RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF ORALCALCIUM SUPPLEMENTATION FOR OSTEO

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 骨量减少和骨折使患有Rett综合征(RTT)的女孩和妇女的临床过程复杂化。我们的研究表明，这些人中82%和57%的人全身骨矿含量(BMC)分别低于-1SD和-2SD(1)。本研究的目的是确定口服补钙治疗RTT女孩和妇女骨量减少的疗效。我们假设口服钙补充剂将通过减少骨矿物质吸收和增加骨矿物质沉积来逆转RTT女孩和妇女，特别是年龄较小的人的骨矿物质丢失的进程。为了验证这一假设，我们将使用双能X射线吸收法(DXA)测量54名RTT女孩和随机接受口服钙补充剂或安慰剂的妇女的BMC。测定尿钙排泄量和静脉血钙代谢标志物。骨折患病率将通过医学史进行记录，步行状态将通过临床检查进行评分。将进行体尺测量和人体测量，以表征生长和局部肌肉质量。将获得三天的食物记录和间隔药片计数，以监测遵守情况。我们预计口服补钙后BMC z评分将增加，尿钙排泄量将减少，从而逆转RTT女孩和妇女骨矿物质丢失的进程。由于RTT女孩和妇女的长寿，以及需要提供干预策略来预防与骨量减少相关的不良后果，这一信息对于确定这一点将是重要的。 本研究的目的是确定口服补钙治疗RTT女孩和妇女骨量减少的疗效和安全性。我们假设口服钙补充剂将通过减少RTT女孩和妇女的骨矿物质吸收和增加骨矿物质沉积来逆转骨矿物质丢失的进展，特别是在年轻人和老年人。 1.确定口服补钙是否导致RTT女孩和妇女的绝对BMC和BMC z-分数的DXA测量比安慰剂更大的增加 2.确定补钙是否导致青春期前RTT女孩的BMC和BMC z分数的绝对值比青春期后RTT女性的BMC和BMC z分数的增加更大 3.确定口服补钙是否比安慰剂更能减少RTT女孩和妇女的骨矿物质吸收，通过N-端肽和尿肌酸比率来衡量 4.确定口服钙补充剂是否导致RTT女孩和妇女的骨钙素和骨碱性磷酸酶测量的骨矿物质沉积比安慰剂增加。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Osteopenia and bone fractures complicate the clinical course of girls and women with Rett syndrome (RTT). Our studies show that total body bone mineral content (BMC) is below -1 SD and -2 SD in 82% and 57% of these individuals, respectively (1). The purpose of this study is to determine the efficacy of oral calcium (Ca) supplementation in the treatment of osteopenia in RTT girls and women. We hypothesize that oral Ca supplementation will reverse the progression of bone mineral loss in RTT girls and women, particularly in younger than older individuals, by reducing bone mineral resorption and increasing bone mineral deposition. To test this hypothesis, we will measure BMC using duel energy x-ray absorptiometry (DXA) in 54 RTT girls and women randomized to receive oral Ca supplements or placebo. Urinary Ca excretion and venous markers of Ca metabolism will be measured. Bone fracture prevalence will be documented by medcal history and ambulatory status will be scored by clinicalexamination. Stadiometric and anthropometric measurements will be performed to characterize growth and regional muscle mass. Three-day food records and interval pill count will be obtained to monitor compliance. We anticipate that BMC z-scores will increase and urinary Ca wasting will decrease with oral Ca supplementation thereby reversing the progression of bone mineral loss in RTT girls and women. This information will be important to ascertain because of the longevity of RTT girls and women and the need to provide interventional strategies that prevent the adverse consequences associated with osteopenia. The purpose of this study is to determine the therapeutic efficacy and safety of oral Ca supplementation in the treatment of osteopenia inRTT girls and women. We hypothesize that oral Ca supplementation will reverse the progression of bone mineral loss, particularly in younger than in older individuals, by decreasing bone mineral resorption and increasing bone mineral deposition in RTT girls and women. 1. To determine if oral Ca supplements result in a greater increase in absolute BMC and BMC z-scores, measured byDXA, than placebo inRTT girls and women 2. To determine if Ca supplements result in a greater increase in absolute BMC and BMC z-scores in pre-pubertal RTT girls than in post-pubertal RTT women 3. To determine if oral Ca supplements result in a greater reduction in bone mineral resorption, measured by N-telopeptides and urinary Cacreatinine ratios, than placebo in RTT girls and women 4. To determine if oral Ca supplements result in increased bone mineral deposition, measured by osteocalcin and bone alkaline phosphatase, than placebo in RTT girls and women.