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被定义为骨质疏松症 这种情况发生在性腺功能完好、身体健康的年轻女性身上 没有继发性骨丢失原因。 绝经前妇女的眼压是一种罕见的疾病。估计的流行率 在美国，基于有记录的低创伤骨折或 低股骨颈骨密度(BMD)，大约为113,000。目前还没有FDA批准的治疗绝经前眼压的方法，她们中的许多人都有多处骨折或骨密度极低。 这项建议寻求进行二期临床试验，以调查其疗效和安全性 人重组甲状旁腺激素对绝经前妇女眼压的影响。 它是基于我们之前的工作，在我们的工作中，我们定义了这种疾病的微结构异常：皮质变薄，小梁丢失，小梁板减少， 更少和更长的小梁杆，杆和杆之间的连接性降低 板材，以及降低的硬度或强度。 我们将验证一个中心假设，即合成代谢疗法使用特瑞帕帝，一种药物 增加成骨细胞介导的骨形成，将安全地增加有IOP的绝经前妇女的真实和体积骨密度。我们还将检验这一假设 该药物可使异常微结构恢复至正常状态，并改善 绝经前眼压的骨质量的其他方面。 在这项随机和安慰剂对照的2期临床试验中，我们将 描述特瑞帕帝对面骨密度和体积骨密度、微结构 患有眼压的女性眼压的重塑、僵硬、矿化和胶原特性。 我们将使用最先进的和新的方法来进行骨骼宏观和微观成像，这些方法从未应用于眼压的治疗。这些新方法将为绝经前妇女急需的眼压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 为了解决眼压治疗和改善患有不明原因骨质疏松症的年轻女性的健康问题，这项建议解决了美国食品和药物管理局S孤儿产品开发门诊赠款计划的一个关键目标，即支持临床开发用于罕见疾病或目前尚不存在治疗方法的情况下的产品。

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.