Tamoxifen Inhibits Osteoclast-Mediated Resorption of Trabecular Bone in Ovarian Hormone-Deficient Rats*

Abstract

The effects of the nonsteroidal antiestrogen tamoxifen were determined on trabecular bone mass in the proximal tibial metaphysis of intact and ovariectomized rats. Rats were ovariectomized at the beginning of the study. On day 7 of the study, 5-mg slow release pellets of tamoxifen or placebo were implanted sc. All of the rats were killed on day 28 of the experiment. Sections of the proximal tibial metaphysis were stained for acid phosphatase and evaluated histomorphometrically. Ovariectomy resulted in marked loss of bone. Compared to the values in sham-operated animals, the trabecular bone at a sampling site in the secondary spongiosa of ovariectomized rats was reduced by more than 60%, the length of trabecular bone surface covered by osteoclasts was increased by 563%, the percentage of trabecular bone surface covered by osteoclasts was increased by 567%, the mean osteoclast size was increased by 84%, and the number of nuclei per osteoclast was increased by 38%. In contrast, treatment of ovariectomized rats for 3 weeks with tamoxifen restored the histomorphometric measurements to values comparable to those in sham-operated animals. 17 beta-Estradiol increased trabecular bone fractional area in ovariectomized and sham-operated rats, and administration of tamoxifen to estrogen-treated, ovariectomized, and sham-operated animals produced a further increase in trabecular bone. In summary, 1) ovariectomy resulted in large increases in both the number and activity of osteoclasts, 2) the increased bone resorption associated with ovariectomy produced a net loss of trabecular bone, and 3) treatment of ovariectomized rats with tamoxifen prevented these skeletal changes. The results indicate that in the rat, tamoxifen mimics the effects of estrogen on trabecular bone at concentrations that are not uterotropic.

The catechol estrogen, 4-hydroxyestrone, has tissue-specific estrogen actions

“…In contrast, 16 -OHE 1 acted as a full estrogen agonist on the bone and liver and a partial estrogen agonist on the uterus and mammary gland. In this regard, this endogenous estrogen resulted in similar effects to those seen with anti-estrogens such as tamoxifen and raloxifene (Evans et al 1994, Ke et al 1995, Evans et al 1996, Turner et al 1988.…”

17β-Estradiol and Tamoxifen Prevent the Over-Glycosylation of Rat Trabecular Bone Collagen Induced by Ovariectomy

“…In order to provide direct evidence on the relationship between collagen glycosylation of trabecular bone and estrogens, the ovariectomized animals were treated with either 17ß-estradiol or with the partial agonist of the estrogen receptor, tamoxifen (5,6). This paper, which is a continuation of the previous one (1), reports the results obtained in this investigation.…”

Antiestrogens: structure-activity relationships and use in breast cancer treatment

“…2011, Martinkovich et al . 2014), has antagonist effects on breast cancer cell proliferation but has an estrogen-like action in bone in patients and in animal models, where it helps maintain bone mineral density in postmenopausal women, and has favorable agonist effects on lipid profiles (Turner et al . 1988, Ward et al .…”