Background Changes in sex hormones are thought to play an important role in bone health in postmenopausal women. Our aim in this study was to evaluate the association between levels of estradiol (E2), which is the most potent endogenous estrogen, and sex hormone binding globulin (SHBG) and bone mineral density (BMD) among postmenopausal women, 40–59 years of age. Methods Using data from the National Health and Nutrition Examination Survey 2013–2016, we performed weighted multivariable linear regression models to evaluate the associations between serum levels of E2 and SHBG and lumbar BMD. A weighted generalized additive model and smooth curve fitting were used to address potential nonlinearity. Results A total of 608 postmenopausal women were included in the analysis. The serum E2 level was positively associated with lumbar BMD, after adjusting for other covariates (β 0.65; 95% confidence interval (CI) 0.38–0.93). An inverted U-shaped association between the serum E2 level and lumbar BMD was further identified, with the point of inflection at an E2 level of 70 pg/mL. There was no significant association between the SHBG level and lumbar BMD (β 0.01; 95% CI − 0.30 to 0.31). However, the association between these two variables was U-shaped, with the point of inflection at an SHBG level of 65 nmol/L. Conclusions Based on our findings, it may be beneficial to appropriately increase serum E2 levels to promote bone health in postmenopausal women with low estrogen levels. Considering the inverted U-shaped association, an excessive E2 level may be harmful to BMD. In addition, increasing the SHBG level to within the normal range (65–144 nmol/L) may be considered.

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