NGAL、OPG、RANKL及DAS28对RA骨质疏松的预测作用

Value of neutrophil gelatinase-associated lipocalin，osteoprotegerin，receptor activator of nuclear factor-kappa B ligand，and 28-joint disease activity score in predicting osteoporosis in patients with rheumatoid arthritis

摘要:

目的：通过检测血中中性粒细胞明胶酶相关脂质运载蛋白（neutrophil gelatinase-associated lipocalin，NGAL）、骨护素（osteoprotegerin，OPG）、病情活动度评分 DAS28 与NF-κB配体的受体（receptor activator of NF-κB ligand，RANKL）预测类风湿关节炎（rheumatoid arthritis，RA）骨质疏松意义。方法：选择119例RA患者（RA 组，其中并发骨质疏松症的51例）及68例健康者（对照组），用ELISA法检测RA组与健康对照组的NGAL、骨形成指标OPG及骨吸收指标RANKL，详细记录骨矿物质含量（bone mineral density，BMD）、病情活动性评分（disease activity score 28，DAS28）与临床、实验室资料。结果：①RA病人血清NGAL、RANKL水平较健康对照组明显增高（均P=0.000），血清OPG、OPG/RANKL、BMD水平较对照组明显降低（均P=0.000），差异有统计学意义。②RA合并有骨质疏松症的病人血清NGAL[（152.12±28.34）ng/mL]、RANKL水平[（112.23±18.45） pmol/L]及DAS28（4.21±0.56）评分较无骨质疏松症组明显增高[NGAL（124.50±18.52） ng/mL，P=0.000；RANKL （103.89±14.14） pmol/L，P=0.008；DAS28 3.52±0.70，P=0.000]；血清OPG[（114.35±17.00） ng/L]、OPG/RANKL（1.06±0.24）、BMD（-3.73±0.69）水平较无骨质疏松症组明显降低[OGP（120.56±15.35） ng/L，P=0.039；OPG/RANKL 1.18±0.24，P=0.006；BMD -0.57±0.76，P=0.000]，差异有统计学意义。③Spearman相关分析显示，NGAL、DAS28与BMD严重程度呈正相关，rs分别为0.532、0.437，P值分别为0.000、0.000，其相关性对RA合并有骨质疏松症有早期诊断的实际意义。④采用ROC曲下线面积分析，当DAS28的最佳诊断参考值为4.11时（诊断敏感性和特异性分别为68.6%、77.9%）、NGAL最佳诊断参考值为148.80 ng/mL时（诊断敏感性和特异性分别为60.8%、89.7%）、RANKL为100.77 pmol/L时（诊断敏感性和特异性分别为64.7%、54.4%），可考虑RA患者合并有骨质疏松症的可能。结论：血清NGAL、RANKL作为炎症指标，其水平及DAS28活动性评分大于等于相应的最佳诊断值可以考虑RA病人合并有了骨质疏松症的可能，对调整治疗方案、极早干预骨质疏松症的发生与发展有一定的临床价值。

Abstract:

Objective：To investigate the value of blood neutrophil gelatinase-associated lipocalin（NGAL），osteoprotegerin（OPG），28-joint disease activity score（DAS28），and receptor activator of nuclear factor-kappa B ligand（RANKL） in predicting osteoporosis in patients with rheumatoid arthritis（RA）. Methods：A total of 119 RA patients were enrolled as RA group，among whom 51 had osteo－porosis in addition to RA，and 68 healthy individuals were enrolled as control group. ELISA was used to measure NGAL，OPG（an index for bone formation），and RANKL（an index for bone resorption） for both groups，and bone mineral density（BMD），DAS28，and clinical and laboratory data were recorded in detail. Results：Compared with the control group，the RA group had significantly higher serum levels of NGAL and RANKL（both P=0.000） and significantly lower serum OPG level，OPG/RANKL ratio，and BMD（all P=0.000）. Compared with those without osteoporosis，the RA patients with osteoporosis had sig－nificantly higher serum NGAL（152.12±28.34 ng/mL vs. 124.50±18.52 ng/mL，P=0.000），serum RANKL level（112.23±18.45 pmol/L vs. 103.89±14.14 pmol/L，P=0.008），and DAS28 score（4.21±0.56 vs. 3.52±0.70，P=0.000），as well as significantly lower serum OPG（114.35±17.00 ng/L vs. 120.56±15.35 ng/L，P=0.039），OPG/RANKL ratio（1.06±0.24 vs. 1.18±0.24，P=0.006），and BMD（-3.73±0.69 vs. -0.57±0.76，P=0.000）. Spearman correlation analysis showed that NGAL and DAS28 were positively correlated with the severity of BMD（rs=0.532 and 0.437，P=0.000 and 0.000），and such correlation had a certain value in the early diagnosis of osteoporosis in RA patients. The area under the receiver operating characteristic curve showed that DAS28 with a cut-off value of 4.11（a sensitivity of 68.6% and a specificity of 77.9%），NGAL with a cut-off value of 148.80 ng/mL（a sensitivity of 60.8% and a specificity of 89.7%），and RANKL with a cut-off value of 100.77 pmol/L（a sensitivity of 64.7% and a specificity of 54.4%） helped with the diagnosis of osteoporosis in RA patients. Conclusion：Serum levels of the inflammatory markers NGAL and RANKL and DAS28 score at their respective cut-off values can help with the diagnosis of osteoporosis in RA patients. They also have a certain clinical value in adjustment of treatment regimens and early intervention of osteoporosis.