Bone Quality in Premenopausal Women with Idiopathic Fragility Fractures

描述（由申请人提供）：由于骨质疏松症在绝经后妇女中最常见，大多数明确的研究都检查了这一老年人群的流行病学、发病机制、诊断和治疗。骨质疏松症在绝经前妇女中诊断的频率要低得多。在相当比例的绝经前骨质疏松症妇女中，可发现继发原因，如糖皮质激素过量、乳糜泻或神经性厌食症。对病因的识别有助于指导临床管理。然而，一些年轻女性骨质疏松症没有明确的原因，并被称为特发性骨质疏松症（IOP）。在这些年轻女性中，目前关于病因或治疗的信息很少。本研究计划的目的是在健康的绝经前妇女中描述骨质疏松性骨障碍，这些妇女表现为低创伤性骨折，并且没有已知的潜在原因。在横断面病例对照研究中，将受影响妇女与正常妇女进行比较。临床、生化、激素、密度、放射学和组织形态学分析将被用来确定病例和对照组之间的差异。这一建议的核心是我们的假设，即绝经前妇女的IOP是一种骨质量紊乱。为了验证这一假设，我们将使用最先进的工具来测量骨质量的关键要素，包括骨周转率、几何形状、微结构和材料特性。无创技术，如中央定量计算机断层扫描和超高分辨率外围定量计算机断层扫描，一种非常新的方法，将用于确定骨几何形状，皮质和骨小梁的骨结构和连通性。经皮骨活检将通过定量静态和动态组织形态学进行分析。此外，新的活检分析技术将被用于确定骨的三维结构和强度以及骨矿物质和基质的材料特性。对年轻女性IOP障碍的描述是为受这种疾病影响的人制定有针对性的治疗策略的重要的第一步。此外，这个项目将允许我接受指导和培训，作为5年职业发展计划的一部分。因此，我将获得评估骨质量的技术和解释技能，这对我作为代谢性骨病领域的独立研究者的职业生涯是必要的。

DESCRIPTION (provided by applicant): Since osteoporosis is most common in postmenopausal women, most of the definitive studies have examined its epidemiology, pathogenesis, diagnosis, and treatment in this older population. Osteoporosis is diagnosed much less frequently in premenopausal women. In a substantial proportion of premenopausal women with osteoporosis, a secondary cause, such as glucocorticoid excess, celiac disease, or anorexia nervosa, is found. Identification of the contributing condition helps to guide clinical management. However, some young women with osteoporosis do not have a definable cause, and are said to have idiopathic osteoporosis (IOP). In these young women, there is very little information currently available on etiology or therapy. The goal of this research proposal is to characterize the osteoporotic bone disorder in otherwise healthy premenopausal women who present with low-trauma fractures, and who do not have a known underlying cause. Affected women will be compared to normal women in a cross-sectional, case-control study. Clinical, biochemical, hormonal, densitometric, radiographic, and histomorphometric analyses will be utilized to define differences between cases and control subjects. Central to this proposal is our hypothesis that IOP in premenopausal women is a disorder of bone quality. To test this hypothesis, we will use state-of-the-art tools to measure key elements of bone quality, including bone turnover, geometry, microarchitecture, and material properties. Noninvasive techniques such as central quantitative computed tomography and ultrahigh resolution peripheral quantitative computed tomography, a very new approach, will be used to determine bone geometry, cortical and trabecular bone structure and connectivity. A percutaneous bone biopsy will be obtained and analyzed by quantitative static and dynamic histomorphometry. In addition, newer biopsy analytic techniques will be utilized to determine the 3-dimensional structure and strength of bone and material properties of bone mineral and matrix. This characterization of the disorder of IOP in young women is an essential first step towards the development of targeted treatment strategies for those affected by this condition. In addition, this project will allow me to receive mentorship and training as part of a 5-year career development plan. I will thus acquire the technical and interpretive skills in the assessment of bone quality that will be necessary for my career as an independent investigator in the field of metabolic bone diseases.