Changes in bone mineral density over 18 months following kidney transplantation: the respective roles of prednisone and parathyroid hormone.
BACKGROUND
Prednisone is a major factor of bone loss after kidney transplantation. The role of hyperparathyroidism and immunosuppressors is less clear.


METHODS
Thirty-three patients (14 men, 19 women) with ESRD were followed prospectively for 18 months after kidney transplantation. All patients received prednisone and cyclosporin A (CyA) with (n=18) or without azathioprine. Rejection episodes were treated with boluses of methylprednisolone. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry for the spine, hip and whole body (total, trunk, limbs) at 1, 12, 24, 36, 60 and 75 weeks after kidney transplantation. At the same time, blood was assayed for calcium, phosphorus, intact-PTH, alkaline phosphatase, creatinine and CyA, and 24-h urine was assayed for Ca and P.


RESULTS
BMD at baseline was low at all skeletal sites in women, but not in men. BMD decreased significantly at the spine (-7.0+/-0.9%, week 24), trunk (-4.8+/-0.5%, week 24), total hip (-4.3+/-1.0%, week 36), whole body (-2.2+/-0.4%, week 36) and limbs (-1.0+/-0.7%, week 74). BMD changes over time followed three different patterns: no change or gain, continuous loss, and NADIR. For the spine and trunk, two thirds of patients had a NADIR pattern with recovery at the end of the study, and one-quarter of patients had continuous bone loss. For the limbs, BMD rose or remained stable (n=20), decreased continuously (n=8) or had a NADIR pattern (n=5). Neither gender nor time on dialysis prior to transplantation influenced BMD changes. Patients with PTH serum concentrations below the median value 1 week after kidney transplantation (109 pg/ml) had continuous bone loss at the whole body or limbs but not at other sites. The cumulative dose of prednisone correlated negatively with BMD changes at the spine (r=-0.39, P<0.03), hip (r=-0.50, P=0.005) and trunk (r=-0.52, P=0.002), but not at the whole body or limbs. CyA levels in blood did not correlate with BMD changes. BMD for the whole body and limbs did not change in the patients receiving azathioprine (n=16; -2.7+/-0.7%, P=0.013) but decreased in the others (-2.8+/-0.9%, P<0.0002).


CONCLUSIONS
High cumulative prednisone doses are deleterious for the axial skeleton. Low levels of PTH observed 1 week after kidney transplantation are predictive of continuous cortical bone loss.
Casez
Jean-Paul
JP
Department of Nephrology, University of Nice, France.
Lippuner
Kurt
K
Horber
Fritz F
FF
Montandon
André
A
Jaeger
Philippe
P
D015502:Absorptiometry, Photon; D001379:Azathioprine / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects / Q000502:physiology*; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008297:Male; D010281:Parathyroid Hormone / Q000502:physiology*; D017698:Postmenopause; D011241:Prednisone / Q000627:therapeutic use*; D017697:Premenopause; D011446:Prospective Studies; D013997:Time Factors
D007166:Immunosuppressive Agents; D010281:Parathyroid Hormone; D016572:Cyclosporine; D001379:Azathioprine; D011241:Prednisone