Effects of Adrenal and Gonadal HR in Young Women with AN

描述(由申请人提供)：严重的骨量减少是神经性厌食症(AN)的一种常见且通常不可逆转的并发症。患有骨质疏松症的青少年通常峰值骨量减少，早期骨质疏松和骨折的风险增加。这些年轻女性的性腺类固醇和肾上腺雄激素脱氢表雄酮(DHEA)水平低于正常水平，这可能与她们的骨密度(BMD)低有关。低DHEA水平伴随着胰岛素样生长因子I(IGF-I)、雌激素和睾酮水平的下降。我们小组以前的数据表明，口服脱氢表雄酮治疗患有AN的年轻女性：增加了瘦体重、血清骨形成标记物和IGF-I的水平，并减少了骨吸收的尿标记物。我们还发现，标准激素替代疗法(HRT)显著降低了骨吸收标记物。关于这些疗法对骨骼强度和最终骨折风险的影响的信息缺乏。在这个项目中，我们将验证脱氢表雄酮和雌激素/孕激素联合治疗将通过合成代谢和抗骨溶解机制提高AN患者骨量的假设。我们将验证这样的假设，即18个月的DHEA+HRT将增加这些患者的骨密度和骨形成标记物，同时降低骨吸收标记物。这项拟议的研究将检验在这些年轻女性体内恢复正常的脱氢表雄酮和雌激素水平是否会在骨生长的关键时期增加骨量。这项研究还将研究DHEA对骨骼的合成代谢作用是否通过骨骼IGF-I调节系统来调节。使用双能X射线吸收测量仪(DXA)数据的横断面分析，我们还将测量骨骼结构几何指标，以确定这些年轻女性的机械强度是否受损，以及综合合成代谢/抗吸收治疗后强度是否恢复。为了获得关于年轻女性AN骨丢失和骨折风险机制的新信息，我们的研究目标是：具体目标1：通过随机对照试验，与安慰剂相比，测量18个月的DHEA+HRT疗程对骨量、骨转换标志物和血清IGF-I水平的影响。具体目标2：通过对DXA数据的横截面几何分析，确定与安慰剂相比，肾上腺和性腺类固醇替代联合治疗是否改变骨结构以增加强度。

DESCRIPTION (provided by applicant): Profound osteopenia is a frequent and often irreversible complication of anorexia nervosa (AN). Adolescents with AN often have a reduced peak bone mass and are at increased risk for early osteoporosis and fractures. These young women have subnormal serum levels of gonadal steroids and the adrenal androgen dehydroepiandrosterone (DHEA) that may be associated with their low bone mineral density (BMD). Low DHEA levels are accompanied by decreased levels of insulin-like growth factor I (IGF-I), estrogen, and testosterone. Previous data from our group indicate that oral DHEA therapy in young women with AN: increases lean body mass, serum levels of bone formation markers and IGF-I, and decreases urinary markers of bone resorption. We also found that standard hormonal replacement therapy (HRT) significantly decreased bone resorption markers. Information on the effects of these therapies on bone strength and ultimate fracture risk is lacking. In this project, we will test the hypothesis that combined therapy with DHEA and estrogen/progestin will enhance bone mass in patients with AN through anabolic and antiosteolytic mechanisms. We will test the hypothesis that 18 months of DHEA + HRT will increase BMD and markers of bone formation, while decreasing bone resorption markers in these patients. The proposed study will examine whether restoring normal levels of DHEA and estrogen in these young women will increase bone mass during a critical period for bone accretion. The study will also examine whether DHEA's anabolic effects on bone are mediated through the skeletal IGF-I regulatory system. Using cross-sectional analyses of dual energy x-ray absorptiometry (DXA) data, we will also measure indices of bone structural geometry to determine if mechanical strength is compromised in these young women, and if strength is restored in response to combined anabolic/antiresorptive therapy. To gain new information on the mechanisms underlying bone loss and fracture risk in young women with AN, our research goals are: Specific Aim 1: Through a randomized controlled trial, to measure the effects of an 18-month course of DHEA + HRT on bone mass, markers of bone turnover, and serum levels of IGF-I compared to placebo. Specific Aim 2: To determine whether combined therapy with adrenal and gonadal steroid replacement changes bone structure to increase strength compared to placebo, as assessed through cross-sectional geometric analysis of DXA data.