Long-term effects on bone mineral density of pamidronate given at the time of renal transplantation

Background. Fracture rate after renal transplantation is substantially increased, is a source of morbidity and mortality, and correlates with osteopenia. The rate of bone loss after transplantation is time dependent. While we recorded marked bone loss during the first year after renal transplantation, bone loss in long-term recipients (>24 months) was found to be similar to expected age-related decline. We have previously shown that treatment with pamidronate at the time of transplantation protected the skeleton over a 1-year study period. Methods. We have reexamined patients who participated in our original study, all of whom had been randomized to receive either placebo or pamidronate (0.5 mg/kg) at the time of transplantation and 1 month later. We now report 4-year data from 17 of the 26 original cohort. All patients received immunosuppression, comprising prednisolone, cyclosporine, and azathioprine. Results. We found that without prophylaxis bone loss at 4 years was substantial and significant at the femoral neck (mean loss was -12.3%) but was not significant at the lumbar spine (mean loss was -4.64%). Patients who received two doses of pamidronate experienced no statistically significant bone loss at either the femoral neck or the lumbar spine. Patient characteristics of the placebo and treatment groups were similar with the exception of serum parathyroid hormone concentrations, which remained higher at 4 years in the pamidronate-treated patients (15.8+/-3.7 pmol/L vs. 9.8+/-1.8 pmol/L, P<0.05). Conclusion. Without prophylaxis, most patients who continue to receive low dose glucocorticoids as part of maintenance immunosuppression manifest a substantial deficit in bone mineral density (BMD) at the femoral neck. In contrast, two doses of pamidronate given at the time of transplantation and 1 month later protected the skeleton from significant bone loss over the 4 years after transplantation.