Fan S L, Almond M K, Ball E, Evans K, Cunningham J
Department of Renal Medicine and Transplantation, The Royal London Hospital, London, England, United Kingdom.
Kidney Int. 2000 Feb;57(2):684-90. doi: 10.1046/j.1523-1755.2000.00890.x.
Very rapid bone loss, osteopenia and skeletal morbidity after renal transplantation have been well documented and found to occur in a sex dependent fashion. Glucocorticoids, cyclosporine and pre-existing uremic osteodystrophy have been implicated in the pathogenesis of the skeletal lesions. 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.
We prospectively studied 26 male patients undergoing renal transplantation, and randomized them to receive either placebo or intravenous pamidronate (0.5 mg/kg) at the time of transplantation and again one month later. All patients received immunosuppression comprising prednisolone, cyclosporine and azathioprine. The bone mineral density (BMD) of the second, third and fourth lumbar vertebrae and of the femoral neck was measured at the time of transplantation and at three months and 12 months after transplantation using dual energy X-ray absorptiometry (DXA).
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 significant reduction of BMD at the lumbar vertebrae. At the femoral neck, placebo-treated patients showed a reduction of BMD of 9% (P < 0.005), whereas there was no significant change in the pamidronate treated group. The two study groups had similar patient profiles, serum parathyroid hormone (PTH) and aluminium concentrations. After transplantation, comparable falls in the serum creatinine and PTH concentration were found in the two groups. Apart from transient hypocalcemia in two patients, no significant adverse effects of pamidronate were noted.
This study has shown that the early rapid bone loss that occurs in men during the first 12 months after renal transplantation can be prevented by two intravenous doses of pamidronate given at transplantation and one month later. The regimen was simple to administer, well tolerated and potentially applicable to other clinical groups of glucocorticoid treatment patients.
肾移植后出现的极快速骨质流失、骨质减少和骨骼病变已有充分记录，且发现其发生存在性别差异。糖皮质激素、环孢素和既往存在的尿毒症性骨营养不良与骨骼病变的发病机制有关。糖皮质激素诱导的骨质减少在患有各种非肾脏疾病的患者中也是一个严重的临床问题，帕米膦酸盐和其他双膦酸盐可以预防或至少减轻这种情况。
我们对26名接受肾移植的男性患者进行了前瞻性研究，并将他们随机分为两组，一组在移植时及移植后1个月接受安慰剂，另一组接受静脉注射帕米膦酸盐（0.5mg/kg）。所有患者均接受包括泼尼松龙、环孢素和硫唑嘌呤的免疫抑制治疗。在移植时以及移植后3个月和12个月，使用双能X线吸收法（DXA）测量第二、第三和第四腰椎以及股骨颈的骨密度（BMD）。
移植后12个月，接受安慰剂的患者腰椎平均（±SEM）骨密度下降了6.4%（P<0.05）。相比之下，接受帕米膦酸盐治疗的患者腰椎骨密度没有显著降低。在股骨颈，接受安慰剂治疗的患者骨密度下降了9%（P<0.005），而帕米膦酸盐治疗组没有显著变化。两个研究组的患者特征、血清甲状旁腺激素（PTH）和铝浓度相似。移植后，两组患者的血清肌酐和PTH浓度下降程度相当。除了两名患者出现短暂低钙血症外，未观察到帕米膦酸盐的明显不良反应。
本研究表明，肾移植后男性在最初12个月内发生的早期快速骨质流失可以通过在移植时及移植后1个月静脉注射两次帕米膦酸盐来预防。该方案给药简单，耐受性良好，可能适用于其他接受糖皮质激素治疗的临床群体。
