Effect of trimegestone alone or in combination with estradiol on bone mass and bone turnover in an adult rat model of osteopenia

Abstract

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.

• TRIMEGESTONE
• ESTRADIOL
• NORETHISTERONE
• BONE TURNOVER
• OSTEOPENIA
• OSTEOPOROSIS