METABOLIC
Impact of Calcineurin Inhibitors on Bone Metabolism in Primary
Kidney Transplant Patients
G. Bozkaya, A. Nart, A. Uslu, T. Önman, A. Aykas, M. Dog ˘ an, and B. Karaca
ABSTRACT
Objective. Posttransplant bone disease and bone metabolism markers were investigated
in primary kidney transplant recipients receiving calcineurin inhibitor (CNI) based triple
immunosuppression. We examined the safety profile and independent potential of CNIs
on bone formation and bone resorption. The study also attempted to correct for modifiable
and nonmodifiable factors that impact on posttransplantation bone metabolism, such as
age, renal function, rejection, steroid dosage, and secondary hyperparathyroidism.
Materials and methods. Serum alkaline phosphatase and osteocalcin were used as
indices of bone formation and urinary deoxypyridinoline as a marker for bone resorption.
Bone mineral density (BMD) data were assessed in all patients. Osteocalcin and
deoxypyridinoline data were correlated with BMD scores to predict the clinical utility and
sensitivity of these tests. Sixty-six patients among 300 kidney transplant recipients were
enrolled as eligible candidates based upon more than 12 months’ posttransplantation
follow-up excellent graft function (GFR values 60 mL/min), and intact parathormone
levels 100 pg/mL.
Results. Mean follow-up was 1395.3 179.3 days and 1488.9 225.1 days for
cyclosporine (CsA) and FK506 groups, respectively. Mean values for alkaline phosphatase
and osteocalcin were 108.8 6.0 versus 98.4 9.7 U/L and 10.1 1.2 versus 9.8 1.5
ng/mL for the CsA and FK506 groups, respectively. Both CsA and FK506 caused mild
osteoblastic proliferation and matrix mineralization activity, as reflected by increased
osteocalcin and alkaline phosphatase levels in 22.6% and 12.5% of patients, respectively.
This bone formation activity was counterbalanced by a three-fold increase in urine
deoxypyridinoline levels in both groups. Mean deoxypyridinoline levels were, respectively,
13.8 4.4 versus 11.3 2.1 nM/mMCr in the CsA and FK506 groups. Thirty-four (68%)
patients in the CsA and 10 (62.5%) in the FK506 groups had elevated deoxypyridinoline
levels. A strong correlation existed between deoxypyridinoline levels and BMD scores for
From Izmir Teaching and Research Hospital Organ Transplan-
tation Center and Izmir Teaching and Research Hospital Depart-
ment of Biochemistry, Izmir, Turkey.
Address reprint requests to Ahmet Nart, MD, Izmir Egitim ve
Aras ¸ tırma Hastanesi Organ Nakli Aras ¸ tırma Hastanesi Bozyaka,
35290, Izmir, Turkey. Email: ahmetnart@yahoo.com
© 2008 by Elsevier Inc. All rights reserved. 0041-1345/08/$–see front matter
360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2007.11.040
Transplantation Proceedings, 40, 151–155 (2008) 151