CHANGES IN SKELETAL MICROARCHITECTURE FOLLOWING RENAL TRANSPLANTATION

描述（由申请人提供）：肾性骨营养不良（ROD）是终末期肾病（ESRD）的一种普遍疾病。异常甲状旁腺激素（PTH）分泌和矿物质代谢导致小梁硬化、皮质变薄和皮质孔隙增加。透析患者骨折率明显增加，肾移植后进一步增加。绝大多数关于移植后骨量变化的研究依赖于DXA对骨矿物质密度（BMD）的估计；然而，DXA BMD不能区分疾病对小梁骨和皮质骨的相反影响，也不能预测透析患者的骨折。定量CT （QCT）提供皮质骨密度和骨尺寸（骨膜和内膜周长）的三维测量，并可靠地估计骨强度。显微mri提供了小梁微结构和连通性的测量。本研究将对60名年轻成人在肾移植时及随后的12个月内的胫骨小梁结构、皮质骨密度和尺寸进行MRI检查。我们假设(1)皮质骨密度和尺寸在移植时相对于年龄和性别会降低，骨小梁体积/总体积（BV/TV）会增加；(2)移植后皮质骨密度会增加；然而，皮质厚度、横截面积和内膜尺寸并没有改善；(3)在前6个月糖皮质激素治疗会降低小梁厚度和BV/TV；(4)移植后小梁网络连通性不会恢复，(5)皮质骨密度和尺寸的QCT测量以及小梁连通性的MRI估计将预测椎体畸形和骨折。多变量分析将探讨甲状旁腺激素水平、骨转换、肌肉力量、糖皮质激素治疗和同种异体肾移植功能对骨结构变化的影响。二次分析将评估DXA、QCT和MRI对ESRD骨折鉴别的诊断试验特征。骨组织形态测量和CT将用于比较高、低转换疾病患者的骨小梁和皮质结构的QCT和MRI测量，并确定基线骨转换是否预测移植后骨密度和结构的变化。确定移植后骨密度和结构的变化是必要的，以便为这一高危人群确定适当的干预措施。

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.