系统性红斑狼疮合并骨坏死的影响因素分析

雷佳敏; 侯睿宏; 米良煜; 张莉芸; 高晋芳; 许珂

doi:10.16766/j.cnki.issn.1674-4152.003495

系统性红斑狼疮合并骨坏死的影响因素分析

doi: 10.16766/j.cnki.issn.1674-4152.003495

雷佳敏^{1, 2},
侯睿宏²,
米良煜²,
张莉芸²,
高晋芳²,
许珂^2, ,

1.
山西医科大学公共卫生学院卫生统计学教研室，山西太原 030001
2.
山西白求恩医院风湿免疫科，山西太原 030032

基金项目:

国家自然科学基金项目 82271761

详细信息

通讯作者:
许珂，E-mail：zhaoxuke@hotmail.com

中图分类号: R593.241 R681
计量
- 文章访问数: 127
- HTML全文浏览量: 90
- PDF下载量: 4
- 被引次数: 0
出版历程
- 收稿日期: 2023-07-18
- 网络出版日期: 2024-07-20

Influencing factors analysis of systemic lupus erythematosus with osteonecrosis

1.
Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, China

摘要

摘要: 目的分析系统性红斑狼疮合并骨坏死的相关影响因素, 以减少对患者生活质量的影响。方法选取2013年1月-2022年12月山西白求恩医院风湿免疫科住院的系统性红斑狼疮(SLE)合并骨坏死(ON)者65例为骨坏死组, 按年龄、性别1:1随机匹配65例未合并ON者为非骨坏死组。比较2组临床症状、实验室检查及治疗情况, 采用logistic回归分析研究SLE合并ON的危险因素。结果骨坏死组中双侧ON 53例(81.5%); 骨表现为疼痛29例(44.6%), 复合多症状18例(27.6%)。单因素分析显示, 2组SLE病程、激素累积时间、停经史、神经系统受累、肌痛肌无力差异均有统计学意义, 实验室指标中白细胞计数、总T细胞及Ts细胞百分比、NKT细胞百分比及绝对值、标准化dRVVT比值、活化部分凝血活酶时间, 用药情况中阿司匹林、他汀类、二磷酸盐、羟氯喹史和免疫抑制剂史差异均有统计学意义(P < 0.05)。多因素logistic回归分析显示, 总T细胞百分比、标准化dRVVT比值是SLE合并ON的影响因素。结论 SLE治疗时应合理使用免疫抑制剂, 注意平衡药物间相互作用, 同时需特别关注神经系统受累及肌痛肌无力患者。淋巴细胞亚群中的Ts细胞在ON中起到重要的调节作用。标准化dRVVT比值高者发生ON的风险更高, 或可预测ON的发生, 在临床诊断和治疗中应提高警惕。
- 系统性红斑狼疮 /
- 骨坏死 /
- 影响因素
Abstract: Objective To analyze the factors associated with osteonecrosis (ON) in patients with systemic lupus erythematosus (SLE) in order to reduce the impact on patients'quality of life. Methods A total of 65 SLE patients with ON (ON group) and 65 SLE patients without ON (non-ON group) who hospitalized in the Department of Rheumatology and Immunology of Shanxi Bethune Hospital from January 2013 to December 2022 were selected.The clinical symptoms, laboratory examination and treatment were compared between the two groups.Logistic regression was used to analyze the risk factors for SLE complicated with ON. Results Among the case groups, 53 cases (81.5%) were bilateral ON; There were 29 cases (44.6%) of bone pain and 18 cases (27.6%) of complex multiple symptoms.In univariate analysis, there were statistically significant differences in disease course, hormone accumulation time, menopausal history, nervous system involvement and myalgia muscle weakness, and there were statistically significant differences in white blood cell count, percentage of total T cells and suppressor T (Ts) cells, percentage and absolute value of natural killer T (NKT) cells, standardized dilute Russell's viper venom time (dRVVT) ratio, activated partial thromboplastin time, and history of aspirin, statins, bisphosphonates, hydroxychloroquine and immunosuppressants in medication use (P < 0.05).Multivariate logistic regression analysis showed that the percentage of total T cells and the ratio of standardized dRVVT were the influencing factors of SLE with ON. Conclusion Appropriate use of immunosuppressants, attention to balancing medication interactions in SLE treatment, and special attention to patients with nervous system involvement and muscle pain and weakness.Ts cells in the lymphocyte subpopulation play an important regulatory role in ON.Individuals with higher standardized dRVVT ratios are more likely to have ON or may predict the occurrence of ON.Therefore, caution should be used in clinical diagnosis and treatment.
- Systemic lupus erythematosus /
- Osteonecrosis /
- Influencing factors

