RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF ORALCALCIUM SUPPLEMENTATION FOR OSTEO

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 骨量减少和骨折使Rett综合征（RTT）女孩和妇女的临床病程复杂化。 我们的研究表明，82%和57%的个体的全身骨矿物质含量（BMC）分别低于-1 SD和-2 SD（1）。 本研究的目的是确定口服钙（Ca）补充剂治疗RTT女孩和妇女骨质减少的疗效。 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女孩和妇女的骨矿物质丢失的进展，特别是在比老年人年轻的个体中。 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。 将测量尿钙排泄和钙代谢的静脉标志物。 骨折患病率将通过病史记录，门诊状态将通过临床检查评分。 将进行测距和人体测量，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丸计数，以监测依从性。 我们预计，口服钙补充剂将增加BMC z评分，减少尿钙浪费，从而逆转RTT女孩和妇女骨矿物质丢失的进展。 由于RTT女孩和妇女的寿命较长，并且需要提供预防骨质减少相关不良后果的干预策略，因此确定这些信息非常重要。 本研究的目的是确定口服钙补充剂治疗RTT女孩和妇女骨质疏松症的疗效和安全性。 我们假设口服钙补充剂将逆转骨矿物质丢失的进展，特别是在年轻人比老年人，通过减少骨矿物质吸收和增加骨矿物质沉积在RTT女孩和妇女。 1. 为了确定口服钙补充剂是否会导致RTT女孩和妇女的绝对BMC和BMC z分数（通过DXA测量）比安慰剂更大的增加， 2. 确定钙补充剂是否导致青春期前RTT女孩的绝对BMC和BMC z评分比青春期后RTT女性更大的增加 3. 确定口服钙补充剂是否导致RTT女孩和妇女的骨矿物质吸收（通过N-端肽和尿钙蛋白比值测量）比安慰剂更大的降低 4. 确定口服钙补充剂是否会导致RTT女孩和女性的骨矿物质沉积增加（通过骨钙素和骨碱性磷酸酶测定），而不是安慰剂。

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.