The Effect of Toremifene on Bone and Uterine Histology and on Bone Resorption in Ovariectomised Rats

Abstract

The effect of the selective oestrogen receptor modulator, toremifene, to inhibit ovariectomy-induced bone loss was studied in rats. The oral doses were 0.3, 3.0 or 30 mg/kg/day for 2 months. 17P-oestradiol ( 5 pgikgiday, subcutaneously) was used as positive control. One group was also treated with a combination of 17P-oestradiol (5 pgikg) and toremifene (3.0 mgikg). Biochemical markers were urinary hydroxyproline and calcium (adjusted with urinary creatinine levels) and the serum level of pyridinoline cross-linked carboxy terminal telopeptide, a bone specific collagen breakdown product. The femoral and sternal trabecular bone thickness served as histological parameters. Ovarectomy increased the levels of hydroxyproline and pyrodinoline and decreased the trabecular bone thickness compared to the sham-operated control group. This was inhibited by both test compounds but 17P-oestradiol was more efficient. Toremifene did not reverse the ovariectomy-induced reduction of urinary calcium but inhibited the 17P-oestradiol-related increase. When administered together with oestradiol, toremifene did not reverse the positive effect of 17P-oestradiol on bone, however toremifene reversed the oestradiol-related uterothrophic effects. These findings indicate that the antagonistic features of toremifene dominate in the rat uterus the agonistic properties do in the bone.

Comparing the effects of atamestane, toremifene and tamoxifen alone and in combination, on bone, serum lipids and uterus in ovariectomized rats

“…As monotherapy TOR has a significant and equivalent stimulatory effect on uterine epithelium as TAM. These monotherapy findings are consistent with published studies in this rat model [24][25][26][27][28][29][30].…”

The effects of atamestane and toremifene alone and in combination compared with letrozole on bone, serum lipids and the uterus in an ovariectomized rat model

“…Our results confirmed that TOR has positive and beneficial effects on bone and lipid metabolism in as far as TOR significantly increased BMD, as well as significantly reduced the rise in serum cholesterol, LDL and TG induced by OVX. However, TOR had a significant stimulatory effect on uterine epithelium [26][27][28][29][30][31].…”