Pamidronate therapy as prevention of bone loss following renal transplantation

Background. Very rapid bone loss, osteopenia and skeletal morbidity after r enal transplantation have been well documented and found to occur in a sex dependent fashion. Glucocorticoids, cyclosporine and pre-existing uremic os teodystrophy have been implicated in the pathogenesis of the skeletal lesio ns. Glucocorticoid induced osteopenia is also a serious clinical problem in patients with various nonrenal diseases and can be prevented, or at least attenuated, by pamidronate and other bisphosphonates. Method. We prospectively studied 26 male patients undergoing renal transpla ntation, and randomized them to receive either placebo or intravenous pamid ronate: (0.5 mg/kg) at the time of transplantation and again one month late r. All patients received immunosuppression comprising prednisolone, cyclosp orine and azathioprine. The bone mineral density (BMD) of the second, third and fourth lumbar vertebrae and of the femoral neck was measured at the ti me of transplantation and at three months and 12 months after transplantati on using dual energy X-ray absorptiometry (DXA). Results. Twelve months after transplantation, the mean (+/- SEM) BMD of the lumbar vertebrae in patients who received placebo had decreased 6.4% (P < 0.05). In contrast, patients who received pamidronate experienced no signif icant reduction of BMD at the lumbar vertebrae. At the femoral neck, placeb o-treated patients showed a reduction of BMD of 9% (P < 0.005), whereas the re was no significant change in the pamidronate treated group. The two stud y groups had similar patient profiles, serum parathyroid hormone (PTH) and aluminium concentrations. After transplantation, comparable falls in the se rum creatinine and PTH concentration were found in the two groups. Apart fr om transient hypocalcemia in two patients, no significant adverse effects o f pamidronate were noted. Conclusion. This study has shown that the early rapid bone loss that occurs in men during the first 12 months after renal transplantation can be preve nted by two intravenous doses of pamidronate given at transplantation and o ne month later. The regimen was simple to administer, well tolerated and po tentially applicable to other clinical groups of glucocorticoid treatment p atients.