Dietary riboflavin (vitamin B2) intake and osteoporosis in U.S. female adults: unveiling of association and exploration of potential molecular mechanisms

A total of 4, 241 female participants from four NHANES cycles were included in this study. After multivariate adjustment, the intake of vitamin B2 was beneficially associated with reduced risk for femur osteoporosis (OR_{Q4 vs. Q1}=0.613; 95%CI: 0.454-0.829). A higher intake of vitamin B2 (quartile 4) was significantly correlated with decreased risk of reduced femoral BMD levels, with the β being 0.020 (95%CI: 0.007-0.033), 0.015 (95%CI: 0.002-0.027), 0.020 (95%CI: 0.009-0.031) and 0.022 (95%CI: 0.006-0.037) for the BMD of total femur, femoral neck, trochanter, and intertrochanter, respectively (all P value < 0.05). Covariate total MET was found to modify the association between vitamin B2 intake and osteoporosis (P interaction = 0.0364), with the aforementioned relationship being more pronounced in the subgroup of insufficiently active individuals. Furthermore, RCS analysis revealed that vitamin B2 intake was positively and linearly associated with reduced risk for femoral OP and increased BMD levels of total femur, trochanter and intertrochanter, while positively and nonlinearly correlated with increased BMD level of femoral neck. Additionally, the association between vitamin B2 intake, osteoporosis and BMD levels was mediated by ALP, with a mediation proportion of 12.43%, 7.58%, 12.17%, 7.64%, and 6.99% for OP, total femur, femoral neck, trochanter, and intertrochanter BMD, respectively. Finally, network pharmacology analysis indicated that vitamin B2 regulating bone health mainly through pathways like HIF-1 signaling pathway, longevity regulating pathway, p53 signaling pathway, etc. CONCLUSIONS: Higher intake of vitamin B2 is positively associated with reduced risks for femoral osteoporosis and bone loss. Vitamin B2 may represent a modifiable lifestyle factor for the prevention and management of osteoporosis.