TERIPARATIDE (FORTEO) FOR INCREASING BONE MASS

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。 成骨不全是一种遗传性常染色体显性遗传性I型胶原疾病，以多发性骨折和骨脆性骨折为特征。在所有种族和民族血统的每10,000人中，约有1至2人感染OI。对于成骨不完全症没有治愈方法，这也不是对患有这种疾病的成年人的既定药物治疗。 本研究的目的是确定特立帕替特(FORTEO)对成骨不全(OI)患者增加骨量和改善骨结构的效果。没有关于甲状旁腺激素(PTH)治疗OI的有效性的数据。可用于治疗成人OI患者的有效合成代谢疗法不仅对受影响的患者而且对整个医学界都是一项极具吸引力和宝贵的财富。 工作假设是，受OI影响的患者在接受Teriparatide治疗后，脊柱和髋骨的矿物质密度将会增加，骨几何结构也会得到改善(骨宽度和皮质厚度增加)。OI的潜在病理生理学基础是I型胶原合成的数量或质量的异常，I型胶原是骨骼中含量最丰富的蛋白质。尽管Teriparatide预计不会改变所产生的胶原蛋白的缺陷，但它有望增加骨形成的数量。因此，我们假设，通过增加骨密度，OI的整体骨强度将得到增强，骨折发生率将会降低。 这是一项多点临床疗效和安全性研究，将随机、安慰剂对照和双盲进行。将参加的三个临床站点是俄勒冈健康科学大学(Reeder/Orwoll/Steiner)、约翰霍普金斯大学(Shapiro)和凯斯西大学(Warman)。90名成人OI(每个站点35种类型)将通过骨质疏松症基金会从临床登记和公告中招募，进行为期18个月的安慰剂对照双盲甲状旁腺素试验(每天20mcg)。只有那些近期没有接受过抗吸收药物治疗的受试者才会被纳入这项研究。 主要的结果变量将是骨密度，但也将评估各种其他变量，包括血清和尿骨重塑标记物、骨结构的定量计算机断层扫描(QCT)测量和安全参数。DNA将被收集起来，用于未来可能的分析。

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. Osteogenesis imperfecta is an inherited autosomal dominant disorder of type I collagen characterized by multiple fractures and bone fragility fractures. OI affects approximately 1 to 2 out of every 10,000 individuals of all racial and ethnic origins. There is no cure for osteogenesis imperfecta and this is no established medical therapy for adults with the disorder. The purpose of this study is to determine the effectiveness of teriparatide (FORTEO) for increasing bone mass and improving bone structure in adults affected with Osteogenesis Imperfecta (OI). There are no data concerning the usefulness of parathyroid hormone (PTH) therapy in OI. An effective anabolic therapy available for the treatment of adult patients with OI would be an extremely attractive and valuable asset not only to the affected patients but also to the medical community at large. The working hypothesis is that individuals affected with OI who are treated with teriparatide will experience increased spine and hipbone mineral density and improvements in bone geometry (an increase in bone width and cortical thickness). The underlying pathophysiology of OI is a quantitative or qualitative abnormality in the synthesis of type I collagen, the most abundant protein in bone. Although teriparatide is not expected to change the defect in the collagen produced, it is expected to increase the quantite of bone formed. Therefore, we hypothesize that by increasing bone mineral density, overall bone strength will be enhanced in OI and fracture incidence will be reduced. The is a multi-site clinical efficacy and safety study that will be randomized, placebo-controlled and double-blinded. The three clinical sites that will participate are Oregon Health Sciences University (Reeder/Orwoll/Steiner), Johns Hopkins University (Shapiro), and Case Western University (Warman). Ninety adults with OI (of any type - 35 at each site) will be recruited from clinic rolls and announcements via the Osteoporosis Imperfecta Foundation for an 18-month placebo controlled, double-blinded trial of PTH (20mcg/day). Only those subjects who have no recent history of being treated with antiresorptive agents (treatment-naive) will be included in the study. The primary outcome variable will be BMD, but a variety of other variables will also be assessed including serum and urine markers of bone remodeling, quantitative computed tomography (QCT) measures of bone structure and safety parameters. DNA will be collected for possible future analyses.