BACKGROUND: The intricate relationship between systemic immune-inflammation index (SII) and trimethylamine N-oxide (TMAO) in the peripheral blood and osteoporosis (OP) remains unclear. This study aims to investigate variations in the levels of SII and TMAO in the peripheral blood of overweight and obese patients, and examine the associations between these markers, bone mineral density (BMD), and the occurrence of osteoporotic fractures. METHODS: The study enrolled 765 patients aged ≥ 50 years with BMI ≥ 24 kg/m², dividing them into two groups based on visceral fat area (VFA): <
100 cm² and ≥100 cm². A corrected regression model analyzed the association of SII, TMAO, BMD, and osteoporotic fractures incidence in patients with central obesity. Receiver operator characteristic (ROC) curves assessed the predictive ability of SII and TMAO for OP screening. RESULTS: Baseline data showed that patients with VFA ≥ 100 cm² had lower whole body (WB) and lumbar spine (LS) BMD, but higher SII and TMAO levels compared to those with VFA <
100 cm² (p <
0.05). Particularly in the group with VFA ≥ 100 cm CONCLUSION: In overweight and obese patients, particularly those with a VFA ≥ 100 cm², peripheral blood SII and TMAO levels may serve as valuable biomarkers for the early diagnosis of OP, offering potential clinical utility in identifying high-risk individuals.