Parameters of high bone-turnover predict bone loss in renal transplant patients: a longitudinal study.
BACKGROUND
Osteoporosis is a serious complication of kidney transplantation. Various factors have been postulated to contribute to posttransplant bone loss, among them treatment with corticosteroids, the use of cyclosporine and cyclosporine-like agents, and persistent hyperparathyroidism. In a previous cross-sectional study of long-term renal transplant recipients, we observed that osteoporosis or osteopenia was present in 88% of patients. Because biochemical markers of bone formation (serum osteocalcin) and bone resorption (urine pyridinoline, PYD, and deoxypyridinoline, DPD) were elevated in the majority of study subjects, we hypothesized that elevated rates of bone-turnover contribute to posttransplant bone loss in long-term renal transplant patients. This study was performed to examine this hypothesis.


METHODS
The study population was composed of 62 patients who were more than 1-year postrenal transplantation and who had preserved renal function. They were followed prospectively for 1 year. Biochemical markers of bone-turnover were measured at study entry, and patients were classified as having high bone-turnover based on elevated urinary levels of at least one marker of bone resorption (i.e., PYD or DPD) and/or serum osteocalcin (group 1). If none of these were present, they were classified as having normal bone-turnover (group 2). Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (DEXA) at time of entry into the study and again after 1 year of follow-up. The changes in BMD at the lumbar spine, hip, and wrist over the period of the study were compared between the high and normal bone-turnover groups.


RESULTS
Forty-three patients (69%) were classified as having high bone-turnover (Group 1), and 19 patients (31%) were classified as having normal bone-turnover (Group 2). There was a statistically significant difference in change in BMD between the two groups at the lumbar spine (-1.11+/-0.42%, high bone-turnover, vs. 0.64+/-0.54%, normal bone-turnover; P=0.02) and the hip (-0.69+/-0.38%, high bone-turnover, vs. 1.36+/-0.66%, normal bone-turnover; P=0.006). Whereas group 2 had stable bone mass, group 1 exhibited bone loss at these skeletal sites.


CONCLUSIONS
Our results indicate that bone loss is greater in renal transplant recipients with elevated biochemical markers of bone-turnover, suggesting that these markers may be useful in identifying patients at risk for continued bone loss. These data support the hypothesis that continued bone loss in long-term renal transplant recipients is associated with high bone-turnover. If accelerated bone resorption does play a role in posttransplant bone loss, this would provide a strong rationale for use of antiresorptive therapy for the prevention and treatment of this complication.
Cruz
D N
DN
Department of Surgery, Yale University School of Medicine, New Haven, CT 06520-8029, USA.
Wysolmerski
J J
JJ
Brickel
H M
HM
Gundberg
C G
CG
Simpson
C A
CA
Mitnick
M A
MA
Kliger
A S
AS
Lorber
M I
MI
Basadonna
G P
GP
Friedman
A L
AL
Insogna
K L
KL
Bia
M J
MJ
D000596:Amino Acids / Q000652:urine; D015415:Biomarkers; D015519:Bone Density; D016723:Bone Remodeling; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin; D010024:Osteoporosis / Q000209:etiology*; D010281:Parathyroid Hormone / Q000097:blood; D011379:Prognosis; D011446:Prospective Studies
D000596:Amino Acids; D015415:Biomarkers; D010281:Parathyroid Hormone; D015675:Osteocalcin; C015484:pyridinoline; C036020:deoxypyridinoline