Tibolone and its effects on bone: a review.

This review examines the evidence for the effects of tibolone on bone. Tibolone is a synthetic steroid with a mixed (estrogenic-progestogenic-androgenic) hormonal profile. Data suggest a complex receptor-mediated as well as metabolic regulation of the activity of tibolone at target tissue level. It has been shown that tibolone can prevent axial and appendicular bone loss induced by ovariectomy and/or a low calcium diet in young and mature rats. In addition, tibolone increases trabecular and cortical bone mineral density in rats with established osteopenia. In the rat, treatment with tibolone results in an increased strength of the femoral neck and of the vertebral body, similar to that found with estrogens. The protective effect on bone can be blocked by antiestrogens, indicating that the effect is estrogen receptor-mediated. Clinical trials have shown that loss of bone in the spine and proximal hip can be prevented with tibolone 2.5 mg/day in early- and late-postmenopausal women. In addition, a dose of 1.25 mg/day seems also to be effective, especially in late-postmenopausal women. In women with established osteoporosis, bone density of the axial and appendicular skeleton increases with tibolone. In comparative studies, tibolone 2.5 mg/day seems to be as effective as conventional hormone replacement therapy regimens. There are no direct comparative studies between tibolone and bisphosphonates or raloxifene. Furthermore, to establish the efficacy of tibolone for prevention of osteoporotic fractures, studies of the magnitude of reduction in fracture risk remain to be conducted. Finally, tibolone seems to be effective in preserving bone density in patients treated with gonadotropin-releasing hormone agonist.