EFFECT OF TIBOLONE ON POSTMENOPAUSAL BONE LOSS

A 2-year non-randomized prospective study was carried out in a teaching hospital menopause clinic to assess the effect on the skeleton of tibolone (Livial, Organon) 2.5 mg daily in recently postmenopausal women. One hundred women who were between 6 and 36 months since their last menstrual period and had raised gonadotrophin levels consistent with the menopause were allocated into two groups. One group received 2.5 mg tibolone daily and the other group no medication. Bone densitometry of the spine and femur was performed at 0, 6, 12 and 24 months and biochemical markers of bone metabolism were assessed at these points. Severity of hypo-oestrogenic symptoms was assessed at baseline and at 1 and 2 years. After 2 years there was a significant increase in bone mass as measured by dual energy X-ray absorptiometry (DXA) of 2.5% in the spine, and 3.5% in the neck of femur in the women who took tibolone (n = 46), whereas in the control group (n = 45) bone loss occurred (spine, 2.9% femur, 3.7%). When these changes were compared they were significantly different for both sites (p < 0.001). In the treatment group the urinary hydroxyproline/creatinine and calcium/creatinine ratios fell from 0.014 (0.002-0.027) to 0.010 (0.000-0.111) (mol/l) (mmol/l) (p <0.01) and 0.47 (0.08-0.96) to 0.33 (0.09-1.20) (mmol/l) (mmol/l) (p <0.001) respectively, while the serum osteocalcin and alkaline phosphatase decreased from 1.90 (0.20-4.70) to 1.00 (0.00-3.00) mmol/l (p <0.01) and 190 (92-301) to 138 (91-283) mmol/l (p <0.001) respectively. In conclusion we have found that tibolone given in the early postmenopausal years suppresses skeletal metabolism and prevents bone loss in both spine and femur. Tibolone therefore has a potentially important long-term role in the reduction of the incidence of osteoporotic fractures, particularly in view of the compliance that 'bleed-free' therapy will encourage.