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表 1 2组SLE患者一般资料与实验室指标比较

Table 1. Comparison of general data and laboratory indicators for two groups of SLE patients

项目	ON组(n=65)	非ON组(n=65)	统计量	P值
性别(女性/男性, 例)	55/10	60/5	-1.367^a	0.172
BMI(x±s)	23.5±4.6	22.7±4.0	0.976^b	0.331
年龄(x±s, 岁)	36.0±1.6	36.4±2.1	0.375^b	0.708
确诊SLE年龄[M(P₂₅, P₇₅), 岁]	25.5(21.0, 32.8)	31.5(20.8, 47.3)	-0.890^c	0.374
SLE病程[M(P₂₅, P₇₅), 月]	62.0(33.0, 108.8)	23.0(0.0, 102.0)	-3.455^c	0.001
激素累积时间[M(P₂₅, P₇₅), 月]	55.0(28.5, 98.3)	14.0(0.0, 74.0)	-3.419^c	0.001
WBC(x±s, ×10⁹/L)	6.85±0.48	5.48±0.44	2.572^b	0.010
RBC(x±s, ×10⁹/L)	3.76±0.87	3.66±0.85	0.664^b	0.508
PLT(x±s, ×10⁹/L)	183.48±90.95	155.52±86.64	1.789^b	0.076
HGB(x±s, g/L)	110.36±24.24	111.39±24.54	0.239^b	0.812
C3(x±s，g/L)	0.76±0.30	0.63±0.26	-2.301^b	0.023
C4(x±s，g/L)	0.14±0.09	0.12±0.07	1.222^b	0.224
TC(x±s, mmol/L)	3.55±1.78	3.39±1.23	0.429^b	0.669
TG(x±s, mmol/L)	3.09±2.46	2.56±1.44	1.354^b	0.179
HDL(x±s, mmol/L)	1.16±0.39	1.13±0.43	0.288^b	0.774
LDL(x±s, mmol/L)	2.74±1.16	2.44±0.78	1.459^b	0.148
总T细胞[M(P₂₅, P₇₅), %]	80.1(75.3, 87.6)	76.2(66.4, 82.8)	2.175^c	0.030
总T细胞[M(P₂₅, P₇₅), 个/μL]	752.5(436.5, 1 189.8)	609.5(377, 3, 991.5)	1.346^c	0.178
Th细胞(x±s, %)	32.90±11.14	31.24±12.31	0.679^b	0.499
Th细胞[M(P₂₅, P₇₅), 个/μL]	262.5(125.0, 5.0)	285.0(150.5, 428.0)	0.314^c	0.754
Ts细胞(x±s, %)	44.16±14.43	38.71±11.46	2.005^b	0.048
Ts细胞[M(P₂₅, P₇₅), 个/μL]	424.0(255.0, 591.0)	292.5(187.0, 431.0)	1.560^c	0.119
NKT细胞[M(P₂₅, P₇₅), %]	1.6(0.8, 2.8)	3.3(1.4, 6.2)	-2.351^c	0.019
NKT细胞[M(P₂₅, P₇₅), 个/μL]	15.5(6.5, 35.5)	32.5(9.3, 69.5)	-2.100^c	0.036
Th/Ts[M(P₂₅, P₇₅)]	0.8(0.5, 1.1)	0.8(0.6, 1.1)	0.305^c	0.761
标准化dRVVT比值[例(%)]	29(44.6)	15(23.1)	11.773^a	0.001
APTT[例(%)]	17(26.2)	26(40.0)	4.073^a	0.044
抗dsDNA抗体[例(%)]	22(33.8)	26(40.0)	0.544^a	0.461
ANA[例(%)]	23(35.4)	31(47.7)	2.819^a	0.053
注：^a为χ²值，^b为t值，^c为Z值。标准化dRVVT比值分组标准, 正常值0.8~1.2为阴性(0)，其余为阳性(1)；APTT分组标准, 正常值23~37 s为阴性(0)，其余为阳性(1)。

