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, progestogenic, 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 diet in comparison with 17 alpha-ethynylestradiol (EE) or 1 alpha-hydroxyvitamin 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 regions) 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, which consist mainly of cortical bone, were decreased 28 weeks after ovariectomy in the ovx control group. The BMD of the mid-diaphysial femur was higher 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 vertebral 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 than in the ovx control group. Trabecular bone volume and trabecular number were reduced 12 and 28 weeks after ovariectomy but there was no change in trabecular thickness. These reduced indices were increased in the groups treated 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 alkaline phosphatase and urinary levels of deoxypyridinoline and pyridinoline compared with the ovx control group. Furthermore, tibolone or EE decreased the mineralizing surface and bone formation rate as well as the osteoclast surface and osteoclast numbers. 1 alpha(OH)D-3, however, did not affect these serum and urinary parameters. These data suggest that tibolone suppresses the accelerated bone turnover induced by a combination of ovariectomy and low dietary calcium, and indicate that tibolone may be a potentially useful drug for the treatment of postmenopausal osteoporosis. (C) 1999 by Elsevier Science Inc. All rights reserved.