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Taylor & Francis Journals Auto-Holdings Collection
Beschreibungen/Notizen
The effects of trimegestone (1 mg/kg/day orally) ,a novel norpregnane progestin ,and 17β-estradiol (10 g/kg/day subcutaneously) ,alone and in combination ,on bone mass and turnover were investigated
using an experimental model of osteoporosis involving ovariectomized rats. An equivalent dose (1 mg/kg/day orally) or norethisterone was used as a reference progestin. Six-month-old rats were ovariectomized
and left untreated for 2 months to allow the development of osteopenia. Treatment with a progestin ,alone or in combination with estradiol ,was then started and continued for 2 months. Bone was assessed
by a combination of static and dynamic histomorphometric measurements ,by densitometry and by the use of biochemical markers of bone turnover. Ovariectomy induced a pronounced uterine atrophy ,which was
reversed by estradiol. Trimegestone effectively counteracted the uterotropic effect of estradiol ,whilst norethisterone showed a less pronounced antagonistic effect. A severe osteopenia was established
in the initial 2 months after ovariectomy ,and further bone loss occurred during the 2-month treatment period in animals not receiving estradiol. This effect was associated with a marked increase in both
biochemical and dynamic histomorphometric markers of bone turnover ,reflecting in an imbalance between resorption and formation. 17β-estradiol given alone prevented further bone loss ,but neither trimegestone
nor norethisterone alone had a beneficial effect on bone mass and turnover. When given in combination with 17β-estradiol ,however ,trimegestone significantly improved its effect on bone mass and turnover.
This effect was more potent than that induced by combined 17β-estradiol and norethisterone therapy. We conclude that trimegestone ,when combined with 17β-estradiol ,is a more effective progestin
than norethisterone in preventing bone loss in adult ovariectomized rats.