Previous studies have yielded inconsistent findings regarding the association between age at menopause and bone health, with limited exploration of potential mediating factors, particularly in the less-developed muti-ethnic regions of China. Our objective was to analyze the association between age at menopause and bone health among postmenopausal women in southwest China, while also examining the mediating effect of body mass index (BMI) and the moderating effect of years since menopause on this association. The analysis included a total of 15,352 naturally postmenopausal women obtained from the baseline data of the China Multi-Ethnic Cohort (CMEC) Study. Multiple linear regression was used for multivariate analysis. Mediation analysis was conducted to examine the mediating role of BMI in the association between age at menopause and bone health. A significant positive association was observed between age at menopause and bone health index (Quantitative ultrasound index, QUI). Specifically, with each year's delay in age at menopause, there was an increase of 0.260 (95% confidence interval (CI): 0.152-0.368) in QUI. Notably, women with later menopause (menopausal age ≥ 53 years) exhibited a higher QUI (β: 2.684, 95%CI: 1.503-3.865). Additionally, BMI partially mediated the relationship between age at menopause and QUI, accounting for 9.0% of the total effect, with an indirect effect coefficient β(95%CI) was 0.023(0.014, 0.032). Besides, it is worth mentioning that years since menopause moderated the association between age at menopause and bone health as well as the mediating effect of BMI. Naturally postmenopausal women with a later age at menopause demonstrate enhanced bone health. Maintaining a moderately high BMI, without progressing to overweight or obesity, may provide health benefits for postmenopausal women, especially for those with a longer duration since menopause.
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