Identification of Potential Core Genes in Medication‐Related Osteonecrosis of the Jaw via Bioinformatics Analysis

Background Medication‐related osteonecrosis of the jaw (MRONJ) is a severe complication associated with antiresorptive or antiangiogenic therapy, yet its molecular mechanisms remain poorly understood. This study aimed to identify potential core genes involved in MRONJ pathogenesis through integrative bioinformatics analysis. Methods GSE7116 dataset (PBMC samples from 11 MRONJ and 10 non‐MRONJ multiple myeloma patients on bisphosphonates) was analyzed. DEGs were identified using GEO2R. Functional enrichment, PPI network, hub gene identification, ROC‐based diagnostic evaluation, and independent qRT‐PCR validation were performed. Results 241 DEGs (212 down, 29 up) were identified, enriched in immune/inflammatory responses and NOD‐like receptor/NF‐κB pathways. Ten hub genes ( TNF , ACTB , IL1B , JUN , CXCL8 , CXCR4 , PTPRC , IL1A , HSP90AB1 , RHOA ) were identified. Four of them ( HSP90AB1 , RHOA , CXCL8 , IL1B ) showed high diagnostic accuracy (AUC 0.864–0.936) and were validated by qRT‐PCR. Conclusion This integrative bioinformatics analysis, combined with ROC evaluation and experimental qPCR validation, identifies immune‐ and inflammation‐related hub genes as central to MRONJ pathogenesis. A four‐gene signature ( HSP90AB1 , RHOA , CXCL8 , IL1B ) shows high diagnostic accuracy (AUC 0.864–0.936) and is proposed as a peripheral blood‐based diagnostic panel. The widespread downregulation of inflammatory genes in PBMCs suggests systemic immunosuppression rather than overt inflammation, offering new insights for immunomodulatory strategies.