High-dose estrogen inhibits bone resorption and stimulates bone formation in the ovariectomized mouse.
In this study, we have investigated estrogen's capacity to regulate bone formation and resorption in the ovariectomized mouse, evaluating the dose and site dependence of estrogen action on bone modeling and remodeling surfaces. To quantitate bone resorption, the skeletons of fifty 8-week-old Swiss-Webster mice were prelabeled with [3H]tetracycline (3H-T) before initiation of treatment protocols. Ovariectomies (OVX) and sham surgeries were performed 3 days after the final 3H-T injection, and the animals were assigned to treatment groups and injected once per week for 4 weeks with one of the following doses of 17 beta-estradiol (E2): sham/oil vehicle (SV), OVX/oil vehicle, OVX/50 micrograms E2, OVX/250 micrograms E2, and OVX/500 micrograms E2. To assess bone formation, fluorochrome labels were administered 9 and 2 days before sacrifice. At the conclusion of the 4 week protocol, the femora and thoracic vertebrae were removed to quantitate the levels of bone resorption based on the skeletal retention of 3H-T. The tibiae were excised for histomorphometric evaluation of the proximal metaphyses and middiaphyses. Indicative of increased bone resorption, vehicle-treated OVX animals had significantly reduced levels of 3H-T in femora and vertebrae compared to SV mice. This result was consistent with histomorphometric data showing a 49% decrease in cancellous bone area of the proximal tibiae in the OVX/oil-treated group. Treatment of OVX animals with 50 micrograms E2 was sufficient to maintain 3H-T levels in vertebrae at SV values, with higher E2 doeses leading to a dose-dependent increase in the retention of 3H-T at this site.(ABSTRACT TRUNCATED AT 250 WORDS)
Bain
S D
SD
Department of Pharmacology and Medical Affairs, ZymoGenetics, Inc., Seattle, Washington.
Bailey
M C
MC
Celino
D L
DL
Lantry
M M
MM
Edwards
M W
MW
D000704:Analysis of Variance; D000818:Animals; D001846:Bone Development / Q000187:drug effects*; D001862:Bone Resorption / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D005260:Female; D051379:Mice; D008856:Microscopy, Fluorescence; D010052:Ovariectomy; D013977:Tibia / Q000187:drug effects / Q000473:pathology
D004958:Estradiol