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Abstract

Osteoporosis is a silent disease that is typically not diagnosed until after a fracture has occurred. Identifying biomarkers routinely collected by physicians can serve as a simple and effective screening approach to detect osteoporosis before debilitating fractures occur. The ratio of total estradiol to total testosterone (ET x10)/TT has been proposed as a biomarker associated with bone mineral density (BMD). To further improve predictive power, we propose a ratio of estradiol to free testosterone (ET/TF), rather than total, to account for the difference in hormone bioavailability. PURPOSE: The present analysis compares the association between sex hormone predictors and BMD at two primary fracture sites in US adults over age 50. METHODS: NHANES 2013-2014 cycle was analyzed in R Studio, using univariate linear regression to investigate the relationships between free and total sex hormone levels (estradiol, testosterone), as well as their ratios (free androgen index (FAI), free estrogen index (FEI), ETx10/TT, ET/TF) with femoral neck and lumbar spine BMD in men, pre-menopausal women, and post-menopausal women. Fully standardized regression coefficients were calculated to allow for direct comparison of effect sizes between the predictor and outcome. RESULTS: In men, free estradiol demonstrated the largest association (β=0.111, p= 0.015) with BMD at the femoral neck. At the lumbar spine, ETx10/TT demonstrated the strongest association (β=0.203, p= 0.014) with BMD. In pre-menopausal women, none of the variables were significantly associated with BMD at the femoral neck. At the lumbar spine, FEI displayed the strongest association with BMD (β= 0.222, p=0.032). ETx10/TT demonstrated a stronger association (β= 0.209, p=0.032) with BMD than ET/TF (β= 0.181, p=0.049). In post-menopausal women, none of the variables were significantly associated with BMD at the femoral neck or lumbar spine. CONCLUSION: Standardized effect sizes for ET/TF were consistently smaller than ETx10/TT, suggesting a weaker association with BMD at both sites. ETx10/TT predicts BMD as well as estradiol-related measures (total, free, FEI) at the lumbar spine in all groups; interestingly, this relationship was more robust in men. Future research should evaluate the true predictive value of ETx10/TT for lumbar spine BMD in prospective longitudinal and controlled cohorts.

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