Supplemental zinc and bone turnover in early pubertal females

描述（由申请人提供）：在我们对钙和维生素D与骨骼健康的理解方面已经取得了重大成就，然而，大量科学证据也已经确定了尚未充分研究的营养素，这些营养素具有减轻骨质疏松症负担的潜力。锌在骨代谢中起着重要作用，动物和人类研究表明，除了在缺锌条件下纠正骨骼和生长损伤外，补充锌可能具有促进骨骼健康的作用。锌对骨代谢的作用部分是由igf - 1介导的。在进行长期骨骼试验之前，建议进行短期锌补充试验，首先确定锌是否会改变健康的青春期早期女性（9-10.5岁）骨骼代谢的中间标志物。我们假设，与服用安慰剂的女性相比，在3周内每天服用24毫克锌的健康女性，其骨形成和血浆生长因子的血清标志物会升高。我们进一步假设锌组和安慰剂组之间的差异会因种族而异。为了验证这些假设，我们将筛选青春期早期的女性，以确保相似的成熟状态，并进行为期3周的随机、双盲、安慰剂对照试验，其中锌补充剂（硫酸锌；n=80）和安慰剂（n=80）组。这些小组将进一步按种族划分（非西班牙裔白人和非西班牙裔黑人；每组n=40）。具体目的是确定与接受安慰剂的女性相比，早期青春期女性补充锌是否会有：1)有利于骨形成的骨转换标志物增加更多；2)血浆IGF-1和IGFBP-3显著升高；3)不同种族的骨转换标志物IGF-1和IGFBP-3的变化。此外，人体测量、成熟度偏移、性成熟、红细胞超氧化物歧化酶活性、铜蓝蛋白、饮食摄入量和身体活动也将被确定。本研究结果将为补充锌是否是一种改善年轻女性骨转换生化指标和生长因子的可行营养策略提供初步证据。此外，研究结果将有助于确定长期临床骨试验是否有必要更明确地评估补充锌降低骨质疏松症风险的潜力。

DESCRIPTION (provided by applicant): Significant accomplishments have been achieved with respect to our understanding of calcium and vitamin D and skeletal health, yet a body of scientific evidence has also identified understudied nutrients that have potential for reducing the burden of osteoporosis. Zinc has important roles in bone metabolism and there are indications from animal and human studies that beyond correcting skeletal and growth impairments under deficiency conditions, supplementation with zinc may have a bone health-promoting role. It has been postulated that the action of zinc on bone metabolism is partially mediated by IGF-I. Prior to undertaking a long-term bone trial, a short-term zinc supplementation trial is proposed to first determine if zinc alters intermediate markers of bone metabolism in healthy, early pubertal females (9-10.5 years of age). We hypothesize that healthy females receiving 24 mg zinc /day over 3 weeks will have elevated serum markers of bone formation and plasma growth factors compared to those receiving placebo. We further hypothesize that the differences between the zinc and placebo groups will vary by race. To test these hypotheses, we will screen early pubertal females to assure similar maturational status and conduct a 3-week, randomized, double-blind, placebo-controlled trial with a zinc supplementation (zinc sulfate; n=80) and a placebo (n=80) arm. The groups will be further divided by race (non-Hispanic White and non-Hispanic Black; n=40 per group). The specific aims are to determine if early pubertal females supplemented with zinc compared to those receiving placebo will have: 1) greater increases in markers of bone turnover favoring bone formation; 2) greater increases in plasma IGF-1 and IGFBP-3; and 3) changes in bone turnover markers, IGF-1 and IGFBP-3 that differ by race. In addition, anthropometric measures, maturity offset, sexual maturation, erythrocyte superoxide dismutase activity, ceruloplasmin, dietary intakes and physical activity will be determined. Findings from this study will provide preliminary evidence of whether supplementation with zinc is a viable nutrition strategy to improve biochemical indices of bone turnover and growth factors in young females. Moreover, the results will help determine if a long-term clinical bone trial is warranted to more definitely assess the potential for supplemental zinc to reduce the risk for osteoporosis.