Corticosteroid, Parathyroid Hormone, and Body Composition Associations With Bone Density and Structure Following Kidney Transplantation.

RATIONALE &

objectiveKidney transplant (KT) ameliorates the underlying abnormalities contributing to skeletal fragility in chronic kidney disease, but fracture rates increase after transplant. This study sought to assess the impact of changes in body composition and mineral metabolism on bone mineral density (BMD) and structure following kidney KT. STUDY

design24-month prospective cohort study. SETTING &

participants60 incident KT recipients and 361 healthy controls aged 20-60 years. OUTCOMES: Tibia volumetric BMD (vBMD) and cortical dimensions measured using peripheral quantitative computed tomography and areal BMD (aBMD), appendicular lean mass index (ALMI), and fat mass index measured using dual-energy X-ray absorptiometry. ANALYTICAL APPROACH: Analytical Approach: Outcomes were converted to sex-specific z scores for age and compared with those in 361 controls. Quasi-least-squares regression models identified correlates of change.

resultsAt baseline, ALMI, trabecular and cortical vBMD, cortical thickness, and total hip, femoral neck, and ultradistal radius aBMD were lower in KT recipients versus controls (P ≤ 0.003). During the first 6 months after KT, ALMI, fat mass index, and body mass index (BMI) increased (P < 0.001), whereas tibia trabecular vBMD and lumbar spine aBMD decreased (P ≤ 0.005). Cortical vBMD increased from 6 months onward (P < 0.001) in association with decreasing parathyroid hormone levels (P = 0.004). Cortical thickness decreased between 6 and 24 months (P = 0.002) because of a loss of endocortical bone. Total hip and femoral neck aBMD remained stable for 6 months, then improved through 24 months (P ≤ 0.02). Ultradistal radius aBMD decreased throughout the study (P ≤ 0.003). Higher BMI and ALMI were associated with gains in hip and spine aBMD and trabecular vBMD (all P ≤ 0.02). Corticosteroid dose was negatively associated with changes in spine and hip aBMD and cortical and trabecular vBMD (all P ≤ 0.02). Higher bone turnover marker levels and loss of cortical vBMD and thickness were associated with increases in serum calcium concentrations (P ≤ 0.03). LIMITATIONS: Not generalizable to older KT recipients.

conclusionsSkeletal deficits in KT recipients largely stabilize or improve beyond 6 months, with the exception of progressive cortical thinning. Strategies are needed to preserve cortical bone before and after KT. Gains in BMI and ALMI may improve bone health in the weight-bearing skeleton following KT. PLAIN-LANGUAGE SUMMARY: We enrolled 60 adults at the time of kidney transplant (KT) and compared measures of bone and muscle mass versus those in 361 healthy individuals. At the time of transplant, KT recipients had low muscle mass, low bone density, and thin bones compared with healthy individuals. After transplant, KT recipients rapidly gained muscle and fat. Despite the adverse effect of corticosteroid medications on bone, hip bone density improved significantly between 6 and 24 months. More muscle was associated with greater gains in hip and spine bone density over 2 years. In contrast, long bones got progressively thinner in association with biomarkers of bone breakdown. This study improves our understanding of the contributions of corticosteroids, muscle, and mineral metabolism on changes in bone density and thickness after KT, as well as the potential for recovery of bone density at selected skeletal sites.