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表 2 2组SLE患者个人史、临床特征及治疗情况比较[例(%)]

Table 2. Comparison of personal history, clinical features, and treatment in two groups of SLE patients [cases(%)]

项目	ON组 (n=65)	非ON组 (n=65)	χ²值	P值
临床特征
肾脏受累	39(60.0)	41(63.1)	0.130	0.718
血液系统受累	51(78.5)	47(72.3)	0.663	0.415
神经系统受累	22(33.8)	12(18.5)	3.983	0.046
红斑	34(52.3)	24(36.9)	3.780	0.052
关节痛	46(70.8)	38(58.5)	2.152	0.142
肌痛肌无力	10(15.4)	3(4.6)	4.188	0.041
雷诺现象	11(16.9)	13(20.0)	0.204	0.651
治疗情况
糖皮质激素	64(98.5)	58(89.2)	4.795	0.238
激素冲击治疗	14(21.5)	7(10.8)	2.783	0.702
羟氯喹史	48(73.8)	29(44.6)	11.500	0.001
免疫抑制剂史	59(90.8)	41(63.1)	14.040	< 0.001
阿司匹林	32(49.2)	11(16.9)	15.320	< 0.001
抗凝类	58(89.2)	55(84.6)	0.609	0.435
他汀类	24(36.9)	5(7.7)	16.020	< 0.001
钙	58(89.2)	54(83.1)	1.032	0.310
二磷酸盐	47(72.3)	10(15.4)	42.770	< 0.001
个人史
输血史	11(16.9)	6(9.2)	1.692	0.193
停经史	21(32.3)	5(7.7)	12.024	0.001

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表 3 SLE患者合并ON的多因素logistic回归分析

Table 3. Multifactorial logistic regression analysis of ON in SLE patients

变量	B	SE	Waldχ²	P值	OR(95% CI)
总T细胞	0.141	0.058	5.806	0.016	1.151(1.027~1.291)
Ts细胞	-0.094	0.066	1.995	0.158	0.910(0.799~1.037)
NKT细胞	-0.774	0.390	3.936	0.047	0.461(0.215~0.991)
NKT细胞	0.025	0.018	1.886	0.170	1.025(0.990~1.062)
标准化dRVVT比值	1.997	1.141	3.063	0.080	7.363(0.787~68.891)
APTT	0.108	0.109	0.986	0.321	1.114(0.900~1.379)
WBC	0.175	0.201	0.755	0.385	1.191(0.803~1.766)
停经史	3.498	1.758	3.957	0.047	33.041(1.053~1 036.772)
SLE病程	-0.001	0.007	0.031	0.860	0.999(0.985~1.013)
肌痛肌无力	5.352	2.710	3.900	0.048	211.084(1.041~42 795.42)
神经系统受累	-0.069	1.089	0.004	0.949	0.933(0.110~7.894)

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参考文献(26)

