Bodingbauer M, Wekerle T, Pakrah B, Roschger P, Peck-Radosavljevic M, Silberhumer G, Grampp S, Rockenschaub S, Berlakovich G, Steininger R, Klaushofer K, Oberbauer R, Mühlbacher F
Division of Transplantation, Department of Surgery, Medical University of Vienna, Vienna, Austria.
Am J Transplant. 2007 Jul;7(7):1763-9. doi: 10.1111/j.1600-6143.2007.01844.x. Epub 2007 May 19.
A randomized controlled prospective open-label single center trial was performed. At the time of transplantation patients were randomly assigned to one of two treatment arms: The study group of 47 patients received zoledronic acid (ZOL, 8 infusions at 4 mg during the first 12 months after LT), calcium (1000 mg/d) and vitamin D (800 IE/d). The control group consisted of 49 patients who received calcium and vitamin D at same doses (CON). The incidence of bone fractures or death was predefined as the primary endpoint. Secondary endpoints included bone mineral density (BMD), serum biochemical markers of bone metabolism, parameters of trabecular bone histomorphometry and mineralization density distribution (BMDD). Patients were followed up for 24 months. Analysis was performed on an intention-to-treat basis. The primary endpoint fracture or death was reached in 26% of patients in the ZOL group and 46% in the CON group (p = 0.047, log rank test). Densitometry results were different between the groups at the femoral neck at 6 months after LT (mean+/-SD BMD ZOL: 0.80 +/- 0.19 g/cm2 vs. CON: 0.73 +/- 0.14 g/cm2, p = 0.036). Mixed linear models of biochemical bone markers showed less increase of osteocalcin in the ZOL group and histomorphometry and BMDD indicated a reduction in bone turnover. Prophylactic treatment with the bisphosphonate zoledronic acid reduces bone turnover and fractures after liver transplantation.
进行了一项随机对照前瞻性开放标签单中心试验。在移植时，患者被随机分配到两个治疗组之一：47例患者的研究组接受唑来膦酸（ZOL，肝移植后前12个月内静脉输注8次，每次4mg）、钙（1000mg/d）和维生素D（800IU/d）。对照组由49例接受相同剂量钙和维生素D的患者组成（CON）。骨折或死亡的发生率被预先定义为主要终点。次要终点包括骨矿物质密度（BMD）、骨代谢的血清生化标志物、小梁骨组织形态计量学参数和矿化密度分布（BMDD）。对患者进行了24个月的随访。分析采用意向性分析。ZOL组26%的患者达到主要终点骨折或死亡，CON组为46%（p=0.047，对数秩检验）。肝移植后6个月时，两组在股骨颈的骨密度测量结果不同（平均±标准差BMD，ZOL组：0.80±0.19g/cm²，CON组：0.73±0.14g/cm²，p=0.036）。骨生化标志物的混合线性模型显示，ZOL组骨钙素的增加较少，组织形态计量学和BMDD表明骨转换降低。双膦酸盐唑来膦酸的预防性治疗可减少肝移植后的骨转换和骨折。
