S. Vedi et al., Bone remodeling and structure in postmenopausal women treated with long-term, high-dose estrogen therapy, OSTEOPOR IN, 10(1), 1999, pp. 52-58
Conventional hormone replacement therapy preserves bone mass predominantly
by reducing bone turnover but does not exert significant anabolic skeletal
effects. In contrast, high doses of estrogen have been shown to increase bo
ne formation in animals and we have recently reported high bone mineral den
sity values in women treated long-term with estradiol implant therapy. The
aim of this study was to investigate the mechanisms by which high doses of
estrogen may increase bone mass in postmenopausal women. Iliac crest biopsi
es were obtained from 12 women who had received long-term treatment with es
tradiol implants (at least 14 years), on demand, following hysterectomy and
bilateral salpingo-oophorectomy. Indices of bone turnover, remodeling bala
nce and cancellous bone structure were assessed by image analysis and compa
red with those of premenopausal women. Mean wall width was significantly hi
gher in women treated with estradiol therapy than in premenopausal women (4
4.8 +/- 4.8 vs 38.8 +/- 2.8 mu m; mean +/- SD; p = 0.001) and eroded cavity
area was significantly lower in the implant-treated women (3612 +/- 956 vs
5418 +/- 1404 mu m; p = 0.001). Bone formation rate at tissue level and ac
tivation frequency were lower in the women treated with implants, although
the differences were not statistically significant. Indices of cancellous b
one structure were generally similar between the two groups. These results
provide the first direct evidence that high-dose estrogen therapy produces
anabolic skeletal effects in postmenopausal women and indicate that these a
re achieved by stimulation of osteoblastic activity.