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.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Skeletal Biology Development and Disease Study Section (SBDD)
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Kimmel, Paul
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Children's Hospital of Philadelphia
United States
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Rajapakse, Chamith S; Leonard, Mary B; Bhagat, Yusuf A et al. (2012) Micro-MR imaging-based computational biomechanics demonstrates reduction in cortical and trabecular bone strength after renal transplantation. Radiology 262:912-20
Bhagat, Yusuf A; Rajapakse, Chamith S; Magland, Jeremy F et al. (2011) Performance of ?MRI-Based virtual bone biopsy for structural and mechanical analysis at the distal tibia at 7T field strength. J Magn Reson Imaging 33:372-81
Bhagat, Yusuf A; Rajapakse, Chamith S; Magland, Jeremy F et al. (2011) On the significance of motion degradation in high-resolution 3D ?MRI of trabecular bone. Acad Radiol 18:1205-16