Free Testosterone Is a Positive, Whereas Free Estradiol Is a Negative, Predictor of Cortical Bone Size in Young Swedish Men: The GOOD Study

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Abstract
In this study, we evaluated the predictive roles of sex steroids for skeletal parameters in young men (n = 1068) at the age of peak bone mass. Serum free estradiol was a negative predictor, whereas free testosterone and SHBG were positive predictors of cortical bone size. Introduction: Previous studies have shown that free estradiol in serum is an independent predictor of areal BMD (aBMD) in elderly men. The aim of this study was to determine whether sex steroids are predictors of volumetric BMD (vBMD) and/or size of the trabecular and cortical bone compartments in young men at the age of peak bone mass. Materials and Methods: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study consists of 1068 men, 18.9 ± 0.6 years of age. Serum levels of testosterone, estradiol, and sex hormone binding globulin (SHBG) were measured, and free levels of testosterone and estradiol were calculated. The size of the cortical bone and the cortical and trabecular vBMDs were measured by pQCT. Results: Regression models including age, height, weight, free estradiol, and free testosterone showed that free estradiol was an independent negative predictor of cortical cross-sectional area (tibia β = −0.111, p < 0.001; radius β = −0.125, p < 0.001), periosteal circumference, and endosteal circumference, whereas it was a positive independent predictor of cortical vBMD (tibia β = 0.100, p < 0.003; radius β = 0.115, p = 0.001) in both the tibia and radius. Free testosterone was an independent positive predictor of cortical cross-sectional area (tibia β = 0.071, p = 0.013; radius β = 0.064, p = 0.039), periosteal circumference, and endosteal circumference in both the tibia and radius. Neither cortical nor trabecular vBMD was associated with free testosterone. SHBG was an independent positive predictor of parameters reflecting the size of the cortical bone, including cross-sectional area (β = 0.078, p = 0.009), periosteal circumference, and endosteal circumference. Conclusions: Free estradiol is a negative, whereas free testosterone is a positive, predictor of cortical bone size in young men at the age of peak bone mass. These findings support the notion that estrogens reduce, whereas androgens increase, cortical bone size, resulting in the well-known sexual dimorphism of cortical bone geometry.

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