Multifocal Glucocorticoid-Associated Osteonecrosis: Clinical Characteristics and Systemic Molecular Features

Background: Multifocal osteonecrosis involving three or more anatomical sites is an uncommon but severe manifestation of glucocorticoid-associated osteonecrosis and may be associated with systemic clinical backgrounds. This study investigated the clinical characteristics and exploratory serum proteomic profiles of multifocal osteonecrosis using clinical and proteomic analyses. Methods: We analyzed 107 patients who underwent surgery for osteonecrosis of the femoral head between 2019 and 2024. Whole-body MRI was used to detect multifocal lesions. Patients were classified into glucocorticoid-related osteonecrosis of the femoral head (GO) and multifocal glucocorticoid-related osteonecrosis (MGO). Clinical variables were compared, and multivariate logistic regression identified clinical factors associated with multifocal osteonecrosis. Serum proteomic profiling using nanoLC-MS/MS was performed as an exploratory analysis to compare protein expression among GO, MGO, and osteoarthritis controls. Results: Multifocal osteonecrosis was identified in 31 patients (29.0%). Patients with MGO were younger (42.6 vs. 50.9 years, p = 0.021) and had higher glucocorticoid doses (59.5 vs. 48.5 mg, p = 0.005). Hematologic diseases (OR 14.51, 95% CI 3.42-86.69, p < 0.001) and skin manifestations (OR 3.17, 95% CI 1.05-10.44, p = 0.046) were independently associated with multifocal osteonecrosis. Exploratory proteomic analysis showed protein expression patterns related to fibrinolysis, coagulation, inflammation, and vascular homeostasis in MGO. Conclusions: Multifocal osteonecrosis was associated with systemic clinical backgrounds and showed exploratory vascular- or coagulation-related proteomic patterns within glucocorticoid-associated osteonecrosis.