Shiota Jun, Izumi Naoki, Kasahara Hitoshi, Tagawa Hitoshi, Chiba Tetsuo, Nihei Hiroshi
Department of Internal Medicine, Kichijoji Asahi Hospital, Tokyo, Japan.
Nihon Jinzo Gakkai Shi. 2010;52(8):1022-8.
Osteoprotegerin (OPG) inhibits interaction of the receptor-activator of nuclear factor-kappaB (RANK) ligand (RANKL) with its receptor RANK, which is expressed on osteoclasts. OPG appeared to accelerate vascular calcification in vitro by the inhibition of vascular osteoclast-like cells. On the contrary, early-onset arterial calcification was observed in OPG-deficient mice. We measured the coronary artery calcification score (CACS) and abdominal aortic calcification score (AAoCS) by multi-detector computed tomography in 30 pre-dialysis CKD patients (eGFR 20 mL/min on average). Biomarkers were measured, including serum OPG, soluble RANKL (sRANKL) and tartrate-resistant acid phosphatase (TRACP) -5b (the biomarker of osteoclasts independent of renal function). The median values of CACS and AAoCS were 54.4 and 1,088 Agatston units (AU), respectively. Serum OPG was increased and serum sRANKL was decreased. In a multivariate logistic regression analysis using CACS > or = 100 AU as the outcome variable, CACS was found to be positively correlated with serum corrected Ca x iP product and serum OPG, though it was not correlated with serum TRACP-5b. ROC curve analysis showed that the serum OPG cutoff value predicting CACS > or = 100 AU was 5.2 pmol/L (624 pg/mL). In a stepwise regression analysis, log (AAoCS + 1) was positively correlated with serum OPG alone, but it was not correlated with age, eGFR, serum albumin and bone alkaline phosphatase (BAP). No correlation was found between serum OPG and serum TRACP-5b. In conclusion, vascular calcification in pre-dialysis CKD patients was correlated with an increase in OPG, but was independent of serum TRACP-5b. The decrease in serum sRANKL may have been caused by the increase in OPG production.
骨保护素（OPG）可抑制核因子-κB受体激活剂（RANK）配体（RANKL）与其在破骨细胞上表达的受体RANK之间的相互作用。OPG在体外似乎通过抑制血管破骨细胞样细胞而加速血管钙化。相反，在OPG缺陷小鼠中观察到早发性动脉钙化。我们通过多排螺旋计算机断层扫描测量了30例透析前慢性肾脏病患者（平均估算肾小球滤过率[eGFR]为20 mL/min）的冠状动脉钙化评分（CACS）和腹主动脉钙化评分（AAoCS）。检测了生物标志物，包括血清OPG、可溶性RANKL（sRANKL）和抗酒石酸酸性磷酸酶（TRACP）-5b（独立于肾功能的破骨细胞生物标志物）。CACS和AAoCS的中位数分别为54.4和1088阿加斯顿单位（AU）。血清OPG升高而血清sRANKL降低。在以CACS≥100 AU作为结果变量的多因素逻辑回归分析中，发现CACS与血清校正钙×磷乘积及血清OPG呈正相关，尽管它与血清TRACP-5b无关。ROC曲线分析显示，预测CACS≥100 AU的血清OPG临界值为5.2 pmol/L（624 pg/mL）。在逐步回归分析中，log（AAoCS + 1）仅与血清OPG呈正相关，但与年龄、eGFR、血清白蛋白和骨碱性磷酸酶（BAP）无关。血清OPG与血清TRACP-5b之间未发现相关性。总之，透析前慢性肾脏病患者的血管钙化与OPG升高相关，但与血清TRACP-5b无关。血清sRANKL降低可能是由OPG产生增加所致。
