血清成纤维生长因子23水平在类风湿关节炎及其骨质疏松中的临床研究

Clinical study of serum fibroblast growth factor 23 levels in patients with rheumatoid arthritis and their association with osteoporosis

目的检测并分析血清成纤维生长因子23（FGF23）水平与RA患者病情及其骨质疏松（OP）发生的关系。方法采用ELISA法测定174例RA患者和88名健康人血清FGF23浓度，采用双能X线吸收法测定骨密度（BMD），详细记录RA患者各临床及实验室指标，计算RA疾病活动性积分（DAS28）和日常生活能力（HAQ），进行双手X线片并计算Sharp评分。统计学方法采用t检验、非参数检验、χ2检验、相关分析和多元Logiatic回归分析。结果RA患者血清FGF23水平明显高于正常对照组[145.46（67.67，245.93）pg/ml，32.64（12.34，44.70）pg/ml，Z=11.416，P〈0.01]；RA患者中血清FGF23阳性率（≥71.95 pg/ml）为74.7%，高于正常对照组（4.5%）（χ2=115.16，P〈0.01）。血清FGF23≥48.56 pg/ml时对RA具有较高的诊断价值意义，敏感度为89.1%，特异度为85.2%（AUC=0.932，约登指数=0.743，P〈0.01）。在血清FGF23≥48.56 pg/ml的RA患者中，FGF23阳性的RA患者中患者疼痛评分、关节肿胀数和HAQ均高于FGF23阴性组（P〈0.05）；股骨颈、Ward区三角、大转子、总髋部、L4及L1~4的骨密度均低于FGF23阴性的RA患者（P〈0.05）；抗CCP抗体与FGF23浓度呈负相关（r=-0.171，P=0.035），DAS28与FGF23阳性呈正相关（rs=0.163，P=0.045）；股骨颈、Ward区三角、大转子、总髋部、L4及L1~4的骨密度与FGF23阳性呈负相关（P〈0.05）。多元Logistic回归分析发现，女性[OR=8.518，95%CI（2.636，27.522），P〈0.01]，高龄[OR=1.129，95%CI（1.079，1.180），P〈0.01]，Sharp评分[OR=1.008，95%CI（1.003，1.013），P=0.01]均为RA患者发生OP的危险因素；BMI[OR=0.801，95%CI（0.707，0.909），P=0.001]为RA患者发生OP的保护因素。结论RA患者血清中FGF23水平明显升高，且与RA的疾病活动性及骨密度存在一定相关性。

Objective To explore the serum levels of fibroblast growth factor 23 （FGF23） in patients with rheumatoid arthritis （RA） and to investigate the relationship between FGF23 and RA disease activity and the occurrence of osteoporosis （OP）.Methods Serum levels of FGF23 from 174 cases of patients with RA and 88 normal subjects were detected by enzyme linked immunosorbent assay （ELISA）. Bone mineral density （BMD） was measured by dual energy X-ray absorptiometry. All the clinical and laboratory indexes of RA patients were recorded in details, disease activity score （DAS28） and health assess questionnaire （HAQ） were also calculated in the meantime. Radiographic changes in both hands of RA patients were assessed by Sharp＇s method. T test, nonparametric test, χ2 test, correlation analysis and Logistic regressive analysis were used for statistical analysis. Results Serum levels of FGF3 [145.46（67.67, 245.93） pg/ml] in RA patients were higher than the control group [32.64（12.34, 44.70） pg/ml, Z=11.416, P〈0.01]. The positive rate of serum levels of FGF23 （≥71.95 pg/ml） in RA was 74.7%（130/174）, while the positive rate in control was 4.5%（4/88,χ2=115.16, P〈0.01）. The threshold of FGF23 serum levels for diagnosing RA was 48.56 pg/ml （AUC=0.932, Youden index=0.743, P〈0.01, sensitivity 89.1%, specificity 85.2%）. In RA patients with serum FGF23≥48.56 pg/ml, compared with negative FGF23 group, VAS, HAQ, number of joint swelling and BMD at femoral neck,Ward, GT, Total hip, L4 and L1-4 were significantly higher in FGF23 positive group （P〈0.05）. Linear correlation analysis found that in RA patients with serum FGF23≥48.56 pg/ml, anti-CCP was negatively correlated with serum FGF23 levels （r=-0.171, P=0.035）. And DAS28 was positively correlated with serum FGF23 （r=0.163, P=0.045）. BMD at femoral neck, Ward, GT, Total hip, L4 and L1-4 were negatively correlated with serum FGF23 （P〈0.05）. Results of logistic regression analysis showed that sex （OR=8.518, 95%CI （2.636, 27.522）, P〈0.01, age [OR=1.129, 95%CI （1.079, 1.180）, P〈0.01] and Sharp score [OR=1.008, 95%CI（1.003, 1.013）, P=0.001] were risk factors for OP in RA patients. BMI[OR=0.801, 95%CI（0.707, 0.909）, P=0.001] was a protective factor for OP in RA patients.