[1]	张嵩, 谢长好, 陈琳洁. 女性系统性红斑狼疮合并膝关节骨梗死的临床分析[J]. 中华全科医学, 2020, 18(7): 1103-1106. doi: 10.16766/j.cnki.issn.1674-4152.001439 HANG S, XIE C H, CHEN L J. Clinical analysis of bone infarction of knee joint with female systemic lupus erythematosus[J]. Chinese Journal of General Practice, 2020, 18(7): 1103-1106. doi: 10.16766/j.cnki.issn.1674-4152.001439
[2]	KANEKO K, CHEN H, KAUFMAN M, et al. Glucocorticoid-induced osteonecrosis in systemic lupus erythematosus patients[J]. Clin Transl Med, 2021, 11(10): e526. DOI: 10.1002/ctm2.526.
[3]	李宁宁, 陈奕均, 冷晓梅, 等. 系统性红斑狼疮并发骨坏死118例临床特点及危险因素分析[J]. 中华内科杂志, 2021, 60(8): 744-750. doi: 10.3760/cma.j.cn112138-20200916-00818 LI N N, CHEN Y J, LENG X M. Analysis of clinical characteristics and risk factors of 118 cases of systemic lupus erythematosus complicated with osteonecrosis[J]. Chinese Journal of Internal Medicine, 2021, 60(8): 744-750. doi: 10.3760/cma.j.cn112138-20200916-00818
[4]	KALLAS R, LI J, PETRI M. Predictors of osteonecrosis in systemic lupus erythematosus: a prospective cohort study[J]. Arthritis Care Res(Hoboken), 2022, 74(7): 1122-1132. doi: 10.1002/acr.24541
[5]	HISADA R, KATO M, OHNISHI N, et al. Antiphospholipid score is a novel risk factor for idiopathic osteonecrosis of the femoral head in patients with systemic lupus erythematosus[J]. Rheumatology(Oxford), 2019, 58(4): 645-649. doi: 10.1093/rheumatology/key365
[6]	WEI Q, ZHOU M, LIU J, et al. Relationship between osteonecrosis and antiphospholipid antibodies in patients with systemic lupus erythematosus: a systematic review protocol[J]. BMJ Open, 2021, 11(7): e46163. DOI: 10.1136/bmjopen-2020-046163.
[7]	ARINGER M, COSTENBADER K, DAIKH D, et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus[J]. Ann Rheum Dis, 2019, 78(9): 1151-1159. DOI: 10.1136/annrheumdis-2018-214819.
[8]	GLADMAN D D, IBANEZ D, UROWITZ M B. Systemic lupus erythematosus disease activity index 2000[J]. J Rheumatol, 2002, 29(2): 288-291.
[9]	SUN S, WANG Q, GONG Y, et al. Multifocal osteonecrosis affecting all four limbs in systemic lupus erythematosus: a case report[J]. Exp Ther Med, 2019, 18(4): 2475-2478.
[10]	LESPASIO M J, SODHI N, MONT M A. Osteonecrosis of the hip: a primer[J]. Perm J, 2019, 23: 18-100.
[11]	ZHENG Y, ZHENG Z, ZHANG K, et al. Osteonecrosis in systemic lupus erythematosus: systematic insight from the epidemiology, pathogenesis, diagnosis and management[J]. Autoimmun Rev, 2022, 21(2): 102992. DOI: 10.1016/j.autrev.2021.102992.
[12]	LONG Y, ZHANG S, ZHAO J, et al. Risk of osteonecrosis in systemic lupus erythematosus: an 11-year Chinese single-center cohort study[J]. Lupus, 2021, 30(9): 1459-1468. doi: 10.1177/09612033211021166
[13]	曲立阳, 李建军. 选择性免疫抑制剂对骨代谢影响的研究进展[J]. 中国医药科学, 2022, 12(11): 57-60. doi: 10.3969/j.issn.2095-0616.2022.11.015 QYU L Y, LI J J. Research progress on the impacts of selective immunosuppressants on bone metabolism[J]. China Medicine and Pharmacy, 2022, 12(11): 57-60. doi: 10.3969/j.issn.2095-0616.2022.11.015
