CHANGES IN SKELETAL MICROARCHITECTURE FOLLOWING RENAL TRANSPLANTATION

肾移植后骨骼微结构的变化

• 批准号: 8144171
• 负责人: Mary Beth Leonard
• 金额: $ 43.63万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8144171
• 关键词: Address; Adult; Age; Architecture; Area; Biological Markers; Biopsy; Bone Density; Characteristics; Child; Chronic Kidney Failure; Data; Deformity; Deterioration; Diagnostic tests; Dialysis patients; Dialysis procedure; Dimensions; Discrimination; Disease; Dual-Energy X-Ray Absorptiometry; End stage renal failure; Fracture; Functional disorder; Glucocorticoids; Hip Fractures; Hormones; Hyperparathyroidism; Image; Imaging Techniques; In Vitro; Individual; Intervention; Kidney Diseases; Kidney Failure; Kidney Transplantation; Lead; Living Donors; Magnetic Resonance Imaging; Measures; Metabolic Bone Diseases; Metabolism; Minerals; Multivariate Analysis; Normal Range; Parathyroid gland; Patients; Population; Porosity; Property; Receiver Operating Characteristics; Recovery; Relative (related person); Renal Osteodystrophy; Renal function; Research Personnel; Resolution; Risk; Schedule; Sclerosis; Sensitivity and Specificity; Solutions; Spinal Fractures; Structure; Therapeutic immunosuppression; Thick; Time; Transplant Recipients; Transplantation; Vitamin D; bone; bone loss; bone mass; bone strength; bone turnover; digital; high risk; improved; inorganic phosphate; kidney allograft; muscle strength; programs; restoration; sex; skeletal; spine bone structure; substantia spongiosa; tibia; young adult

DESCRIPTION (provided by applicant): Renal osteodystrophy (ROD) is a universal disorder in end-stage renal disease (ESRD). Abnormal parathyroid hormone (PTH) secretion and mineral metabolism result in trabecular sclerosis, cortical thinning, and increased cortical porosity. Fracture rates in dialysis patients are markedly increased, and increase further following renal transplantation. The vast majority of studies of changes in bone mass following transplantation relied on DXA estimates of bone mineral density (BMD); however, DXA BMD does not distinguish between opposing disease effects on trabecular and cortical bone and does not predict fractures in dialysis patients. Quantitative CT (QCT) provides 3D measures of cortical BMD and bone dimensions (periosteal & endosteal circumferences) and bone strength is reliably estimated. Micro-MRI provides measures of trabecular microarchitecure and connectivity. The proposed study will examine tibia trabecular architecture using (MRI, and cortical BMD and dimensions using QCT in 60 young adults at the time of renal transplantation, and over the subsequent 12 months. We hypothesize that (1) cortical BMD and dimensions will be decreased and trabecular bone volume/total volume (BV/TV) will be increased relative to age and sex at the time of transplantation, (2) cortical BMD will increase after transplantation; however, cortical thickness, cross-sectional area and endosteal dimensions will not improve, (3) trabecular thickness and BV/TV will decrease in the first six months due to glucocorticoid therapy; (4) trabecular network connectivity will not recover after transplantation, and (5) QCT measures of cortical bone density and dimensions and (MRI estimates of trabecular connectivity will predict vertebral deformities and fractures. Multivariate analyses will address the effects of PTH levels, bone turnover, muscle strength, glucocorticoid therapy and renal allograft function on changes in bone structure. Secondary analyses will assess the diagnostic test characteristics of DXA, QCT and (MRI for fracture discrimination in ESRD. Bone histomorphometry and (CT will be used to compare QCT and (MRI measures of trabecular and cortical architecture in patients with high- and low- turnover disease, and to determine if bone turnover at baseline predicts changes in bone density and structure following transplantation. The determination of changes in bone density and structure after transplantation is necessary in order to identify appropriate interventions for this high-risk population.

描述（由申请人提供）：肾脏骨营养不良（ROD）是末期肾脏疾病（ESRD）的普遍疾病。异常的甲状旁腺激素（PTH）分泌和矿物质代谢会导致小梁硬化，皮质稀疏和皮质孔隙率增加。透析患者的断裂率明显增加，并在肾移植后进一步增加。移植后骨骼变化的绝大多数研究取决于骨矿物质密度（BMD）的DXA估计值；但是，DXA BMD不能区分对小梁和皮质骨的相反疾病影响，也不能预测透析患者的骨折。定量CT（QCT）提供了3D皮质BMD和骨骼尺寸（骨膜和内骨圆周）的量度，并且可靠地估计骨强度。 Micro-MRI提供了小梁微体系环和连通性的度量。 The proposed study will examine tibia trabecular architecture using (MRI, and cortical BMD and dimensions using QCT in 60 young adults at the time of renal transplantation, and over the subsequent 12 months. We hypothesize that (1) cortical BMD and dimensions will be decreased and trabecular bone volume/total volume (BV/TV) will be increased relative to age and sex at the time of transplantation, (2)但是，皮层BMD将在移植后增加；（3）由于糖皮质激素治疗（4）小梁网络连接在移植和（5）QCT骨骼的decort bore（5）QCT bone（5）QCT bone（5）QCT骨骼，因此，皮质厚度，横截面区域和内柱尺寸不会改善。小梁连通性将预测椎骨畸形和断裂分析。次要分析将评估DXA，QCT和（MRI ESRD。骨骼组织形态计量学骨折裂缝的MRI和（CT将用于比较QCT和（MRI的小梁和皮质结构的MRI测量，在骨骼转换率是否在骨骼上进行了变化，并在骨骼的转变中进行了变化。需要在移植后的密度和结构，以确定针对此高风险人群的适当干预措施。