17β Estradiol stimulation of endosteal bone formation in the ovariectomized mouse: An animal model for the evaluation of bone-targeted estrogens

M. W. Edwards, S. D. Bain, M. C. Bailey, M. M. Lantry, G. A. Howard

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

To evaluate the potential of an animal model as a means to identify bone-targeted estrogens, we have studied the response of the skeleton of ovariectomized mice to prolonged estrogen treatment. Seventy female Swiss-Webster mice were randomly divided into ten groups, with nine groups undergoing bilateral ovariectomy and one group a sham procedure. Mice were injected subcutaneously once per week for nine weeks with one of the following doses of estrogen (17β-E2) in oil vehicle: 19.3, 38.5, 75, 150, 300, 500, 1000, or 3000 μg. One group of ovariectomized (OVX) mice and the sham operated animals received vehicle injections only. At the end of the nine-week experimental protocol, there were no significant differences in body weights among any treatment groups. However, when compared to control values, spleen weights in vehicle-treated OVX mice and in mice treated with 1000 μg or 3000 μg of 17β-E2 were significantly elevated (p < .01). Liver weights in the OVX mice treated with 1000 or 3000 μg 17β-E2 were also increased significantly (p < .05). Comparisons of uterine weights and cortical bone areas were strongly correlated with 17β-E2 dose (r2 = .86 and .94, respectively), with maximal increases observed at estradiol doses in excess of 500 μg per week. Furthermore, based on bone histomorphometry of in vivo fluorochrome labels, increases in cortical bone area could be attributed to accelerated rates of endosteal mineral apposition and bone formation. These results indicate that the comparison of the response of endosteal bone and uterine tissue in the OVX mice to chronic estrogen treatment offers the potential to identify estrogen and/or estrogen-like compounds with bone-specific activity.

Original languageEnglish (US)
Pages (from-to)29-34
Number of pages6
JournalBone
Volume13
Issue number1
DOIs
StatePublished - 1992

Keywords

  • Bone histomorphometry
  • Bone-targeting
  • Endosteal bone formation
  • Estrogen
  • Uterotrophic response

ASJC Scopus subject areas

  • Physiology
  • Hematology

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