Epidemiological studies investigating the association between flavonoid intake and bone mineral density (BMD) draw inconsistent conclusions. Our study aims to investigate the association between flavonoid intake and BMD and osteoporosis and the mediating role of composite dietary antioxidant index (CDAI) in their relationship using data from the National Health and Nutrition Examination Survey (NHANES). The study assessed the relationship between flavonoid intake and femur BMD and osteoporosis in 10,225 individuals from NHANES 2007-2010 and 2017-2018. Multivariable linearregression analyses were used to detect the association between flavonoid intake and femur BMD in adult Americans. Restricted cubic splines (RCS) were used to examine the nonlinear relationship between flavonoid intake and their subclasses and osteoporosis risk in individuals 20years or older. We explored the mediating role of CDAI in the association between flavonoid intake and BMD. In fully adjusted multivariable regression analyses, compared with people in the first quartile, people in the fourth quartile of total flavonoid intake have a higher BMD at total femur (0.013, 95% CI: 0.004, 0.022, P = 0.001), femur neck (0.010, 95% CI: 0.004, 0.017, P = 0.001), trochanter (0.010, 95% CI: 0.004, 0.017, P = 0.001), and intertrochanter (0.012, 95% CI: 0.003, 0.020, P = 0.006). The positive relationship between flavonoid intake and femur BMD was present in both sexes. Furthermore, we found that people in the fourth quartile of total flavonoid intake have a lower risk of osteoporosis compared with the first quartile (OR = 0.686, 95% CI: 0.528-0.890, P = 0.005). RCS found a linear inverse relationship between total flavonoid intake and osteoporosis in individuals ≥ 20years (Overall P = 0.015, nonlinear P = 0.086). Moreover, CDAI partially mediates the association of total flavonoid intake with femur BMD. Our findings suggest that higher flavonoid intake is associated with higher BMD and lower risk of osteoporosis in Americans. Furthermore, we found distinct associations between different flavonoid subclasses and osteoporosis risk. More studies with stronger evidence are needed to explore the causal association between flavonoid intake and bone health and their underlying mechanisms.
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