Idiopathic Osteoporosis in Premenopausal Women

绝经前妇女的特发性骨质疏松症

• 批准号: 7988513
• 负责人: Elizabeth J Shane
• 金额: $ 19.05万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-05 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7988513
• 关键词: Accounting; Address; Adipocytes; Adverse effects; Anabolic Agents; Award; Biological databases; Biopsy; Bone Density; Bone remodeling; Cellular biology; Clinical Investigator; Data; Defect; Disease; Enrollment; Etiology; Faculty; Fatty acid glycerol esters; Fracture; Funding; Future; Goals; Grant; Health; Heterogeneity; Human; Image; K-Series Research Career Programs; Longevity; Marrow; Mentors; Minerals; Mission; Osteoblasts; Osteoclasts; Osteocytes; Osteogenesis; Osteoporosis; Parathyroid Hormones; Pathogenesis; Population; Postmenopausal Osteoporosis; Predictive Value; Premenopause; Property; Public Health; Recombinants; Research; Research Personnel; Research Proposals; Skeleton; Specimen; Structure; Testing; Time; Training; Trauma; Tweens; United States National Institutes of Health; Woman; base; bone; bone cell; bone loss; bone mass; bone quality; bone strength; bone turnover; clinical phenotype; density; human PTH protein; improved; indexing; insight; interest; mineralization; novel; novel strategies; parathyroid hormone (1-34); patient oriented research; programs; response; retinal rods; skeletal; skeletal disorder

DESCRIPTION (provided by applicant): The goal of this renewal application is to provide continued support for my mentoring program for junior faculty and fellows interested in patient- oriented research (POR). During my first K24, 2 junior faculty completed K awards, one received an R01 and 4 were awarded new K23s, a highly successful record. My future research goals are to conduct high quality POR elucidating cellular and structural mechanisms that underlie deficits in bone strength associated with postmenopausal osteoporosis, idiopathic osteoporosis (IOP) in premenopausal women, and other diseases associated with adverse effects on the skeleton. My mentoring goals are to use currently and newly funded projects to provide high quality mentoring and training for new clinical investigators in POR. During the grant, we defined consistent microarchitectural abnormalities of bone quality in women with IOP: thin cortices, trabecular loss, decreased connectivity, stiffness and mineralization. Despite some heterogeneity, the majority had low or normal remodeling. In the renewal, we will test the hypotheses that microarchitectural abnormalities in premenopausal women with IOP are related to abnormal formation, function or lifespan of bone cells, particularly osteoblasts and that PTH(1-34), a bone anabolic agent, can reverse the structural and dynamic abnormalities we have defined. We will use established and novel approaches to skeletal macro- and micro-imaging and cell biology that will provide novel insights into mechanisms of bone loss in IOP and a rational basis for its therapy. This proposal, as well as databases, biological specimens and imaging data from other currently and newly funded projects, will provide me with many opportunities to mentor junior investigators in POR and will also provide me with protected time to focus on training and mentoring. By investigating the causes and therapy of IOP, improving the health of young women with unexplained fractures, and permitting me to devote more time to POR and to training and mentoring junior faculty and fellows in POR, this proposal addresses several key missions of NIH.

描述（由申请人提供）：此更新申请的目的是为我的初级教师和对患者研究感兴趣的研究员（POR）提供我的指导计划的持续支持。在我的第一个K24中，有2个初级教师完成了K奖，其中一名获得了R01和4的奖项，获得了新的K23，这是一项非常成功的纪录。我未来的研究目标是阐明与绝经前妇女的绝经后骨质疏松症，特发性骨质疏松症（IOP）相关的骨骼强度缺陷的细胞和结构机制，这些骨骼强度和其他疾病以及其他与对骨架的不良影响相关的疾病。我的指导目标是使用当前和新资助的项目为POR的新临床研究人员提供高质量的指导和培训。在赠款期间，我们定义了IOP女性骨质质量的一致的微体系式异常：薄皮层，小梁损失，连通性降低，僵硬和矿化。尽管有一些异质性，但大多数的重塑较低或正常。在续签中，我们将测试假设IOP的绝经前妇女的微构造异常与骨细胞的异常形成，功能或寿命有关，尤其是成骨细胞（尤其是骨细胞）和PTH（1-34）（1-34）（1-34）（1-34），骨骼验应剂，一种骨骼验应剂，可以反转结构性和动态性，我们的结构和动态性均定为定义。我们将使用已建立的新方法来进行骨骼宏观和微观图像和细胞生物学，这些方法将提供有关IOP中骨质流失机制的新颖见解，以及其治疗的合理基础。该提案以及数据库，来自其他当前和新资助的项目的生物标本和成像数据，将为我提供很多机会来指导POR的初级调查人员，还将为我提供受保护的时间，以专注于培训和指导。通过调查IOP的原因和治疗，改善了无法解释的骨折的年轻妇女的健康，并允许我花更多的时间去POR，培训和指导POR中的初级教师和研究员，该提议介绍了NIH的几项关键任务。