Alterations in ferroptosis-associated biomarkers and immune dysregulation in diabetic osteoporotic patients

BACKGROUND: Ferroptosis has recently been identified as a potential mechanism linking metabolic dysfunction to diabetic osteoporosis (DOP). Nevertheless, clinical evidence regarding ferroptosis-associated biomarkers in DOP remains limited. METHODS: In this case-control study, markers of glucose metabolism, iron homeostasis, oxidative stress, antioxidant status, inflammation, and ferroptosis were assessed in 185 participants, including 110 patients with DOP and 75 controls. RESULTS: Patients with DOP showed significant metabolic alterations, including increased fasting glucose, insulin, HbA1c, HOMA-IR, serum iron, ferritin, PTGS2, and ACSL4 levels. Oxidative stress markers (MDA, TBARS, and GSSG) and inflammatory cytokines (IL-6, IL-1β, TNF-α, and IL-10) were also increased, whereas antioxidant markers (GSH, TAC, and GPX4) were decreased. Ferritin and HOMA-IR were independently associated with PTGS2 levels. PTGS2 and ferritin demonstrated good exploratory discriminatory performance between patients with DOP and controls, while the combined biomarker model showed the highest exploratory discriminatory performance. CONCLUSION: Patients with DOP revealed alterations to metabolic state, oxidative balance, antioxidant defenses, inflammatory signaling, and systemic iron homeostasis. The exploratory ROC results indicate discrimination between patients with DOP and controls; however, DOP-specific diagnostic performance cannot be determined due to the absence of T2DM-only and osteoporosis-only comparator groups.