Sex-Specific Association Between Serum SOD Activity and Osteoporosis in Type 2 Diabetes: A Cross-Sectional Study with Functional Validation

Background/Objectives: Oxidative stress is closely tied to diabetic bone disorders. Superoxide dismutase (SOD) is a key antioxidant enzyme, yet its sex-specific link with osteoporosis in type 2 diabetes mellitus (T2DM) remains unclear. This study aimed to investigate this association and explore its potential biological mechanism. Methods: A retrospective cross-sectional study was performed on 2023 T2DM patients (1137 males, 886 females) grouped by bone mineral density (BMD). Multivariate logistic regression was used, and in vitro experiments validated SOD3’s effect on osteoclast differentiation. Results: After adjustment for potential confounders, higher serum SOD activity (>135 U/mL) was independently associated with approximately 50% lower odds of prevalent osteoporosis at the lumbar spine and femoral neck in women, whereas no significant association was observed in men. Recombinant SOD3 inhibited osteoclast differentiation in a concentration-dependent way. Conclusions: Higher serum SOD activity was independently associated with a lower prevalence of osteoporosis in women with T2DM. Serum SOD activity may serve as a potential biomarker associated with osteoporosis in this population. These findings provide new insights into the relationship between oxidative stress and diabetic bone disease and warrant validation in prospective studies.