Chronic Kidney Disease and PTH: Effects on the Postmenopausal Skeleton

描述（由申请人提供）： 在美国，影响数百万妇女的骨质疏松性骨折的风险可能会因慢性肾脏病（CKD）的共存而增加。这个跨学科的建议将阐明中度CKD对绝经后骨骼的骨量、微结构和强度的影响。我们将使用一个横断面，深入分析骨矿物质密度（BMD），微结构，促钙激素和生化标志物的重塑妇女，有和没有3期CKD（60>GFR>30 ml/min）和有和没有脆性骨折的历史。最先进的非侵入性技术，高分辨率外周计算机断层扫描（HRpQCT）和有限元分析（FEA），将使我们能够区分骨小梁和皮质间室，辨别骨小梁微观结构的细节和模型骨强度。我们将比较CKD妇女与原发性甲状旁腺功能亢进（PHPT）妇女，以进一步探讨PTH对绝经后骨骼的影响。我们假设，骨微结构和强度将根据CKD和骨折的历史而不同; CKD女性的生化变化将与异常的微结构和强度降低相关; PTH对皮质骨的分解代谢作用将在CKD和PHPT女性中观察到。具体目标是：1）通过HRpQCT比较骨折史和CKD女性的骨量和微结构的面积和体积测量值; 2）比较骨机械能力3）评估微结构和强度与PTH、其他促钙激素和重塑标志物之间的关系;评估绝经后PHPT妇女的骨量、骨微结构、骨强度和生化特征。该提案包括一个为期5年的职业发展计划，涉及骨质量的结构，生物力学和生物化学评估方面的跨学科指导和培训，并得到正式课程的支持。本提案中描述的研究和培训将回答骨骼生理学中的重要问题，同时推进我成为代谢性骨病领域独立研究者的目标。 公共卫生相关性：该项目将产生有关绝经后妇女肾功能轻度下降对骨骼影响的信息。我们的研究结果将提高人们对影响骨质疏松症和CKD绝经后妇女人群中骨骼结构和强度的独特因素的认识。他们可能强调将CKD和继发性甲状旁腺功能亢进纳入绝经后骨质疏松症的诊断和治疗策略的重要性。

DESCRIPTION (provided by applicant): The risk of osteoporotic fracture, which affects millions of women in the United States, may be increased by the coexistence of chronic kidney disease (CKD). This interdisciplinary proposal will elucidate the effects of moderate CKD on bone mass, microarchitecture, and strength in the postmenopausal skeleton. We will use a cross-sectional, in-depth analysis of bone mineral density (BMD), microarchitecture, calciotropic hormones and biochemical markers of remodeling in women, with and without stage 3 CKD (60>GFR>30 ml/min) and with and without a history of fragility fracture. State of the art non-invasive techniques, high-resolution peripheral computed tomography (HRpQCT) and finite element analysis (FEA), will allow us to distinguish trabecular and cortical compartments, discern trabecular microstructural details and model bone strength. We will compare women with CKD to women with primary hyperparathyroism (PHPT) to further explore the effects of PTH on the postmenopausal skeleton. We hypothesize that bone microarchitecture and strength will differ based upon history of CKD and fracture; biochemical changes in women with CKD will be associated with abnormal microarchitecture and decreased strength; catabolic effects of PTH on cortical bone will be seen in women with CKD and PHPT. The specific aims are: 1) to compare areal and volumetric measurements of bone mass and microarchitecture by HRpQCT in women by fracture history and CKD; 2) to compare bone mechanical competence (strength) by FEA in women by fracture history and CKD; 3) to assess relationships between microarchitecture and strength with PTH, other calciotropic hormones, and remodeling markers; and 4) to assess bone mass, microarchitecture, strength and biochemical characteristics in postmenopausal women with PHPT. This proposal includes a 5-year career development plan involving interdisciplinary mentorship and training in structural, biomechanical and biochemical assessment of bone quality, supported by formal coursework. The research and training described in this proposal will answer important questions in skeletal physiology while advancing my goal of becoming an independent investigator in the field of metabolic bone diseases. PUBLIC HEALTH RELEVANCE: This project will generate information about the impact of mild declines in kidney function on the skeleton in postmenopausal women. Our findings will increase awareness of unique factors that affect skeletal structure and strength in the rapidly increasing population of postmenopausal women with osteoporosis and CKD. They may emphasize the importance of incorporating CKD and secondary hyperparathyroidism into diagnostic and treatment strategies for postmenopausal osteoporosis.