Bonani Marco, Meyer Ursina, Frey Diana, Graf Nicole, Bischoff-Ferrari Heike A, Wüthrich Rudolf P
Division of Nephrology, University Hospital Zürich and University Zürich, Zürich, Switzerland.
Kidney Blood Press Res. 2016;41(5):614-622. doi: 10.1159/000447930. Epub 2016 Sep 14.
BACKGROUND/AIMS: In a randomized controlled clinical trial in kidney transplant recipients (NCT01377467) we have recently shown that RANKL inhibition with denosumab significantly improved areal bone mineral density (aBMD) when given during the first year after transplantation. The effect of denosumab on skeletal microstructure and bone strength in kidney transplant recipients is not known.
The purpose of the present bone microarchitecture ancillary study was to investigate high-resolution peripheral quantitative computed tomography (HRpQCT) data from the distal tibia and distal radius in 24 study patients that had been randomized to receive either two injections of denosumab 60 mg at baseline and after 6 months (n=10) or no treatment (n=14).
Consistent with the full trial findings, denosumab reduced biomarkers of bone turnover, and significantly increased aBMD at the lumbar spine (median difference of 4.7%; 95% confidence interval [CI] 2.6 - 7.8; p<0.001). Bone quality as assessed by total and cortical volumetric bone mineral density (Tot. vBMD, Ct.vBMD) and cortical thickness (Ct.Th) increased significantly at the tibia, while changes at the radius were less pronounced. The trabecular volumetric BMD (Tb.vBMD), thickness (Tb. Th), separation (Tb.Sp) and number (Tb.N) and the cortical porosity (Ct.Po) at the tibia and the radius did not significantly change in both treatment groups. Micro-finite element analysis (µFEA) showed that bone stiffness increased significantly at the tibia (median difference 5.6%; 95% CI 1.8% - 9.2%; p=0.002) but not at the radius (median difference 2.9%, 95% CI -3.7% - 9.1%; p=0.369). Likewise, failure load increased significantly at the tibia (median difference 5.1%; 95% CI 2.1% - 8.1%; p=0.002) but not at the radius (median difference 2.4%, 95% CI -3.2% - 8.5%; p=0.336).
These findings demonstrate that denosumab improves bone density and bone quality in first-year kidney transplant recipients at risk to develop osteoporosis.
背景/目的：在一项针对肾移植受者的随机对照临床试验（NCT01377467）中，我们最近发现，在移植后的第一年使用地诺单抗抑制核因子κB受体活化因子配体（RANKL）可显著提高骨面积骨密度（aBMD）。地诺单抗对肾移植受者骨骼微结构和骨强度的影响尚不清楚。
本骨微结构辅助研究的目的是调查24例研究患者胫骨远端和桡骨远端的高分辨率外周定量计算机断层扫描（HRpQCT）数据，这些患者被随机分为两组，一组在基线和6个月后接受两次60mg地诺单抗注射（n = 10），另一组不接受治疗（n = 14）。
与整个试验结果一致，地诺单抗降低了骨转换生物标志物，并显著提高了腰椎的aBMD（中位数差异为4.7%；95%置信区间[CI] 2.6 - 7.8；p<0.001）。通过总骨体积骨密度和皮质骨体积骨密度（Tot. vBMD、Ct.vBMD）以及皮质厚度（Ct.Th）评估的骨质量在胫骨处显著增加，而在桡骨处的变化则不太明显。两个治疗组中，胫骨和桡骨的小梁体积骨密度（Tb.vBMD）、厚度（Tb. Th）、间距（Tb.Sp）和数量（Tb.N）以及皮质孔隙率（Ct.Po）均无显著变化。微有限元分析（µFEA）显示，胫骨的骨刚度显著增加（中位数差异5.6%；95% CI 1.8% - 9.2%；p = 0.002），而桡骨未增加（中位数差异2.9%，95% CI -3.7% - 9.1%；p = 0.369）。同样，胫骨的破坏载荷显著增加（中位数差异5.1%；95% CI 2.1% - 8.1%；p = 0.002），而桡骨未增加（中位数差异2.4%，95% CI -3.2% - 8.5%；p = 0.336）。
这些发现表明，地诺单抗可改善有骨质疏松风险的第一年肾移植受者的骨密度和骨质量。
