Chronic Kidney Disease and PTH: Effects on the Postmenopausal Skeleton

在美国，影响数百万妇女的骨质疏松性骨折的风险可能会增加， 慢性肾脏病（CKD）并存。这一跨学科的建议将阐明的影响， 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 对骨矿物质密度（BMD）、微结构、促钙激素进行横断面深入分析 和有和没有3期CKD（60>GFR>30 ml/min）的女性中重塑的生化标志物， 有无脆性骨折史。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 骨小梁和皮质隔室，辨别骨小梁微观结构细节和模型骨强度。 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。我们假设骨骼的微结构和强度 将根据CKD和骨折史而有所不同; CKD女性的生化变化将是 与异常微结构和强度降低相关; PTH对皮质骨的分解代谢作用 在患有CKD和PHPT的女性中将看到骨。具体目的是：1）比较面积和体积 根据骨折史和CKD，通过HRpQCT测量女性的骨量和微结构; 2） 通过FEA比较骨折史和CKD女性的骨机械能力（强度）; 3） 评估微结构和强度与PTH、其他促钙激素之间的关系， 重塑标志物;以及4）评估骨量、微结构、强度和生化指标， 绝经后PHPT妇女的特征。该计划包括5年的职业发展 涉及结构、生物力学和生物化学方面跨学科指导和培训的计划 骨质量的评估，由正式课程的支持。本文所述的研究和培训 这项提案将回答骨骼生理学中的重要问题，同时推进我成为一名 代谢性骨病领域的独立研究者。 相关性（参见说明）： 该项目将产生有关肾功能轻度下降对骨骼影响的信息， 绝经后妇女。我们的发现将提高人们对影响骨骼结构的独特因素的认识 和强度在绝经后妇女骨质疏松症和慢性肾脏病的人口迅速增加。 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。

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. RELEVANCE (See instructions): 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.