Kidney transplantation with early corticosteroid withdrawal: paradoxical effects at the central and peripheral skeleton.

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), high-resolution 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.

Pancreas-kidney transplantation is associated with reduced fracture risk compared with kidney-alone transplantation in men with type 1 diabetes.

Both type 1 diabetes mellitus and end-stage renal disease are associated with increased fracture risk, likely because of 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 and 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 4933 had a simultaneous pancreas-kidney transplant and 6212 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 with 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.