Crawford Bronwyn A L, Kam Cherie, Pavlovic Julie, Byth Karen, Handelsman David J, Angus Peter W, McCaughan Geoffrey W
Royal Prince Alfred Hospital, University of New South Wales, NHMRC Clinical Trials Centre, and University of Sydney, New South Wales, Australia.
Ann Intern Med. 2006 Feb 21;144(4):239-48. doi: 10.7326/0003-4819-144-4-200602210-00005.
Clinically important rapid bone loss occurs within 3 to 6 months after liver transplantation and may be associated with osteoporotic fractures.
To determine whether bisphosphonate treatment with zoledronic acid reduces transplant-related bone loss more than placebo in adults having liver transplantation for chronic liver disease.
12-month randomized, double-blind, placebo-controlled trial.
2 large liver transplantation centers in Australia.
62 adults having liver transplantation for chronic liver disease.
Infusions of zoledronic acid, 4 mg (n = 32), or saline (n = 30) were given within 7 days of transplantation and again at months 1, 3, 6, and 9 after transplantation. All patients received supplementation with calcium carbonate, 600 mg/d, and ergocalciferol, 1000 U/d.
The primary outcome was bone mineral density (BMD) measured by dual x-ray absorptiometry before transplantation and 3, 6, and 12 months later. Secondary outcomes included bone turnover markers that were measured before transplantation and 1, 3, 6, 9, and 12 months later.
There were statistically significant interactions between treatment effects and time for BMD measurements at the lumbar spine (P = 0.002), femoral neck (P = 0.001), and total hip (P < 0.001). Differences in acute bone loss 3 months after transplantation favored zoledronic acid over placebo. Differences between groups in percentage change from baseline adjusted for baseline weight and serum parathyroid hormone (PTH) level were 4.0% (95% CI, 1.1% to 7.0%) for the lumbar spine, 4.7% (CI, 1.9% to 7.6%) for the femoral neck, and 3.8% (CI, 1.7% to 6.0%) for the total hip. At 12 months after transplantation, the difference in percentage change from baseline between the 2 groups adjusted for baseline weight and serum PTH level was 1.1% (CI, -2.1% to 4.4%) for the lumbar spine, 2.7% (CI, 0.0% to 5.4%) for the femoral neck, and 2.4% (CI, 0.1% to 4.7%) for the total hip. Treatment with zoledronic acid induced temporary secondary hyperparathyroidism and postinfusion hypocalcemia statistically significantly more often than did placebo.
The trial was not powered to assess fractures, and 10 of 62 (16%) patients were not included in adjusted analyses because of missing weight or serum PTH measurements.
Treatment with zoledronic acid can prevent bone loss within the first year after liver transplantation.
临床上重要的快速骨质流失发生在肝移植后的3至6个月内，可能与骨质疏松性骨折有关。
确定在因慢性肝病接受肝移植的成年人中，唑来膦酸双膦酸盐治疗是否比安慰剂更能减少与移植相关的骨质流失。
为期12个月的随机、双盲、安慰剂对照试验。
澳大利亚的2个大型肝移植中心。
62名因慢性肝病接受肝移植的成年人。
在移植后7天内输注4毫克唑来膦酸（n = 32）或生理盐水（n = 30），并在移植后的第1、3、6和9个月再次输注。所有患者均补充碳酸钙600毫克/天和麦角钙化醇1000单位/天。
主要结局是通过双能X线吸收法在移植前以及移植后3、6和12个月测量骨密度（BMD）。次要结局包括在移植前以及移植后1、3、6、9和12个月测量的骨转换标志物。
在腰椎（P = 0.002）、股骨颈（P = 0.001）和全髋（P < 0.001）处，治疗效果与BMD测量时间之间存在统计学上的显著交互作用。移植后3个月急性骨质流失的差异有利于唑来膦酸而非安慰剂。根据基线体重和血清甲状旁腺激素（PTH）水平调整后，两组之间从基线变化的百分比差异在腰椎为4.0%（95%CI，1.1%至7.0%），在股骨颈为4.7%（CI，1.9%至7.6%），在全髋为3.8%（CI，1.7%至6.0%）。移植后12个月，根据基线体重和血清PTH水平调整后，两组之间从基线变化的百分比差异在腰椎为1.1%（CI,-2.1%至4.4%），在股骨颈为2.7%（CI，0.0%至5.4%），在全髋为2.4%（CI，0.1%至4.7%）。与安慰剂相比，唑来膦酸治疗更常导致统计学上显著的暂时性继发性甲状旁腺功能亢进和输注后低钙血症。
该试验没有足够的能力评估骨折情况，并且62名患者中有10名（16%）因体重或血清PTH测量值缺失而未纳入调整分析。
唑来膦酸治疗可预防肝移植后第一年的骨质流失。
