Bioavailable Estradiol May Be an Important Determinant of Osteoporosis in Men: The MINOS Study1
P. Szulc,
F. Munoz,
B. Claustrat,
P. Garnero,
F. Marchand,
F. Duboeuf and
P. D. Delmas
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
epidemiologicalstudies have suggested an important role for estradiol
in bonemetabolism in men. In a cohort of 596 men, aged 51–85yr, 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, andsex
hormone-binding globulin]; and markers of bone turnover[serum
osteocalcin, bone alkaline phosphatase, N-terminal extensionpropeptide
of type I collagen, and ß-isomerized C-terminaltelopeptide of
collagen type I (ßCTX)], as well as urinaryexcretion of ßCTX and
deoxypyridinoline (DPyr). An age-relateddecrease was found for
bio-17ßE2 (r = -0.16; P <
0.001),free testosterone (r = -0.25; P <
0.001), free testosteroneindex (r = -0.32; P
< 0.001), and androstenedione (r = -0.22;P
< 0.001), but not for total 17ßE2 or total testosterone.
17ßE2and bio-17ßE2, but not other
hormones, were correlatedwith BMD after adjustment for age and body
weight. In men witha bio-17ßE2 level in the lowest
quartile, the averageBMD was lower than in men having a
bio-17ßE2 level inthe highest quartile by 6.6–8.7%
according to the siteof measurement, which corresponded to 0.45–0.65
SD. Inage- and body weight-adjusted models,
bio-17ßE2, but notother 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 menwith the lowest concentration
of bio-17ßE2 (first quartile),the concentrations of
markers of bone turnover were higher by11–35% (or 0.4–0.7
SD) than in men having the highestbio-17ßE2
level (upper quartile). In men in the lowestquartile for
bio-17ßE2 and in the highest quartile forurinary DPyr or
ßCTX, the BMD of total hip and that ofdistal forearm were 8% and
10% lower than in men in the highestquartile for
bio-17ßE2 and in the lowest quartile forDPyr or ßCTX.
In the age- and body weight-adjusted multipleregression models,
bio-17ßE2 contributed significantlyto the explanation
for the variability in all markers.
In summary, we found in a cross-sectional analysis of a cohortof men
that low levels of bio-17ßE2 are associated withhigh
bone turnover and low BMD. These data suggest that theage-related
decrease in bio-17ßE2 contributes to boneloss in elderly
men by increasing bone turnover. Low 17ßE2levels may be
an important risk factor for osteoporosis in men.
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