Bonani M, Frey D, Brockmann J, Fehr T, Mueller T F, Saleh L, von Eckardstein A, Graf N, Wüthrich R P
Division of Nephrology, University Hospital Zürich and University of Zürich, Zürich, Switzerland.
Division of Rheumatology, University Hospital Zürich and University of Zürich, Zürich, Switzerland.
Am J Transplant. 2016 Jun;16(6):1882-91. doi: 10.1111/ajt.13692. Epub 2016 Feb 29.
We conducted an open-label, prospective, randomized trial to assess the efficacy and safety of RANKL inhibition with denosumab to prevent the loss of bone mineral density (BMD) in the first year after kidney transplantation. Ninety kidney transplant recipients were randomized 1:1 2 weeks after surgery to receive denosumab (60 mg at baseline and 6 months) or no treatment. After 12 months, total lumbar spine areal BMD (aBMD) increased by 4.6% (95% confidence interval [CI] 3.3-5.9%) in 46 patients in the denosumab group and decreased by -0.5% (95% CI -1.8% to 0.9%) in 44 patients in the control group (between-group difference 5.1% [95% CI 3.1-7.0%], p < 0.0001). Denosumab also increased aBMD at the total hip by 1.9% (95% CI, 0.1-3.7%; p = 0.035) over that in the control group at 12 months. High-resolution peripheral quantitative computed tomography in a subgroup of 24 patients showed that denosumab increased volumetric BMD at the distal tibia and radius (all p < 0.05). Biomarkers of bone turnover (C-terminal telopeptide of type I collagen, procollagen type I N-terminal propeptide) markedly decreased with denosumab (all p < 0.0001). Episodes of cystitis and asymptomatic hypocalcemia occurred more often with denosumab, whereas graft function, rate of rejections, and incidence of opportunistic infections were similar. In conclusion, denosumab increased BMD in the first year after kidney transplantation but was associated with more frequent episodes of urinary tract infection.
我们进行了一项开放标签、前瞻性、随机试验，以评估地诺单抗抑制核因子κB受体活化因子配体（RANKL）预防肾移植后第一年骨矿物质密度（BMD）丢失的疗效和安全性。90例肾移植受者在术后2周按1:1随机分组，分别接受地诺单抗（基线和6个月时各60mg）或不接受治疗。12个月后，地诺单抗组46例患者的腰椎总骨面积密度（aBMD）增加了4.6%（95%置信区间[CI]3.3 - 5.9%），而对照组44例患者的腰椎总骨面积密度下降了 -0.5%（95%CI -1.8%至0.9%）（组间差异5.1%[95%CI 3.1 - 7.0%]，p < 0.0001）。在12个月时，地诺单抗组全髋关节的aBMD也比对照组增加了1.9%（95%CI，0.1 - 3.7%；p = 0.035）。对24例患者亚组进行的高分辨率外周定量计算机断层扫描显示，地诺单抗增加了胫骨远端和桡骨的体积骨密度（所有p < 0.05）。骨转换生物标志物（I型胶原C末端肽、I型前胶原N末端前肽）用地诺单抗治疗后显著下降（所有p < 0.0001）。地诺单抗组膀胱炎和无症状性低钙血症的发作更为频繁，而移植肾功能、排斥反应发生率和机会性感染发生率相似。总之，地诺单抗增加了肾移植后第一年的骨密度，但与更频繁的尿路感染发作有关。
