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Meta-analysis of factors for osteonecrosis in systemic lupus erythematosus: integration of comprehensive literatures
Rui-Cen Li1, Lin-Chong Su2,3, An-Fang Huang4
1Health Management Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
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.