The use of early corticosteroid withdrawal (ECSW) protocols after kidney transplantation has become common, but the effects on fracture risk and bone quality are unclear. We enrolled 47 first-time adult transplant recipients managed with ECSW into a 1-year study to evaluate changes in bone mass, microarchitecture, biomechanical competence, and remodeling with dual energy x-ray absorptiometry (DXA), highresolution peripheral quantitative computed tomography (HRpQCT), parathyroid hormone (PTH) levels, and bone turnover markers obtained at baseline and 3, 6, and 12 months post-transplantation. Compared with baseline, 12-month areal bone mineral density by DXA did not change significantly at the spine and hip, but it declined significantly at the 1/3 and ultradistal radii (2.2% and 2.9%, respectively; both P,0.001). HRpQCT of the distal radius revealed declines in cortical area, density, and thickness (3.9%, 2.1%, and 3.1%, respectively; all P,0.001), trabecular density (4.4%; P,0.001), and stiffness and failure load (3.1% and 3.5%, respectively; both P,0.05). Findings were similar at the tibia. Increasing severity of hyperparathyroidism was associated with increased cortical losses. However, loss of trabecular bone and bone strength were most severe at the lowest and highest PTH levels. In summary, ECSW was associated with preservation of bone mineral density at the central skeleton; however, it was also associated with progressive declines in cortical and trabecular bone density at the peripheral skeleton. Cortical decreases related directly to PTH levels, whereas the relationship between PTH and trabecular bone decreases was bimodal. Studies are needed to determine whether pharmacologic agents that suppress PTH will prevent cortical and trabecular losses and post-transplant fractures.
Patients with chronic kidney disease (CKD) who undergo kidney transplantation experience bone loss and increased risk of fracture. However, the mechanisms of this bone loss are unclear. Our objective was to use image registration to define the cortex to assess changes in cortical porosity (Ct.Po) in patients undergoing first-time kidney transplantation. We obtained serial measurements of parathyroid hormone (PTH) and bone turnover markers and used high-resolution peripheral quantitative computed tomography (HRpQCT) to scan the distal radius and tibia in 31 patients (21 men, 10 women; aged 51.9 AE 13.4 years) at transplant and after 1 year. Baseline and 1-year images were aligned using a fully automated, intensity-based image registration framework. We compared three methods to define the cortical region of interest (ROI) and quantify the changes: 1) cortical bone was independently defined in baseline and follow-up scans; 2) cortical bone was defined as the common cortical ROI; and 3) the cortical ROI at baseline was carried forward to 1-year follow-up (baseline-indexed). By the independently defined ROI, Ct.Po increased 11.7% at the radius and 9.1% at the tibia, whereas by the common ROI, Ct.Po increased 14.6% at the radius and 9.1% at the tibia. By the baseline-indexed ROI, which provides insight into changes at the endocortical region, Ct.Po increased 63.4% at the radius and 17.6% at the tibia. We found significant relationships between changes in Ct.Po and bone formation and resorption markers at the radius. The strongest associations were found between markers and Ct.Po using the baseline-index method. We conclude that Ct.Po increases throughout the cortex after kidney transplant, and this increase is particularly marked at the endocortical surface. These methods may prove useful for all HR-pQCT longitudinal studies, particularly when changes are expected at the endocortical region.
Trabecular bone score may be a useful method to assess and monitor bone quality and strength and classify fracture risk in kidney transplant recipients.
Both type 1 diabetes mellitus and end stage renal disease are associated with increased fracture risk, likely due to metabolic abnormalities that reduce bone strength. Simultaneous pancreas-kidney transplantation is a treatment of choice for patients with both disorders, yet the effects of simultaneous pancreas-kidney versus kidney transplantation alone on post-transplantation fracture risk are unknown. From the United States Renal Data System we identified 11, 145 adults with type 1 diabetes undergoing transplantation of whom 4,933 had a simultaneous pancreas-kidney while 6, 212 had a kidney alone transplant between 2000 and 2006. Post-transplantation fractures resulting in hospitalization were identified from discharge codes. Time to first fracture was modeled and propensity score adjustment was used to balance covariates between groups. Fractures occurred in significantly fewer (4.7%) of pancreas-kidney compared to kidney-alone transplant (5.9%) cohorts. After gender stratification and adjustment for fracture covariates, pancreas-kidney transplantation was associated with a significant 31% reduction in fracture risk in men (hazard risk 0.69). Older age, white race, prior dialysis and pre transplantation fracture were also associated with increased fracture risk. Prospective studies are needed to determine the gender-specific mechanisms by which pancreas-kidney transplantation reduces fracture risk in men.
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