系统性红斑狼疮患者疾病活动度与骨代谢的相关性研究

The correlation between disease activity and bone metabolism in patients with systemic lupus erythematosus

目的分析不同疾病活动度系统性红斑狼疮(SLE)患者的骨代谢标志物及骨质疏松相关影响因素。方法选取2019年3月至2020年6月在西安交通大学第一附属医院风湿免疫科就诊的417例SLE患者进行回顾性研究,根据SLEDAI评分将其分为非活动组281例、轻度活动组99例及中重度活动组37例。单因素方差分析比较3组之间血清骨代谢标志物[甲状旁腺激素(PTH)、N端骨钙素(NOST)、25羟基维生素总D3(VITDT)、β特殊酸原微生物(β-crossl)、总Ⅰ型前胶原氨基端肽(TP1NP)、血钙、血磷]及骨密度(脊柱L_(1~4)、左股骨)差异,组间两两比较使用Tukey′s法。采用logistic回归法分析骨质疏松的影响因素。结果3组患者在血清VITDT、β-crossl及血钙等骨代谢指标上差异有统计学意义(F=11.66,P<0.001;F=7.22,P<0.001;F=29.38,P<0.001)。与非活动组血清VITDT[(20.3±9.7)ng/ml]、血钙[(2.19±0.15)mmol/L]相比,轻度活动组VITDT[(15.9±9.3)ng/ml]及血钙[(2.09±0.21)mmol/L]明显降低(t=3.94,P<0.001;t=5.10,P<0.001),中重度活动组VITDT[(14.8±7.4)ng/ml]及血钙[(2.00±0.16)mmol/L]也明显降低(t=3.33,P<0.001;t=7.19,P<0.001),且中重度活动组比轻度活动组患者血钙降低更明显(t=2.36,P<0.05)。与非活动组患者血清β-crossl[(419±316)pg/ml]相比,轻度活动组[(543±424)pg/ml]及中重度活动组[(586±343)pg/ml]均明显升高(t=3.06,P<0.001;t=2.99,P<0.001)。与非活动组相比,轻度活动组及中重度活动组脊柱骨密度(BMD)水平(t=2.75,P<0.001;t=2.71,P<0.001)、Z评分(t=5.65,P<0.001;t=4.70,P<0.001)、T评分(t=3.02,P<0.01;t=3.37,P<0.001)均明显降低,而轻度活动组和中重度活动组中重度活动组差异无统计学意义。与非活动组相比,轻度活动组及中重度活动组的左股骨BMD水平(t=2.83,P<0.001;t=2.65,P<0.001)、T评分(t=2.24,P<0.005;t=1.98,P<0.005)均明显降低,而轻度活动组和中重度活动组中重度活动组之间无统计学差别。Logistic回归分析发现:年龄、体质指数(BMI)、SLEDAI评分及激素累计剂量与SLE患者骨质疏松有关联,HR值(95%CI)分别为[1.080(1.052,1.109),P<0.001;0.801(0.704,0.911),P<0.01;1.047(1.025,1.076),P<0.05;1.046(1.006,1.087),P<0.05]。结论SLE患者骨代谢标志物异常及骨密度降低与SLE疾病活动度存在关联,尤其是高龄、低BMI及接受激素累计剂量大的患者,应积极预防骨质疏松的发生。

Objective To analyze the bone turnover markers in systemic lupus erythematosus(SLE)patients with different disease activity and the risk factors of osteoporosis.Methods In this retrospective study,a total of 417 SLE inpatients were enrolled from the Department of Rheumatology and Immunology,the First Affiliated Hospital of Xi′an Jiaotong University,from March 2019 to June 2020.According to SLEDAI score,the patients were divided into 3 groups:281 patients disease with inactive disease group;99 patients with mild active disease group;and 37 patients with moderate/severe active disease.ANOVA test was used to compare the differences in serum bone turnover markers(PTH,NOST,VITDT,β-crossl,TP1NP,Ca and P)and bone density(Spine L_(1~4) and left femur)among the three groups,and Tukey's method was used for the two groups comparison.Logistic regression analysis was used to investigate the risk factors of osteoporosis.Results Serum VITDT,β-crossl and Ca levels were significantly different among the 3 groups(F=11.66,P<0.001;F=7.22,P<0.001;F=29.38,P<0.001).Compared with patients in the inactive group,patients with both the mild disease group(VITDT:t=3.94,P<0.001;Ca:t=5.10,P<0.001)and the moderate/severe disease group(VITDT:t=3.33,P<0.001;Ca:t=7.19,P<0.001)had lower VITDT levels[(20.3±9.7)ng/ml vs.(15.9±9.3)ng/ml vs.(14.8±7.4)ng/ml]and serum Ca levels[(2.19±0.15)mmol/L vs.(2.09±0.21)mmol/L vs.(2.00±0.16)mmol/L].Moreover,the moderate/severe disease group patients had much lower serum Ca levels(t=2.36,P<0.05),compared with patients with the mild disease group.Compared with the patients with inactive group,both the mild activey group(t=3.06,P<0.01)and the moderate/severe activie group(t=2.99,P<0.01)patients had higher serumβ-crossl levels[(419±316)pg/ml vs.(543±424)pg/ml vs.(586±343)pg/ml].Compared with patients with the inactive disease group both patienes with the mild active group and the moderate/severe disease group patients had significantly decreased spine BMD(t=2.75,P<0.01;t=2.71,P<0.01),Z-score(t=5.65,P<0.001;t=4.70,P<0.001),T-score(t=3.02,P<0.01;t=3.37,P<0.001),whereas,no difference was found between the mild disease group and moderate/severe disease group.Compared with the inactive group patients,both the mild active group and moderate/severe disease group patients had lower left femur BMD levels(t=2.83,P<0.001;t=2.65,P<0.001)and T-score(t=2.24,P<0.05;t=1.977,P<0.05)and no difference was found between the mild disease group and the moderate/severe disease group.Logistic regression analysis showed that age[HR(95%CI)=1.080(1.052,1.109),P<0.001],BMI[HR(95%CI)=0.801(0.704,0.911),P<0.001],SLEDAI score[HR(95%CI)=1.047(1.025,1.076),P<0.05]and cumulative glucocorticoids dose[1.046(1.006,1.087),P<0.05]were associated with osteoporosis of SLE patients.Conclusion Abnormal bone metabolism and decreased bone density are associated with SLE disease activity in SLE patients,especially in those with advanced age,low BMI and receiving high cumulative dose of glucocorticoids.Osteoporosis should be proactively prevented in the SLE patients.