Tibolone, a steroid with a tissue-specific hormonal profile, completely prevents ovariectomy-induced bone loss in sexually mature rats

Tibolone (Org OD 14) is a synthetic steroid with combined estrogenic, proge stagenic, and androgenic properties and behaves as a tissue-specific steroi d. In the current study, we determined the effects of a 4-week treatment wi th different doses of tibolone on estrogen deficiency-induced bone loss in mature 3-month-old rats. As a reference, 17 alpha-ethinyl estradiol (EE2) w as used. The frequency of administration, once or twice a day, was also stu died. Bone parameters were determined in sham operated controls, ovariectom ized (OVX) controls and OVX-treated rats. Bone loss was assessed by periphe ral quantitative computed tomography directly and by quantitative Roentgen densitometry after defatting to exclude influence of fat changes. Femoral b one geometric parameters, plasma osteocalcin level, and urinary deoxypyridi noline/creatinine ratio were also determined. Ovariectomy caused a signific ant decrease in trabecular bone mineral density in the distal metaphyseal p art of the femur using both methods, whereas no change in cortical bone den sity was found. Trabecular bone loss was prevented in a dose-dependent mann er by tibolone (250, 1000, and 4000 mu g/rat/day) when given once or twice daily. EE, also prevented trabecular bone loss but its efficacy was depende nt upon the frequency of dosing. Both tibolone and EE, induced a significan t reduction in the urinary deoxypyridinoline/creatinine ratio and plasma os teocalcin level. Tibolone and EE2 had no effect on other femoral bone param eters except a reduction in femoral length. In conclusion, treatment with t ibolone for 4 weeks prevented OVX-induced bone loss by suppressing both bon e resorption and bone turnover in a similar way as EE2. However, the freque ncy of dosing is more important for EE2 than for tibolone. Tibolone acts in this animal model for postmenopausal bone loss as an estrogen agonist on b one.