Effect of 1,25-dihydroxyvitamin D3 and calcium carbonate on bone loss associated with long-term renal transplantation.

To investigate the effect of calcitriol plus calcium carbonate on the bone loss associated with long-term renal transplantation, 30 patients with serum creatinine levels less than 2.0 mg/dL were randomly allocated to a control (n = 14) or treatment group (n = 16) and studied with bone biopsy and densitometry at baseline and after 1 year of follow-up. Calcitriol (0.25 microg/d) plus calcium carbonate (500 mg/d of elemental calcium) were administered to patients in the treatment group. Comparing the baseline and final data of each group at a time, no change in bone mineral density (BMD) z score was observed at the distal radius (control, -0.8 +/- 0.8 versus -0.6 +/- 0.9; treatment, -1.0 +/- 1.0 versus -1.0 +/- 1.1). However, a significant increase (P < 0.05) was found at the lumbar spine in both groups (control, 0.1 +/- 1.6 versus 0.4 +/- 1.6; treatment, -0.1 +/- 1.5 versus 0.3 +/- 1.5) and only in the treatment group at the femoral neck (control, -0.9 +/- 1.0 versus -0.8 +/- 1.0; treatment, -0.5 +/- 0.9 versus -0.3 +/- 1.1). When BMD was compared between groups, no significant differences were observed at the evaluated anatomic sites at baseline or after 1 year of follow-up. After 1 year of follow-up, adjusting for age and sex (z score), the control group showed a trend to reduce the value of several histomorphometric parameters, including osteoblast surface (-2.2 +/- 6.1 versus -3.4 +/- 3.9), osteoid surface (-2.3 +/- 3.5 versus -3.1 +/- 3.9), and osteoclast surface (0.2 +/- 5.0 versus -1.3 +/- 3.3). Consequently, there was a significant reduction (P < 0.05) in mineralizing surface (-9.8 +/- 11.0 versus -15.8 +/- 12.3) and appositional rate (-5.8 +/- 2.7 versus -7.6 +/- 2.2). In the treatment group, a significant reduction (P < 0.05) in osteoclast surface was observed at the end of the study (3.9 +/- 6.8 versus -1.2 +/- 4.1), and although a trend to reduce osteoblast surface (-2.5 +/- 2.6 versus -3.2 +/- 5.7) and osteoid surface (-2.1 +/- 2.5 versus -3.2 +/- 2.8) was also found, patients maintained approximately the same level of wall thickness (-5.2 +/- 5.3 versus -5.3 +/- 3.3) and bone volume (-2.7 +/- 1.8 versus -2.5 +/- 1.7). However, there was no improvement in mineralizing surface (-4.2 +/- 2.9 versus -10.4 +/- 3.6) or appositional rate (-5.8 +/- 3.1 versus -8.1 +/- 2.6). No significant differences in bone histomorphometric variables were observed between groups after 1 year of follow-up. In conclusion, 1,25-dihydroxyvitamin D3 and calcium carbonate did not significantly improve bone loss in long-term renal transplant recipients. However, significant osteoclast suppression and a trend to maintain trabecular bone volume and wall thickness as well as improve the axial BMD were observed in the treatment group.

Bone loss in long-term renal transplantation: histopathology and densitometry analysis.

BACKGROUND: There is little information of the spectrum and factors implicated in the bone loss in long-term renal transplantation, and virtually no data using both histomorphometric and densitometric analysis. METHODS: Twenty-three males and 22 females (13 postmenopausal) were studied with a bone biopsy and densitometry. Sixteen patients were on cyclosporine A monotherapy, 20 on azathioprine + prednisolone, and 9 on cyclosporine A + prednisolone or triple therapy. The mean time after transplantation was 127 +/- 70 months. RESULTS: No group had a significant decrease in bone mineral density (BMD) of the axial skeleton compared with an age- and sex-matched normal population. Compared with sex-matched young controls, osteopenia was observed in all groups at the femoral neck (except premenopausal women and triple therapy) and in the triple-therapy group at the L1-L4 spine region. At the distal radius, osteopenia was found in all the groups. Histopathological diagnosis was mixed uremic osteodystrophy in 46.5%, adynamic bone in 23.2%, hyperparathyroid disease in 13.9%, and normal bone in 16.3%. The diagnosis was not different according to immunosuppressive therapy, but men tended to show more mixed uremic bone disease. There was no significant difference in BMD between histopathological subtypes. In general, patients showed slight osteoclast function increase, osteoblast function decrease, and marked retardation of dynamic parameters. The cyclosporine A monotherapy group had a significantly lower appositional rate than azathioprine + prednisolone. Men had a significantly lower bone volume than women, and premenopausal women had a significantly lower mineralizing surface than postmenopausal women and men. In the multivariate analysis, male gender, time after transplantation, old age, and time on dialysis prior to transplantation were significant predictive factors for a negative effect on bone mass. CONCLUSIONS: Long-term renal transplant-patients showed reduced BMD in both trabecular and cortical bone. This reduction in BMD was not as severe as in short-term reports and was associated with osteoclast stimulation, osteoblast suppression, and retardation of mineral apposition and bone formation rates. Bone mass loss was not different between the immunosuppression therapy groups. Male gender and age were the strongest predictive factors for low bone mass.