Tibolone and its effects on bone: a review

Abstract

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.

Endocrinology of menopause

“…Based on the evidence available, the panel proposed a number of subgroups of postmenopausal women with vasomotor symptoms in whom tibolone might have added value; these included women with sexual dysfunction, mood disorders, fibroids and urogenital complaints, as well as those with breast tenderness or high mammographic breast density as a result of estrogen use (53). Tibolone appears to preserve bone mass after menopause, and its effect is blocked by anti‐estrogens, supporting the hypothesis that its effect is mediated by estrogen (4). Adverse effects of tibolone include pain, weight gain, and headache.…”

The Role of Hormone Replacement Therapy (HRT) and Tibolone in the Prevention and Treatment of Postmenopausal Osteoporosis

“…Experimental data conclude that tibolone is as effective as estrogen to prevent bone loss secondary to the decline of ovarian function, observed even in osteopenic rats an increase in BMD and femoral and vertebral bone strength, similar to estrogen (Berning et al, 2001). In humans, the action of tibolone on the skeletal system is also largely mediated by estrogen receptor binding and stimulation of it by some of its metabolites.…”

Could female steroids lead to osteonecrosis of the jaw?

“…To the Editor, Tibolone (TB) is a synthetic female steroid with a hormonal profile that was first introduced in the Netherlands in 1988, as the treatment for vasomotor symptoms and to prevent bone fractures in postmenopausal woman with osteopenia. 1 It is well described in the literature the effects of TB on the bone metabolism, even with lower doses and a short period of time.…”

“…The protective effects of TB and 17BE on BMD and bone metabolism have been demonstrated both in animal and human studies. 1,4 In addition, the bone metabolism is modulated, suppressing not only the bone resorption but also the neoformation. 5 TB could even influence more on the bone metabolism and osseointegration process than alendronate or simvastatin 6 TB therapy suppress bone turnover markers such as serum alkaline phosphatase, osteocalcin and urinary hydroxyproline.…”

“…5 TB could even influence more on the bone metabolism and osseointegration process than alendronate or simvastatin 6 TB therapy suppress bone turnover markers such as serum alkaline phosphatase, osteocalcin and urinary hydroxyproline. 1,2 A network meta-analysis concluded that TB has the same potential to affect the bone turnover as other related to osteonecrosis of the jaw (MRONJ) drugs. [3][4][5] This could be explained by the alternate effect of TB on E receptors, that is also present in some bisphosphonates.…”