Coco Maria, Glicklich Daniel, Faugere Marie Claude, Burris Larry, Bognar Istvan, Durkin Peter, Tellis Vivian, Greenstein Stuart, Schechner Richard, Figueroa Katherine, McDonough Patricia, Wang Guodong, Malluche Hartmut
Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York 10467, USA.
J Am Soc Nephrol. 2003 Oct;14(10):2669-76. doi: 10.1097/01.asn.0000087092.53894.80.
Renal transplant recipients are at risk of developing bone abnormalities that result in bone loss and bone fractures. These are related to underlying renal osteodystrophy, hypophosphatemia, and immunosuppressive treatment regimen. Although bisphosphonates are useful in ameliorating bone mineral loss after transplantation, it is not known whether their use in renal transplant patients leads to excessive suppression of bone turnover and increased incidence of adynamic bone disease. A randomized, prospective, controlled, clinical trial was conducted using the bisphosphonate pamidronate intravenously in patients with new renal transplants. Treatment subjects (PAM) received pamidronate with vitamin D and calcium at baseline and at months 1, 2, 3, and 6. Control (CON) subjects received vitamin D and calcium only. During months 6 to 12, the subjects were observed without pamidronate treatment. Biochemical parameters of bone turnover were obtained monthly and, bone mineral density (BMD) was obtained at baseline and months 6 and 12. Bone biopsies for mineralized bone histology were obtained at baseline and at 6 mo in a subgroup of subjects who underwent scheduled living donor transplantation. PAM preserved bone mass at 6 and 12 mo as measured by bone densitometry and histomorphometry. CON had decreased vertebral BMD at 6 and 12 mo (4.8 +/- 0.08 and 6.1 +/- 0.09%, respectively). Biochemical parameters of bone turnover were similar in both groups at 6 and 12 mo. Bone histology revealed low turnover bone disease in 50% of the patients at baseline. At 6 mo, all of PAM had adynamic bone disease, whereas 50% of CON continued to have or developed decreased bone turnover. Pamidronate preserved vertebral BMD during treatment and 6 mo after cessation of treatment. Pamidronate treatment was associated with development of adynamic bone histology. Whether an improved BMD with adynamic bone histology is useful in maintaining long-term bone health in renal transplant recipients requires further study.
肾移植受者有发生骨异常的风险,这会导致骨质流失和骨折。这些与潜在的肾性骨营养不良、低磷血症和免疫抑制治疗方案有关。尽管双膦酸盐在改善移植后的骨矿物质流失方面有用,但在肾移植患者中使用它们是否会导致骨转换过度抑制以及动力缺失性骨病的发生率增加尚不清楚。一项随机、前瞻性、对照临床试验在新肾移植患者中静脉使用双膦酸盐帕米膦酸进行。治疗组(PAM)在基线以及第1、2、3和6个月接受帕米膦酸与维生素D和钙治疗。对照组(CON)仅接受维生素D和钙治疗。在第6至12个月期间,对受试者进行观察,不使用帕米膦酸治疗。每月获取骨转换的生化参数,并在基线以及第6和12个月获取骨矿物质密度(BMD)。在接受活体供体移植的受试者亚组中,于基线和6个月时进行矿化骨组织学的骨活检。通过骨密度测定和组织形态计量学测量,PAM在第6和12个月时保留了骨量。CON在第6和12个月时椎体BMD下降(分别为4.8±0.08%和6.1±0.09%)。两组在第6和12个月时骨转换的生化参数相似。骨组织学显示,基线时50%的患者存在低转换骨病。在第6个月时,所有PAM组患者都有动力缺失性骨病,而50%的CON组患者继续存在或出现骨转换降低。帕米膦酸在治疗期间和停药后6个月保留了椎体BMD。帕米膦酸治疗与动力缺失性骨组织学的发生有关。具有动力缺失性骨组织学的改善的BMD在维持肾移植受者的长期骨骼健康方面是否有用,需要进一步研究。