[14]	JIN W, YANG X, LU M. Juvenile-onset multifocal osteonecrosis in systemic lupus erythematosus: a case report[J]. Medicine(Baltimore), 2021, 100(2): e24031. DOI: 10.1097/MD.0000000000024031.
[15]	ATTARDO S, MUSUMECI O, VELARDO D, et al. Statins neuromuscular adverse effects[J]. Int J Mol Sci, 2022, 23(15): 8364. DOI: 10.3390/ijms23158364.
[16]	CRISAN E, PATIL V K. Neuromuscular complications of statin therapy[J]. Curr Neurol Neurosci Rep, 2020, 20(10): 47. DOI: 10.1007/s11910-020-01064-0.
[17]	CAMERINO G M, TARANTINO N, CANFORA I, et al. Statin-induced myopathy: translational studies from preclinical to clinical evidence[J]. Int J Mol Sci, 2021, 22(4): 2070. DOI: 10.3390/ijms22042070.
[18]	INDIRLI R, LANZI V, MANTOVANI G, et al. Bone health in functional hypothalamic amenorrhea: what the endocrinologist needs to know[J]. Front Endocrinol(Lausanne), 2022, 13: 946695. DOI: 10.3389/fendo.2022.946695.
[19]	HERRADA A A, ESCOBEDO N, IRURETAGOYENA M, et al. Innate immune cells'contribution to systemic lupus erythematosus[J]. Front Immunol, 2019, 10: 772. DOI: 10.3389/fimmu.2019.00772.
[20]	MA J, GE J, GAO F, et al. The role of immune regulatory cells in nontraumatic osteonecrosis of the femoral head: a retrospective clinical study[J]. Biomed Res Int, 2019, 2019: 1302015. DOI: 10.1155/2019/1302015.
[21]	侯晓睿, 黄钊霞, 易夏玉, 等. NKT细胞在MRSA感染性肺炎中作用的初步研究[J]. 中国免疫学杂志, 2023, 39(9): 1803-1808. doi: 10.3969/j.issn.1000-484X.2023.09.003 HOU X R, HUANG Z X, YI X Y, et al. Preliminary study on role of NKT cells in MRSA infectious pneumonia[J]. Chinese Journal of Immunology, 2023, 39(9): 1803-1808. doi: 10.3969/j.issn.1000-484X.2023.09.003
[22]	ALMEIDA J S, CASANOVA J M, SANTOS-ROSA M, et al. Natural killer T-like cells: immunobiology and role in disease[J]. Int J Mol Sci, 2023, 24(3): 2743. DOI: 10.3390/ijms24032743.
[23]	LI J, YU T T, YAN H C, et al. T cells participate in bone remodeling during the rapid palatal expansion[J]. FASEB J, 2020, 34(11): 15327-15337. doi: 10.1096/fj.202001078R
[24]	FAVALORO E J, PASALIC L. Lupus anticoagulant testing during anticoagulation, including direct oral anticoagulants[J]. Res Pract Thromb Haemost, 2022, 6(2): e12676. DOI: 10.1002/rth2.12676.
[25]	DEVREESE K, DE GROOT P G, DE LAAT B, et al. Guidance from the scientific and standardization committee for lupus anticoagulant/antiphospholipid antibodies of the international society on thrombosis and haemostasis: update of the guidelines for lupus anticoagulant detection and interpretation[J]. J Thromb Haemost, 2020, 18(11): 2828-2839. doi: 10.1111/jth.15047
[26]	JIANG W, HU J W, HE X R, et al. Statins: a repurposed drug to fight cancer[J]. J Exp Clin Cancer Res, 2021, 40(1): 241. DOI: 10.1186/s13046-021-02041-2.