Nutritional and Hormonal Determinants of Peak Bone Mass

峰值骨量的营养和激素决定因素

• 批准号: 6709620
• 负责人: Madhusmita Misra
• 金额: $ 13.05万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6709620
• 关键词: adolescence (12-20); anorexia nervosa; body composition; bone density; bone metabolism; calcium metabolism; clinical research; dietary calcium; dietary supplements; estradiol; female; hormone sensitivity /resistance; human subject; insulinlike growth factor; lipid metabolism; nutrition related tag; osteoporosis; pathologic bone resorption; patient oriented research; protein biosynthesis; somatotropin; transdermal drug delivery; vitamin D; women' s health

DESCRIPTION (provided by applicant): Bone mineral accrual is maximum in adolescence and 90% of peak bone mass is achieved by 18 y of age. Insults suffered in adolescence can thus result in permanent deficits with increasd fracture risk in later life. Anorexia nervosa (AN) is associated with decreased bone formation and signifiant osteopenia and osteoporosis. Osteopenia is also more severe when AN begins in adolescence than in adult life. The pathogenesis of bone loss, however, is not well understood and no treatment has so far proven effective in treating low bone density (BMD) in adolescents with AN. Some improvement in BMD occurs with weight recovery, but a third of AN subjects remain osteoporotic. Calcium and vitamin D supplementation does not improve BMD in AN. Adults with AN have have high growth hormone (GH) and low IGF-I levels, suggestive of a nutritionally acquired 'GH resistance'. GH, both directly and through IGF-I, plays an important role in osteoblast differentiation. However, the presence of GH resistance in adolescents with AN in different pubertal stages, and the contribution of this 'resistance' to low BMD has not been examined. AN is associated with very low estrogen levels, but despite the known inhibitory effect of estrogen on bone resorption, oral estrogen was not effective in improving bone density in adults with AN. Oral estrogen suppresses IGF-I, and this may prevent the improvement in bone mass expected from anti-resorptioe effects of estrogen. Conversely, transdermal estrogen does not lower IGF-I, and the effects of transdermally administered estrogen on bone turnover in AN have not been examined. One aim of the proposal is to determine whether adolescents with AN are GH resistant, and whether this 'resistance' contributes to decreased bone formation and low bone density in AN. To investigate this hypothesis, we will examine GH secretory patterns in AN and matched controls, and determine if alterations in GH secretion predict changes in whole body metabolism, body composition, bone formation markers and BMD. We also hypothesize that administration of transdermal estrogen to mature adolescent girls with AN will result in decreased bone loss and increased bone formation (by increasing IGF-I levels). To investigate this hypothesis, we will examine bone metabolism in adolescent girls with AN before and six months after administration of transdermal estrogen. The effects of estrogen in weight recovered vs. non-weight recovered AN will also be studied.

描述（由申请人提供）： 骨矿物质的增加在青春期达到最大值，18岁时达到峰值骨量的90%。 因此，在青春期遭受的侮辱可能导致永久性的缺陷，并在以后的生活中增加骨折风险。 神经性厌食症（AN）与骨形成减少和显著的骨质减少和骨质疏松症有关。 当AN在青春期开始时，骨质减少也比成年时更严重。然而，骨丢失的发病机制还不清楚，迄今为止还没有治疗方法被证明对治疗AN青少年的低骨密度（BMD）有效。 随着体重的恢复，BMD也有一定的改善，但三分之一的AN受试者仍有骨质疏松。 补充钙和维生素D并不能改善AN的BMD。 成人AN具有高生长激素（GH）和低IGF-I水平，提示营养获得性“GH抵抗”。 GH直接或通过IGF-I在成骨细胞分化中起重要作用。 然而，生长激素抵抗在青少年AN在不同的青春期阶段的存在，这种“阻力”的低BMD的贡献还没有被检查。 AN与非常低的雌激素水平相关，但是尽管已知雌激素对骨吸收具有抑制作用，但口服雌激素对AN成人的骨密度改善无效。 口服雌激素抑制IGF-I，这可能会阻止预期的雌激素抗再吸收作用对骨量的改善。 相反，经皮雌激素不会降低IGF-I，经皮给药雌激素对AN患者骨转换的影响尚未研究。 该提案的一个目的是确定AN青少年是否具有GH抗性，以及这种“抗性”是否有助于AN中骨形成减少和骨密度降低。 为了研究这一假设，我们将检查生长激素分泌模式在AN和匹配的控制，并确定是否在生长激素分泌的变化预测全身代谢，身体成分，骨形成标志物和BMD的变化。 我们还假设，经皮给药雌激素与AN的成熟青春期女孩将导致减少骨丢失和增加骨形成（通过增加IGF-I水平）。 为了研究这一假设，我们将检查患有AN的青春期女孩在给予透皮雌激素之前和六个月后的骨代谢。 还将研究雌激素在体重恢复与体重未恢复的AN中的作用。