Data Sheet 1_Population characteristics, glucocorticoid dosage, and risk factors for osteonecrosis of the femoral head in systemic lupus erythematosus: a Systematic Review and meta-analysis.pdf

BackgroundOsteonecrosis of the femoral head (ONFH) is a severe complication of systemic lupus erythematosus (SLE). However, the demographic characteristics, glucocorticoids (GCs) risks, and other contributing factors remain debated.
ObjectiveTo elucidate the population characteristics, GCs-related risks, and other risk factors for ONFH in patients with SLE through a systematic review and meta-analysis, thereby enhancing the clinical identification of high-risk populations and optimizing GCs therapy strategies in SLE.
MethodsWe searched seven databases, from their inception until July 2025 for relevant cohort and case-control studies. The quality of included studies was assessed using the Newcastle-Ottawa Scale. Meta-analysis was performed using RevMan 5.3.
ResultsThirty-five studies involving 11,356 participants were included. Regarding population characteristics, patients with SLE who developed ONFH had a significantly younger age at diagnosis (SMD = -0.19, P < 0.00001) and higher SLEDAI scores (SMD = 0.21, P = 0.002). Among metabolic and immune indicators, elevated triglycerides (SMD = 0.21, P = 0.02), decreased high-density lipoprotein cholesterol (SMD = -0.22, P = 0.03), and positive antiphospholipid antibodies (OR = 2.00, P = 0.04) were associated with ONFH occurrence. Regarding GC therapy, pulse steroid therapy (OR = 2.02, P < 0.00001), an initial dose >60 mg/day (OR = 4.19, P < 0.0001), a maximum daily dose >50 mg (SMD = 0.42, P = 0.0002), and higher average daily GC intake (SMD = 0.32, P = 0.004) significantly increased ONFH risk. In contrast, cumulative GC dose showed no significant association (P = 0.14). Furthermore, vasculitis (OR = 3.17, P < 0.00001), hypertension (OR = 1.48, P = 0.02), Raynaud’s phenomenon (OR = 1.60, P = 0.0003), thrombocytopenia (OR = 1.69, P = 0.007), and arthritis (OR = 1.88, P = 0.006) were identified as independent risk factors.
ConclusionPatients with SLE at high risk for ONFH exhibit distinct characteristics. Short-term high-dose GC exposure, rather than cumulative dose, constitutes the core medication-related risk. Enhanced imaging screening and comprehensive, multi-factorial prevention strategies are warranted, particularly for patients receiving high initial doses or pulse therapy. Clinical management should focus on optimizing GC regimens in these high-risk individuals to minimize the occurrence of ONFH.
Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420251084371, identifier CRD420251084371.

背景
股骨头缺血性坏死（Osteonecrosis of the femoral head, ONFH）是系统性红斑狼疮（systemic lupus erythematosus, SLE）的严重并发症之一，但目前关于其人群特征、糖皮质激素（glucocorticoids, GCs）相关风险及其他致病因素仍存在争议。

研究目的
本研究旨在通过系统评价与荟萃分析，阐明SLE患者发生ONFH的人群特征、GCs相关风险及其他危险因素，以期提升临床对高危人群的识别效率，并优化SLE患者的GCs治疗方案。

研究方法
我们检索了7个数据库自建库至2025年7月的相关队列研究与病例对照研究。采用纽卡斯尔-渥太华量表（Newcastle-Ottawa Scale）对纳入研究的质量进行评价，并使用RevMan 5.3软件完成荟萃分析。

研究结果
最终纳入35项研究，共涉及11356名受试者。在人群特征方面，发生ONFH的SLE患者诊断时年龄显著更年轻（标准化均数差SMD=-0.19，P<0.00001），且SLE疾病活动指数（SLEDAI）评分更高（SMD=0.21，P=0.002）。在代谢与免疫指标层面，甘油三酯升高（SMD=0.21，P=0.02）、高密度脂蛋白胆固醇降低（SMD=-0.22，P=0.03）以及抗磷脂抗体阳性（比值比OR=2.00，P=0.04）均与ONFH的发生相关。在GCs治疗方面，冲击剂量激素治疗（OR=2.02，P<0.00001）、初始日剂量>60mg（OR=4.19，P<0.0001）、最大日剂量>50mg（SMD=0.42，P=0.0002）以及更高的平均每日GCs摄入量（SMD=0.32，P=0.004）均显著升高ONFH发生风险；而累积GCs剂量与ONFH风险无显著关联（P=0.14）。此外，血管炎（OR=3.17，P<0.00001）、高血压（OR=1.48，P=0.02）、雷诺现象（Raynaud’s phenomenon，OR=1.60，P=0.0003）、血小板减少症（OR=1.69，P=0.007）及关节炎（OR=1.88，P=0.006）被确定为独立危险因素。

研究结论
ONFH高危SLE患者具有独特的临床特征。短期大剂量GCs暴露而非累积剂量，是核心的药物相关危险因素。临床应加强影像学筛查，并制定综合多因素预防策略，尤其针对接受高初始剂量或冲击治疗的患者。临床管理应聚焦于优化此类高危人群的GCs给药方案，以尽可能降低ONFH的发生风险。

系统评价注册信息
本系统评价已在PROSPERO平台注册，注册链接：https://www.crd.york.ac.uk/PROSPERO/view/CRD420251084371，注册号为CRD420251084371。