系统性红斑狼疮骨坏死因素的Meta分析：综合文献与多中心数据库的整合

摘要(中文译文)

骨坏死（ON）是系统性红斑狼疮（SLE）患者中常见且严重的并发症。然而，SLE-ON的病因及发病机制尚未完全阐明。本研究旨在探讨与SLE-ON相关的因素，为早期预防和控制提供依据。研究全面检索了PubMed、Ovid Medline、Web of Science、Embase、Cochrane Library、CNKI、万方数据和维普信息数据库截至2025年10月31日的相关文献。根据纳入和排除标准，共审查了3，051项研究，并采用纽卡斯尔-渥太华量表（NOS）评估每项研究的质量。采用Meta分析方法探讨与SLE-ON相关因素的关联。最终共有64项研究纳入Meta分析。在临床特征方面，神经精神性狼疮（OR=1.652）、高脂血症（OR=1.358）、口腔溃疡（OR=1.319）、胸膜炎（OR=2.225）、颧部皮疹（OR=1.311）、血管炎（OR=2.638）、浆膜炎（OR=1.514）、血液系统受累（OR=1.190）、雷诺现象（OR=1.604）、血栓性静脉炎（OR=1.856）和关节炎（OR=1.256）等因素与SLE-ON风险呈正相关。在实验室特征方面，蛋白尿（OR=1.635）、抗磷脂抗体（OR=1.450）、ESR升高（OR=1.623）、白细胞减少（OR=1.317）和ACL（OR=1.657）也与SLE-ON风险呈正相关。有趣的是，抗SSA抗体（OR=0.805）和抗SSB抗体（OR=0.764）与SLE-ON易感性呈负相关。环磷酰胺的使用（OR=1.869）和激素冲击治疗（OR=1.829）与SLE-ON的发生呈正相关。此外，较年轻的年龄（SMD=-0.175）和发病年龄（SMD=-0.426）与SLE-ON的发生显著相关。共有32项因素与SLE合并骨坏死相关，包括SLE患者的临床特征、实验室特征、药物使用和基本信息。值得注意的是，环磷酰胺/激素冲击治疗与SLE-ON风险之间的关联可能受到基础疾病严重程度的混杂影响，因此这些结果应谨慎解读。对这些可改变的危险因素进行针对性监测和干预，尤其是优化激素冲击治疗和环磷酰胺的使用以及早期骨质疏松筛查，并结合基于抗SSA/SSB抗体状态的风险分层，可能有助于降低SLE-ON风险并改善SLE患者的临床管理。

Abstract

Osteonecrosis (ON) is a prevalent and severe complication in patients with systemic lupus erythematosus (SLE). However, the etiology and mechanism of SLE-ON have not been fully elucidated. This study aims to investigate the factors related to SLE-ON and provide a basis for early prevention and control. A comprehensive search of relevant literatures was conducted from PubMed, Ovid Medline, Web of Science, Embase, Cochrane Library, CNKI, Wanfang Data, and VIP Information databases up to 31 October 2025. According to the inclusion and exclusion criteria, 3,051 studies were examined, and quality of each study was assessed using the Newcastle-Ottawa scale (NOS). Meta-analysis methods discussed the association of the factors related to SLE-ON. A total of 64 studies were finally included in the meta-analysis. For clinical features, factors such as neuropsychiatric lupus (OR = 1.652), hyperlipidemia (OR = 1.358), oral ulcers (OR = 1.319), pleuritis (OR = 2.225), malar rash (OR = 1.311), vasculitis (OR = 2.638), serositis (OR = 1.514), hematologic involvement (OR = 1.190), Reynaud's phenomenon (OR = 1.604), thrombophlebitis (OR = 1.856), and arthritis (OR = 1.256) were positively related to SLE-ON risk. For laboratory features, proteinuria (OR = 1.635), antiphospholipid antibody (OR = 1.450), elevated ESR (OR = 1.623), leukopenia (OR = 1.317), and ACL (OR = 1.657) were positively related to SLE-ON risk as well. Interestingly, the anti-SSA antibody (OR = 0.805) and anti-SSB antibody (OR = 0.764) were negatively related to SLE-ON susceptibility. Usage of cyclophosphamide (OR = 1.869) and steroid pulse therapy (OR = 1.829) was positively correlated with occurrence of SLE-ON. Furthermore, younger age (SMD=-0.175) and the age at onset (SMD=-0.426) significantly related to developing of SLE-ON. A total of 32 factors including clinical, laboratory features, drug usage, and basic information in SLE patients were related to SLE complicated with osteonecrosis. Of note, the association between cyclophosphamide/steroid pulse therapy and SLE-ON risk may be confounded by underlying disease severity, so these results should be interpreted cautiously. Targeted monitoring and intervention of these modifiable risk factors, especially optimized steroid pulse therapy and cyclophosphamide use and early osteoporosis screening, combined with risk stratification based on anti-SSA/SSB antibody status, may help reduce SLE-ON risk and improve clinical management of SLE patients.

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