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

INSERM, U-403; and Hôpital Neuro-Cardiologique (B.C.), 69437 Lyon, France; and Société de Secours Minière de Bourgogne (F.M.), 71300 Montceau les Mines, France

Address all correspondence and requests for reprints to: Prof. Pierre D. Delmas, INSERM, U- 403, Hôpital Edouard Herriot, place d’Arsonval, 69437 Lyon, France. E-mail: delmas{at}lyon151.inserm.fr

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 (17ßE₂), bioavailable estradiol (bio-17ßE₂), 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 ß-isomerized C-terminal telopeptide of collagen type I (ßCTX)], as well as urinary excretion of ßCTX and deoxypyridinoline (DPyr). An age-related decrease was found for bio-17ßE₂ (r = -0.16; P < 0.001), 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 17ßE₂ or total testosterone. 17ßE₂ and bio-17ßE₂, but not other hormones, were correlated with BMD after adjustment for age and body weight. In men with a bio-17ßE₂ level in the lowest quartile, the average BMD was lower than in men having a bio-17ßE₂ 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-17ßE₂, but not other hormones, was negatively correlated with bone markers (e.g., osteocalcin: r = -0.14; P < 0.001; urinary ßCTX: r = -0.20; P = 0.0001; DPyr: r = -0.14; P < 0.001). In men with the lowest concentration of bio-17ßE₂ (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-17ßE₂ level (upper quartile). In men in the lowest quartile for bio-17ßE₂ and in the highest quartile for urinary DPyr or ßCTX, the BMD of total hip and that of distal forearm were 8% and 10% lower than in men in the highest quartile for bio-17ßE₂ and in the lowest quartile for DPyr or ßCTX. In the age- and body weight-adjusted multiple regression models, bio-17ßE₂ 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-17ßE₂ are associated with high bone turnover and low BMD. These data suggest that the age-related decrease in bio-17ßE₂ contributes to bone loss in elderly men by increasing bone turnover. Low 17ßE₂ levels may be an important risk factor for osteoporosis in men.

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