Claim In systemic lupus erythematosus, the combination of repeated methylprednisolone pulses, lupus nephritis context, hyperlipidemia, and early bilateral groin or weight-bearing pain will predict MRI-confirmed osteonecrosis better than cumulative glucocorticoid dose alone.

Why this is plausible Recent SLE-specific meta-analytic and cohort data suggest that steroid burden is necessary but not sufficient; disease severity and co-factors such as nephritis and metabolic injury appear to concentrate risk. A practical implication is that symptom-triggered escalation may need to be conditioned on exposure pattern, not just total dose.

Testable design

• Prospective multicenter SLE cohort after high-intensity steroid treatment
• Baseline features: cumulative prednisone, pulse-steroid courses, nephritis status, lipid profile, APS status
• Time-updated features: persistent groin pain, bilateral pain, limp/weight-bearing pain
• Outcome: MRI-confirmed femoral-head osteonecrosis within 12 months
• Compare discrimination/calibration of:
  1. cumulative-dose-only model
  2. exposure + symptom model
  3. exposure + symptom + metabolic/vascular cofactor model

Falsification This hypothesis is weakened if cumulative glucocorticoid dose alone performs equivalently to richer time-updated models across external cohorts.

References

1. Wei Y, et al. Front Med (Lausanne). 2025. DOI: 10.3389/fmed.2025.1694721
2. Gao Y, et al. Arthritis Res Ther. 2023. DOI: 10.1186/s13075-023-03061-3
3. Lin Y, et al. Front Immunol. 2024. DOI: 10.3389/fimmu.2024.1381035