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During recent years, experimental data, case reports, and epidemiological studies have suggested an important role for estradiol in bone metabolism in men. In a cohort of 596 men, aged 51-85 yr, we measured bone mineral density (BMD) of the lumbar spine, hip, total body, and forearm; serum levels of sex steroid hormones [total and free testosterone, total estradiol (17betaE(2)), bioavailable estradiol (bio-17betaE(2)), androstenedione, and sex hormone-binding globulin]; and markers of bone turnover [serum osteocalcin, bone alkaline phosphatase, N-terminal extension propeptide of type I collagen, and beta-isomerized C-terminal telopeptide of collagen type I (betaCTX)], as well as urinary excretion of betaCTX and deoxypyridinoline (DPyr). An age-related decrease was found for bio-17betaE(2) (r = -0.16; P &lt; 0.001), free testosterone (r = -0.25; P &lt; 0.001), free testosterone index (r = -0.32; P &lt; 0.001), and androstenedione (r = -0.22; P &lt; 0.001), but not for total 17betaE(2) or total testosterone. 17betaE(2) and bio-17betaE(2), but not other hormones, were correlated with BMD after adjustment for age and body weight. In men with a bio-17betaE(2) level in the lowest quartile, the average BMD was lower than in men having a bio-17betaE(2) level in the highest quartile by 6.6-8.7% according to the site of measurement, which corresponded to 0.45-0.65 SD. In age- and body weight-adjusted models, bio-17betaE(2), but not other hormones, was negatively correlated with bone markers (e.g., osteocalcin: r = -0.14; P &lt; 0.001; urinary betaCTX: r = -0.20; P = 0.0001; DPyr: r = -0.14; P &lt; 0.001). In men with the lowest concentration of bio-17betaE(2) (first quartile), the concentrations of markers of bone turnover were higher by 11-35% (or 0.4-0.7 SD) than in men having the highest bio-17betaE(2) level (upper quartile). In men in the lowest quartile for bio-17betaE(2) and in the highest quartile for urinary DPyr or betaCTX, the BMD of total hip and that of distal forearm were 8% and 10% lower than in men in the highest quartile for bio-17betaE(2) and in the lowest quartile for DPyr or ssCTX. In the age- and body weight-adjusted multiple regression models, bio-17betaE(2) contributed significantly to the explanation for the variability in all markers. In summary, we found in a cross-sectional analysis of a cohort of men that low levels of bio-17betaE(2) are associated with high bone turnover and low BMD. These data suggest that the age-related decrease in bio-17betaE(2) contributes to bone loss in elderly men by increasing bone turnover. Low 17betaE(2) levels may be an important risk factor for osteoporosis in men.

Bioavailable Estradiol May Be an Important Determinant of Osteoporosis in Men: The MINOS Study1

Bioavailable Estradiol May Be an Important Determinant of Osteoporosis in Men: The MINOS Study¹