# Population characteristics, glucocorticoid dosage, and risk factors for osteonecrosis of the femoral head in systemic lupus erythematosus: a Systematic Review and meta-analysis

## TL;DR

This study identifies risk factors for bone damage in lupus patients, showing that high initial steroid doses and certain health conditions increase the risk.

## Contribution

The study clarifies that short-term high-dose steroid use, not cumulative dose, is a key risk factor for bone damage in lupus patients.

## Key findings

- Patients with SLE who developed ONFH had a younger age at diagnosis and higher SLEDAI scores.
- Short-term high-dose glucocorticoid exposure significantly increases ONFH risk, while cumulative dose does not.
- Vasculitis, hypertension, and thrombocytopenia are independent risk factors for ONFH in SLE patients.

## Abstract

Osteonecrosis 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.

To 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.

We 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.

Thirty-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.

Patients 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.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420251084371, identifier CRD420251084371.