Bioavailable estradiol may be an important determinant of osteoporosis in men: The MINOS study

During recent years, experimental data, case reports, and epidemiological s tudies 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 densi ty (BMD) of the lumbar spine, hip, total body, and forearm; serum levels of sex steroid hormones [total and free testosterone, total estradiol (17 bet aE(2)), bioavailable estradiol (bio-17 betaE(2)), androstenedione, and sex hormone-binding globulin]; and markers of bone turnover [serum osteocalcin, bone alkaline phosphatase, N-terminal extension propeptide of type I colla gen, and beta -isomerized C-terminal telopeptide of collagen type I (beta C TX)], as well as urinary excretion of beta CTX and deoxypyridinoline (DPyr) . An age-related decrease was found for bio-17 betaE(2) (r = -0.16; P < 0.0 01), free testosterone (r = -0.25; P < 0.001), free testosterone index (r = -0.32; P < 0.001), and androstenedione (r = -0.22; P < 0.001), but not for total 17 betaE(2) or total testosterone. 17 betaE(2) and bio-17 betaE(2), but not other hormones, were correlated with BMD after adjustment for age a nd body weight. In men with a bio-17 betaE(2) level in the lowest quartile, the average BMD was lower than in men having a bio-17 betaE(2) level in th e 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- 17 betaE(2), but not other hormones, was negatively correlated with bone ma rkers (e.g., osteocalcin: r = -0.14; P < 0.001; urinary <beta>CTX: r = -0.2 0; P = 0.0001; DPyr: r = -0.14; P < 0.001). In men with the lowest concentr ation of bio-17<beta>E-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-17 betaE(2) level (upper quartile). In men in the lowest quart ile for bio-17 betaE(2) and in the highest quartile for urinary DPyr or bet a CTX, the BMD of total hip and that of distal forearm were 8% and 10% lowe r than in men in the highest quartile for bio-17 betaE(2) and in the lowest quartile for DPyr or beta CTX. In the age- and body weight-adjusted multip le regression models, bio-17 betaE(2) contributed significantly to the expl anation 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-17 betaE(2) are associated with high bone turnover and lo w BMD. These data suggest that the age-related decrease in bio-17 betaE(2) contributes to bone loss in elderly men by increasing bone turnover. Low 17 betaE(2) levels may be an important risk factor for osteoporosis in men.