Renal Osteodystrophy: A Fresh Approach

肾性骨营养不良：一种新方法

• 批准号: 8235920
• 负责人: Hartmut H Malluche
• 金额: $ 29.29万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8235920
• 关键词: Address; Adult; Affect; Alkaline Phosphatase; Aluminum; Award; Awareness; Biochemical; Biochemical Markers; Biopsy; Blood; Blood Tests; Blood specimen; Bone Diseases; Bone Resorption; Cardiovascular system; Caring; Chronic Kidney Failure; Clinical Research; Clinical Sciences; Cost of Illness; DEXA; Detection; Development; Diagnosis; Dialysis procedure; Dual-Energy X-Ray Absorptiometry; Early identification; Foundations; Funding; Goals; Gold; Health; Health Care Costs; Histologic; Histology; International; Investigation; Kentucky; Kidney; Kidney Diseases; Laboratories; Letters; Link; Low Prevalence; Maintenance; Measurement; Measures; Medical; Minerals; Morbidity - disease rate; Osteogenesis; Osteoporosis; Outcome; Patients; Physiologic calcification; Prevalence; Prevention; Procedures; Procollagen; Protocols documentation; Quality of life; Renal Osteodystrophy; Resources; Serum Markers; Skeleton; TRANCE protein; Testing; Therapeutic; Time; Translational Research; Tumor necrosis factor receptor 11b; United States; United States National Institutes of Health; Universities; Vascular calcification; Vitamin D Analog; X-Ray Computed Tomography; base; bone; bone loss; bone mass; bone metabolism; bone turnover; burden of illness; calcification; cancer type; cerebrovascular; cohort; diagnosis standard; experience; follow-up; imaging modality; improved; inorganic phosphate; mineralization; mortality; novel; patient population; prevent; quality assurance; skeletal abnormality; tartrate-resistant acid phosphatase

DESCRIPTION (provided by applicant): Patients with chronic kidney disease (CKD) present with abnormalities in mineral and bone metabolism, which are associated with high morbidity and mortality. The most relevant bone abnormalities encompass suppressed or extremely elevated bone turnover and bone loss. Both turnover abnormalities and bone loss are associated with progressive calcifications, explaining the high morbidity and mortality. Bone biopsies are the gold standard for the diagnosis of bone abnormalities but are rarely performed. Noninvasive means to diagnose renal bone disease are urgently needed for implementation of targeted therapy to reduce morbidity and mortality. The long-term goal of the proposed study is to improve survival and quality of life in CKD patients by noninvasive detection of abnormalities in bone turnover and prevention of bone loss. This will allow administration of specific therapies and should contribute to reduction of disease burden and cost of a pervasive health problem affecting over 20 million patients in the United States. The central hypothesis is that renal osteodystrophy (ROD) can be defined noninvasively. Specifically, we will test the following hypotheses: 1. a) Bone volume component of ROD (bone loss) can be assessed by dual energy X-ray absorptiometry (DXA) and by quantitative computed tomography (QCT); however, QCT is more sensitive in recognizing bone loss; and, b) Bone loss occurs in patients with high and low turnover. Among patients with bone loss, there are at least 20% with low bone turnover. 2. The turnover component of ROD can be assessed noninvasively by PTH combined with established and/or novel biochemical markers of bone resorption and formation. The following specific aims will be pursued: 1. Comparison of DEXA and QCT for diagnosis of bone loss in CKD-5 patients and determination of the prevalence of low bone turnover in CKD-5 patients with bone loss. 2. Identification of the optimal combination of noninvasive tests for definition of the turnover component of ROD: For this purpose, 230 patients will be followed prospectively over 2 years, bone mass will be determined by QCT and DXA annually to establish the most sensitive means of identifying bone loss. Patients with osteoporosis at baseline and patients who develop bone loss at 1 or 2 years will be offered to undergo bone biopsy and blood drawing to measure serum markers of bone turnover, formation, and resorption. The best marker or combination of markers for definition of the turnover component ROD will be identified. Attainment of these goals will allow implementation of specific therapies without the use of invasive work-up and will assist in reducing morbidity, increasing survival, and improving quality of life in this unfortunate patient population. PUBLIC HEALTH RELEVANCE: Cardiovascular and cerebrovascular calcifications are linked to abnormalities in bone turnover and bone loss resulting in high morbidity and mortality. Bone turnover abnormalities and bone loss occur in chronic kidney disease patients and bone biopsy (an invasive test) is considered essential for diagnosis of these bone abnormalities. The proposed studies will establish noninvasive means (a panel of blood tests and imaging methods) for recognition and characterization of these bone abnormalities which has significant implications, regarding diagnosis, prevention, treatment and a better understanding of the pathogenic mechanisms.

描述(申请人提供)：慢性肾脏疾病(CKD)患者存在矿物质和骨代谢异常，这与高发病率和死亡率有关。最相关的骨异常包括抑制或极高的骨转换和骨丢失。周转异常和骨丢失都与进行性钙化有关，这解释了高发病率和死亡率。骨活检是诊断骨异常的金标准，但很少进行。为了实施靶向治疗以减少发病率和死亡率，迫切需要非侵入性手段来诊断肾性骨病。这项拟议研究的长期目标是通过非侵入性检测骨转换异常和预防骨丢失来改善CKD患者的生存和生活质量。这将允许管理特定的治疗方法，并应有助于减少疾病负担和影响美国2000多万患者的普遍健康问题的成本。中心假设是肾性骨营养不良(Rod)可以无创定义。具体地说，我们将检验以下假设：1.双能X射线吸收法(DXA)和定量计算机断层扫描(QCT)可以评估Rod的骨体积成分(骨丢失)；然而，QCT在识别骨丢失方面更敏感；以及，b)骨丢失发生在高转换和低转换的患者中。在骨丢失的患者中，至少有20%的人骨转换低。2.甲状旁腺激素结合已有的和/或新的骨吸收和形成生化标志物可以无创性地评价Rod的转换成分。研究的具体目的如下：1.比较DEXA和QCT对CKD-5患者骨丢失的诊断价值，并确定CKD-5患者中低骨转换的发生率。2.确定最佳无创性测试组合以确定Rod的转换成分：为此，将对230例患者进行2年以上的前瞻性随访，每年通过QCT和DXA测定骨量，以建立最敏感的骨丢失识别手段。基线水平的骨质疏松症患者和1-2年出现骨丢失的患者将接受骨活检和抽血，以测量骨转换、形成和吸收的血清标志物。将确定用于定义周转组件棒的最佳标记或标记组合。实现这些目标将允许在不使用侵入性检查的情况下实施特定的治疗方法，并将有助于降低发病率、提高存活率和改善这一不幸患者群体的生活质量。公共卫生相关性：心血管和脑血管钙化与骨转换异常和骨丢失有关，导致高发病率和死亡率。慢性肾脏病患者会出现骨转换异常和骨丢失，骨活检(一种侵入性检查)被认为是诊断这些骨异常的关键。拟议的研究将建立非侵入性手段(一组血液测试和成像方法)来识别和表征这些骨异常，这对于诊断、预防、治疗和更好地了解发病机制具有重要意义。