toremifene and pyridinoline

Tamoxifen and toremifene are two mostly used antiestrogens in the treatment of breast cancer. To compare their effect on bone in postmenopausal breast cancer patients we measured the urinary output of two bone resorption markers, pyridinoline (Pyr) and deoxypyridinoline (Dpyr) as well as bone density (BMD) in 30 breast cancer patients using either tamoxifen (20 mg/day, n = 15) or toremifene (40 mg/day, n = 15) as adjuvant treatment of stage II breast cancer for 1 year. The urinary output of Pyr and Dpyr were assessed before and after 6 and 12 months of the antiestrogen regimen. Lumbar and femoral BMD were measured by dual energy X-ray absorptiometry (DXA) before and after 12 months of treatment. Both tamoxifen and toremifene were associated with significant decreases in Pyr (mean fall 19.6% and 12.6%, respectively) and Dpyr (mean fall 21.6% and 15.5%, respectively) at 6 months. After 12 months' treatment, Pyr decreased by 30.8% and Dpyr by 21.2% in women using tamoxifen and significantly less in women using toremifene (10.1% and 4.9%, respectively). BMD in the lumbar spine decreased by 1.8% in the toremifene group but increased by 0.4% in the tamoxifen group; in the proximal femur, BMD increased slightly during both tamoxifen and toremifene treatment in all sites measured. Individual changes in Pyr and Dpyr at 6 months showed no significant relation to the change in BMD at 12 months. We conclude that tamoxifen (20 mg/day) and toremifene (40 mg/day) reduce the bone resorption similarly, and this can be detected by falls in urinary output of Pyr and Dpyr at 6 months of treatment.

Topics: Amino Acids; Biomarkers; Bone Density; Breast Neoplasms; Cohort Studies; Estrogen Antagonists; Female; Humans; Middle Aged; Postmenopause; Tamoxifen; Time Factors; Toremifene

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. 17beta-oestradiol (5 microg/kg/day, subcutaneously) was used as positive control. One group was also treated with a combination of 17beta-oestradiol (5 microg/kg) and toremifene (3.0 mg/kg). 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 17beta-oestradiol was more efficient. Toremifene did not reverse the ovariectomy-induced reduction of urinary calcium but inhibited the 17beta-oestradiol-related increase. When administered together with oestradiol, toremifene did not reverse the positive effect of 17beta-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.

Topics: Amino Acids; Animals; Biomarkers; Bone and Bones; Bone Resorption; Calcium; Drug Interactions; Estradiol; Estrogen Antagonists; Female; Hydroxyproline; In Vitro Techniques; Ovariectomy; Random Allocation; Rats; Rats, Sprague-Dawley; Toremifene; Uterus