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

Abstract Background Osteoporosis characterized by deteriorating bone loss is becoming one of the serious health problems globally. Vitamin B2, also known as riboflavin, exhibiting multiple prominent physiological traits such as antioxidant effects, reducing lipid peroxidation and regulating glutathione redox cycle, allows it to be a potential agent to improve bone loss. However, the relationship between dietary vitamin B2 intake and osteoporosis remains unelucidated. The objective of this study was to explore the association between the dietary intake of vitamin B2 and bone loss in the U.S. female adults using the National Health and Nutrition Examination Survey (NHANES) database. Methods Female participants with complete information on dietary vitamin B2 intake, dual-energy X-ray absorptiometry, and other essential covariates from NHANES database were included in the current study. Multivariable logistic regression and linear regression analyses were conducted to assess the relationships of dietary vitamin B2 intake with osteoporosis and bone mineral density (BMD) levels, respectively. Subgroup analyses, interaction tests, and restricted cubic spline (RCS) regression analyses were further used to verify the stability, robustness and potential nonlinearity of the association. Mediation analysis was performed to probe the role of serum alkaline phosphatase (ALP) in the aforementioned relationship, and the network pharmacology analysis was also conducted to determine the potential pathways and key targets for vitamin B2 regulating bone health. Results 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 (ORQ4 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.