血清甲状旁腺激素（PTH）浓度、钙吸收和骨折率，已建议将达到血清25（OH）D-50 nmol/L作为充足的目标。在年轻人群中，循环25（OH）D的最佳水平尚未明确定义，也不知道什么功能结局指标是定义该水平的理想指标。此外，不知道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方和南方地区的青春期早期男性（10至13岁; n=160）和女性（9至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了维生素D和骨代谢的中间终点[即，血清25（OH）D、PTH和1，25（OHhD、钙吸收分数和骨转换的生化标志物）; 2）种族是否改变维生素D和骨代谢的这些中间终点对维生素D补充剂的反应;（3）阐明25个基因之间的关系（OH）D浓度和血清PTH、1，25（OH）2D和钙吸收分数中的每一个变量，特别感兴趣的是确定是否存在一个“收益递减”点，在该点上，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）、双盲、随机、安慰剂对照试验中，将使用0 IU（安慰剂; n = 64）、400 IU [设定为当前美国儿科学会推荐（n = 64）]、1，000 IU（n = 64）、2，000 IU（n=64）和4，000 IU（n=64）的维生素D3补充剂剂量。为了评估对维生素D补充的生化反应是否存在种族差异，将按种族（白色和黑人）对各组进行分层。还将获得阳光照射的主观测量值，以估计维生素D的皮肤合成。假设在维生素D补充12周后，将在维生素D补充和以下响应变量的平衡平均值之间观察到剂量-响应关系：血清25（OH）D、PTH和1，25（OH）hD、钙吸收分数和骨转换的生化标志物。我们的第二个假设是，种族将改变维生素D和骨代谢的这些中间终点对口服维生素D剂量增加的反应。这个拟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年医疗保健研究和质量证据报告机构中确定的关键研究优先事项，并将促进我们对基于血清25（OH）D和骨骼健康中间终点的生长儿童维生素D需求的理解。这项研究的结果对于旨在改善美国儿童健康的维生素D摄入建议具有重要的公共健康意义。

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.