Tibolone (Org OD14), (7alpha, 17alpha)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn++ +-3-one, is a synthetic steroid with weak estrogenic, progestational, and androgenic properties. We investigated the prophylactic effects of tibolone on bone loss, bone strength, and plasma and urinary parameters in 8-month-old ovariectomized rats on a low-Ca diet. Oral administration of tibolone (0.03-3 mg/kg/day) was started immediately after ovariectomy (ovx) and continued for 3 months. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Oral administration of tibolone (1 or 3 mg/kg/day) significantly prevented a decrease in BMD and bone ash density (bone ash weight/volume) of the global femur, and BMDs in the femoral distal and proximal regions. Also in the lumbar vertebrae, the ovx-induced reduction in BMD was prevented by tibolone (1 and 3 mg/kg/ day) treatment, resulting in a significantly higher lumbar vertebral (L-2) bone compression strength compared to the ovx control group. Neither ovx alone nor supplemented with tibolone affected the BMD or bending strength of the femoral mid-diaphysial region. Tibolone (0.03-3 mg/kg/day) significantly reduced the ovx-induced increases in serum osteocalcin level. Furthermore, tibolone inhibited an increase in the urinary hydroxyproline/creatinine, pyridinoline/creatinine, and deoxypyridinoline/creatinine ratios induced by ovx. Tibolone also reduced body weight gain and serum cholesterol level, as has been reported for estrogen. These findings indicate that tibolone prevents reduction in bone mass associated with osteopenia by reducing increased trabecular bone resorption induced by a combination of ovx and a low-Ca diet.