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

J Am Soc Nephrol. 2014 Jun;25(6):1331-41. doi: 10.1681/ASN.2013080851. Epub 2014 Feb 7.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bone Density / drug effects
  • Bone Diseases / chemically induced*
  • Bone Diseases / diagnostic imaging
  • Bone Diseases / epidemiology
  • Bone Remodeling / drug effects
  • Dexamethasone / administration & dosage
  • Dexamethasone / adverse effects*
  • Female
  • Follow-Up Studies
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / adverse effects
  • Graft Rejection / drug therapy*
  • Hip Fractures / chemically induced*
  • Hip Fractures / diagnostic imaging
  • Hip Fractures / epidemiology
  • Humans
  • Kidney Failure, Chronic / epidemiology
  • Kidney Failure, Chronic / surgery*
  • Kidney Transplantation / adverse effects*
  • Kidney Transplantation / statistics & numerical data
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Radiography
  • Risk Factors
  • Substance Withdrawal Syndrome

Substances

  • Glucocorticoids
  • Dexamethasone