Chronic Kidney Disease and PTH: Effects on the Postmenopausal Skeleton

慢性肾脏病和 PTH：对绝经后骨骼的影响

• 批准号: 8311824
• 负责人: Emily Margaret Stein
• 金额: $ 14.98万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-10 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8311824
• 关键词: Affect; Awareness; Biochemical; Biochemical Markers; Biomechanics; Bone Density; Bone remodeling; Calcitriol; Characteristics; Chronic Kidney Failure; Competence; Data Set; Development Plans; Diagnostic; Dual-Energy X-Ray Absorptiometry; End stage renal failure; Finite Element Analysis; Fracture; General Population; Goals; Hip Fractures; Hormones; Hyperparathyroidism; Image; Individual; Instruction; Measurement; Measures; Mechanics; Medical center; Mentorship; Metabolic Bone Diseases; Modeling; Osteoporosis; Parathyroid gland; Patients; Peripheral; Phenotype; Physiology; Population; Postmenopausal Osteoporosis; Postmenopause; Principal Investigator; Recording of previous events; Renal function; Reporting; Research Personnel; Research Proposals; Research Training; Resolution; Risk; Scanning; Secondary Hyperparathyroidism; Serum; Site; Skeleton; Staging; Structure; Techniques; Training; United States; Universities; Woman; X-Ray Computed Tomography; base; bone; bone mass; bone quality; bone strength; career development; experience; instrument; interdisciplinary approach; meetings; new technology; older women; osteoporosis with pathological fracture; programs; skeletal; tomography; tool; treatment strategy

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.

影响美国数百万妇女的骨质疏松性骨折的风险可能会增加 慢性肾脏疾病（CKD）的共存。该跨学科的建议将阐明 绝经后骨骼的骨骼质量，微体系结构和强度上的中等CKD。我们将使用 骨矿物质密度（BMD），微体系结构，钙化激素的横截面深度分析 女性重塑的生化标志物，有和没有阶段3 CKD（60> GFR> 30 mL/min）和 有和没有脆弱性骨折的史。最先进的非侵入技术，高分辨率 外围计算机断层扫描（HRPQCT）和有限元分析（FEA）将使我们能够区分 小梁和皮质隔室，辨别小梁微结构细节和模型骨强度。 我们将比较患有CKD的妇女与原发性甲状腺运动（PHPT）的女性，以进一步探索 PTH对绝经后骨骼的影响。我们假设骨微体系结构和力量 基于CKD和断裂史将有所不同； CKD女性的生化变化将是 与微体系结构异常和强度降低相关； PTH对皮质的分解代谢作用 CKD和PHPT的女性将看到骨头。具体目的是：1）比较面积和体积 HRPQCT在骨折史和CKD中对妇女中骨骼质量和微体系结构的测量； 2） 通过骨折史和CKD比较女性中FEA的骨骼机械能力（强度）； 3）到 评估微体系结构与强度与PTH，其他钙称激素激素和强度之间的关系 重塑标记； 4）评估骨骼质量，微体系结构，强度和生化 pHPT的绝经后妇女的特征。该建议包括5年的职业发展 涉及跨学科指导和结构，生物力学和生化的培训的计划 骨质质量的评估，得到正式课程的支持。其中描述的研究和培训 建议将回答骨骼生理学的重要问题，同时推进我成为一个的目标 代谢骨疾病领域的独立研究者。 相关性（请参阅说明）： 该项目将产生有关轻度下降肾功能对骨骼的影响的信息 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 术后骨质疏松和CKD的绝经后妇女人口迅速增加的力量。 他们可能会强调将CKD和次级甲状旁腺功能亢进症纳入 绝经后骨质疏松症的诊断和治疗策略。