title: 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.
authors: Department of Medicine, Kaiser Permanente Medical Center, Oakland, California;
authors: Sapna P
authors: SP
authors: Iyer
authors: Department of Orthopedics and Rehabilitation, University of Rochester Medical Center, Rochester, New York;
authors: Lucas E
authors: LE
authors: Nikkel
authors: Department of Medicine and.
authors: Kyle K
authors: KK
authors: Nishiyama
authors: Department of Medicine and.
authors: Elzbieta
authors: E
authors: Dworakowski
authors: Department of Medicine and.
authors: Serge
authors: S
authors: Cremers
authors: Department of Medicine and.
authors: Chiyuan
authors: C
authors: Zhang
authors: Department of Medicine and.
authors: Donald J
authors: DJ
authors: McMahon
authors: Institut National de la Santé et de la Recherche Médicale U1033, University of Lyon, Lyon, France;
authors: Stephanie
authors: S
authors: Boutroy
authors: McKay Orthopaedic Research Laboratory, Department of Orthopedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and.
authors: X Sherry
authors: XS
authors: Liu
authors: Department of Surgery, Columbia University Medical Center, New York, New York;
authors: Lloyd E
authors: LE
authors: Ratner
authors: Department of Medicine and.
authors: David J
authors: DJ
authors: Cohen
authors: School of Engineering, Department of Biomedical Engineering, Columbia University, New York, New York.
authors: X Edward
authors: XE
authors: Guo
authors: Department of Medicine and.
authors: Elizabeth
authors: E
authors: Shane
authors: Department of Medicine and tln2001@columbia.edu.
authors: Thomas L
authors: TL
authors: Nickolas
mesh_terms: D000328:Adult; D015519:Bone Density / Q000187:drug effects; D001847:Bone Diseases / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000453:epidemiology; D016723:Bone Remodeling / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects; D006084:Graft Rejection / Q000188:drug therapy*; D006620:Hip Fractures / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000453:epidemiology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000601:surgery*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000706:statistics & numerical data; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011859:Radiography; D012307:Risk Factors; D013375:Substance Withdrawal Syndrome
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone