Phase 2 Teriparatide for Tx of Idiopathic Osteoporosis in Premenopausal Women

绝经前妇女的特发性骨质疏松症（IOP）被定义为骨质疏松症 这种情况发生在年轻的、其他方面健康的、性腺功能完整的女性身上， 无继发性骨质流失。 绝经前妇女的IOP是一种罕见的疾病。估计患病率 在美国，基于有记录的低创伤骨折或 低股骨颈骨矿物质密度（BMD）约为113，000。对于患有IOP的绝经前妇女，没有FDA批准的治疗方法，其中许多人患有持续的多处骨折或具有极低的BMD。 该提案寻求进行2期临床试验，以研究其疗效和安全性 的替立哌酮，人重组PTH，用于绝经前妇女的IOP。 这是基于我们以前的工作，我们已经定义了这种疾病的微结构异常：薄皮质，小梁损失，小梁板减少， 小梁杆更少更长，杆之间的连接性降低， 板，并降低刚度或强度。 我们将测试中心的假设，合成代谢治疗与teriparlitazone，一种药物， 增加成骨细胞介导的骨形成，将安全地增加绝经前IOP女性的真实的和体积BMD。我们还将检验假设 该teriparterium将恢复异常的微观结构向正常，并改善 绝经前IOP中骨质量的其他方面。 在这项随机和安慰剂对照的2期临床试验中，我们将 表征teriparbine对面积和体积BMD，微结构， 重塑、硬度、矿化和胶原蛋白特性。 我们将使用最先进的和新颖的方法来进行骨骼宏观和微观成像，这些方法从未应用于IOP的治疗。这些新方法将为绝经前妇女急需的IOP治疗方法提供合理的基础，并将对临床实践产生重大影响。通过调查 为了治疗IOP和改善患有不明原因骨质疏松症的年轻女性的健康，该提案解决了FDA孤儿产品开发办公室OPD资助计划的关键目标，即支持用于罕见疾病或目前没有治疗方法的疾病的产品的临床开发。

Idiopathic osteoporosis(IOP)in premenopausal women is defined as osteoporosis that occurs in young, otherwise healthy women with intact gonadal function and no secondary cause of bone loss. IOP in premenopausal women is an uncommon disorder. The estimated prevalence in the United States, based on women with documented low trauma fractures or low femoral neck bone mineral density (BMD), is approximately 113,000.There is no FDA-approved therapy for premenopausal women with IOP, many of whom have sustained multiple fractures or have extremely low BMD. This proposal seeks for a Phase 2 clinical trial to investigate the efficacy and safety of teriparatide, human recombinant PTH, for IOP in premenopausal women. It is based upon our previous work in which we have defined microarchitectural abnormalities in this disorder: thin cortices, trabecular loss, fewer trabecular plates, fewer and longer trabecular rods, decreased connectivity between rods and plates, and reduced stiffness or strength. We will test the central hypothesis that anabolic therapy with teriparatide, a drug that increases osteoblast-¿mediated bone formation, will safely increase a real and volumetric BMD in premenopausal women with IOP. We will also test the hypothesis that teriparatide will restore abnormal microstructure towards normal, and improve other aspects of bone quality in premenopausal IOP. In this phase 2 clinical trial, which is randomized and placebo-¿controlled, we will characterize effects of teriparatide on areal and volumetric BMD, microarchitecture, remodeling, stiffness, mineralization and collagen properties in women with IOP. We will use both state-¿of-¿the-¿art and novel approaches to skeletal macro-¿and micro-imaging that have never been applied to the therapy of IOP. These new approaches will provide a rational basis for a much-needed therapeutic approach to IOP in premenopausal women and will have high impact upon clinical practice. By investigating the therapy of IOP and improving the health of young women with unexplained osteoporosis, this proposal addresses a key goal of the FDA¿s Office of Orphan Product Development OPD grant program,namely to support the clinical development of products for use in rare diseases or conditions where no current therapy exists.