TERIPARATIDE (FORTEO) FOR INCREASING BONE MASS

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。子项目及 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。 成骨不全是一种遗传性I型胶原显性遗传病，以多发性骨折和骨脆性骨折为特征。 OI影响所有种族和族裔的每10，000人中约1至2人。 有没有治愈成骨不稳，这是没有建立的医疗治疗成人与障碍。 本研究的目的是确定特立哌齐（FORTEO）在成人成骨不全（OI）患者中增加骨量和改善骨结构的有效性。 没有关于甲状旁腺激素（PTH）治疗OI的有用性的数据。 一种有效的合成代谢疗法可用于治疗成人患者的OI将是一个非常有吸引力的和宝贵的资产，不仅对受影响的患者，而且对整个医学界。 工作假设是，患有OI的个体接受teriparbital治疗后，脊柱和髋骨矿物质密度增加，骨几何结构改善（骨宽度和皮质厚度增加）。 OI的潜在病理生理学是I型胶原（骨中最丰富的蛋白质）合成的定量或定性异常。 尽管预期特立帕替尼不会改变所产生的胶原蛋白中的缺陷，但预期其会增加所形成的骨的量。 因此，我们假设通过增加骨密度，OI患者的整体骨强度将增强，骨折发生率将降低。 这是一项多中心临床疗效和安全性研究，将采用随机化、安慰剂对照和双盲研究。 将参与的三个临床研究中心是俄勒冈州健康科学大学（里德/奥沃尔/施泰纳）、约翰霍普金斯大学（夏皮罗）和凯斯西大学（沃曼）。 将通过Osteoporosis Imperfecta Foundation从诊所名册和公告中招募90名患有OI的成年人（任何类型-每个研究中心35名），进行为期18个月的PTH（20 mcg/天）安慰剂对照双盲试验。 仅近期无抗骨吸收药物治疗史的受试者（初治）将被纳入本研究。 主要结局变量为BMD，但也将评估各种其他变量，包括骨重建的血清和尿液标志物、骨结构的定量计算机断层扫描（QCT）测量和安全性参数。 将收集DNA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.