Effects of 16 weeks of treatment with tibolone on bone mass and bone mechanical and histomorphometric indices in mature ovariectomized rats with established osteopenia on a low-calcium diet

Tibolone is a synthetic steroid with tissue-specific estrogenic, progestoge nic, and androgenic properties. The therapeutic effects of tibolone on bone mass and strength, bone metabolic markers, and indices of histomorphometry were investigated in ovariectomized (ovx) rats on a low (0.1%)-calcium die t in comparison with 17 alpha-ethynylestradiol (EE) or 1 alpha-hydroxyvitam in D-3 [1 alpha(OH)D-3]. Tibolone (0.1-3 mg/kg/day), EE (0.1 mg/kg/day), or 1 alpha(OH)D-3 (0.5 mu g/kg/day) was administered orally once a day for 16 weeks, starting 12 weeks after ovariectomy, when the hone mineral density (BMD) of lumbar vertebrae (L4-5) and femur (global, proximal, and distal re gions) had already been decreased by the combination of ovariectomy and low dietary calcium. The BMD of the lumbar vertebrae and the femur were higher in the groups treated with tibolone, EE, or 1 alpha(OH)D-3 than in the ovx control group. The BMD of the mid-diaphysial regions of femur and tibia, w hich consist mainly of cortical bone, were decreased 28 weeks after ovariec tomy in the ovx control group. The BMD of the mid-diaphysial femur was high er in the groups treated with 1 alpha(OH)D-3, and the BMD of middiaphysial tibia was higher in the groups treated with tibolone or 1 alpha(OH)D-3 than in the ovx control group. Like BMD, the compressive strength of the verteb ral body of L2, corrected for the volume of each individual vertebra tested , was higher in the groups treated with tibolone, EE, or 1 alpha(OH)D-3 tha n in the ovx control group. Trabecular bone volume and trabecular number we re reduced 12 and 28 weeks after ovariectomy but there was no change in tra becular thickness. These reduced indices were increased in the groups treat ed with tibolone, EE, or 1 alpha(OH)D-3 when compared with the ovx control group. Tibolone or EE decreased serum levels of osteocalcin and bone alkali ne phosphatase and urinary levels of deoxypyridinoline and pyridinoline com pared with the ovx control group. Furthermore, tibolone or EE decreased the mineralizing surface and bone formation rate as well as the osteoclast sur face and osteoclast numbers. 1 alpha(OH)D-3, however, did not affect these serum and urinary parameters. These data suggest that tibolone suppresses t he accelerated bone turnover induced by a combination of ovariectomy and lo w dietary calcium, and indicate that tibolone may be a potentially useful d rug for the treatment of postmenopausal osteoporosis. (C) 1999 by Elsevier Science Inc. All rights reserved.