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

Abstract

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.

Figure 1.

Flow-chart of patients who enrolled, dropped out, and completed the study.

Figure 2.

Twelve-month changes in areal BMD (aBMD) measured by DXA at the central and peripheral skeleton. Data is represented as change±SEM in aBMD for patients on ECSW at the: (A) lumbar spine, (B) hip, and (C) forearm. *P<0.05.

Figure 3.

Twelve-month changes in radius cortical and trabecular measures obtained by HRpQCT. Data is represented as change±SEM in radius: (A) cortical (Ct) and trabecular (Tb) area, (B) cortical density (Ct Density) and thickness (Ct Th), and (C) trabecular density (Tb Density) and number (Tb N). *P<0.05.

Figure 4.

Scatter plots representing relationships between time-averaged post-transplantation PTH and 12-month changes in: (A) radius cortical area and (B) thickness. Horizontal reference line demarcates the lack of bone loss based on our laboratory’s precision for each bone structural parameter.

Figure 5.

Twelve-month decreases in trabecular density and whole bone stiffness stratified by level of PTH. The effect of time-averaged post-transplantation PTH levels between 100 and 140 pg/ml compared with <100 and >140 pg/ml on 12-month change in (A) radius trabecular density and (B) whole-bone stiffness. Comparison with baseline: *P<0.001. Comparison between groups: ^ŧP<0.05; ^χP<0.001.