Changes in Skeletal Microarchitecture Following Renal Transplantation

Renal osteodystrophy (ROD) is a multifactorial and universal disorder in chronic kidney disease (CKD). 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 following renal transplantation. The vast majority of studies of bone mass in CKD have relied on dual energy x-ray absorptiometry (DXA) measures of bone mineral density (BMD); however, DXA does not distinguish between opposing disease effects on trabecular and cortical bone. Quantitative computed tomography (QCT) provides 3D measures of cortical volumetric BMD and bone dimensions (periosteal and endosteal circumferences) and bone strength can be estimated. Micro magnetic resonance imaging (IJ-MRI) provides measures of trabecular structure. The proposed study will examine trabecular bone volume (BVITV) and micro-architecture using IJ-MRI, and cortical volumetric BMD and dimensions using QCT in 60 healthy adult controls and 60 end-stage renal disease patients (ages 21-44 yr) at the time of renal transplantation. The studies will be repeated at 6 and 12 months following transplantation. Bone biopsies will be obtained for histomorphometry and IJ-CT at the time of transplantation in 30 subjects undergoing living-donor transplantation. The hypotheses are that (a) cortical volumetric BMD and dimensions are significantly decreased at the time of transplantation, (b) trabecular BVITV is correlated with PTH levels at the time of transplantation, and (c) changes in cortical and trabecular bone parameters are associated with PTH levels, bone turnover, muscle strength, glucocorticoid therapy and renal function following transplantation. Secondary analyses will compare DXA, QCT and IJ-MRI in the assessment of bone structure in order to demonstrate that the structural effects of ROD on cortical and trabecular bone are poorly captured by DXA. Bone histomorphometry and IJ-CT will be used to compare QCT and IJ-MRI measures of trabecular and cortical architecture in patients with high-turnover and low turnover disease, and to determine if bone turnover at baseline predicts changes in cortical and trabecular architecture following transplantation. The determination of skeletal micro-architecture is necessary in order to identify appropriate interventions to improve bone strength following renal transplantation.