Single-Cell RNA Sequencing Reveals Distinct Cellular and Molecular Features of Steroid-Induced Osteonecrosis of the Femoral Head Compared to Alcohol-Induced Osteonecrosis and Hip Osteoarthritis

Steroid-induced osteonecrosis of the femoral head shows a neutrophil-predominant immune profile with an elevated innate-to-adaptive immune cell ratio versus alcohol-induced ONFH and hip OA.

• Why it matters: The mechanisms behind ONFH after glucocorticoids versus alcohol are unclear, limiting etiology-specific treatment strategies.
• What they did: Single-cell RNA sequencing of femoral head specimens from patients undergoing total hip arthroplasty compared steroid-induced ONFH, alcohol-induced ONFH, and hip osteoarthritis, assessing immune and stromal cell states.
• The result: Steroid-induced ONFH is linked to impaired T cell maturation (more naive T cells, fewer mature CD4+ and CD4+ memory T cells), increased exhausted/dysfunctional CD8+ T cells versus alcohol-induced ONFH, and more pericytes, endothelial cells, and osteogenic mesenchymal cells versus both comparator conditions.

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