Tibolone preserves bone mass, prevents bone loss, and is approved in 45 countries for prevention of osteoporosis. Metabolites have estrogenic, progestogenic, and androgenic effects. The effects of tibolone on fractures, breast cancer, and cardiovascular disease are uncertain. This randomized, double-blind, placebo-controlled trial evaluated the effects of 1.25 mg of tibolone daily on the risk of vertebral fracture after 3 years and examines risks of nonvertebral fracture, breast cancer, and cardiovascular disease after 5 years.
The participants were 4538 women between the ages of 60 and 85 years with a bone mineral density T score of -2.5 or less at the hip or spine or a T score of −2.0 or less and radiologic evidence of a vertebral fracture. Vertebral fracture was assessed by annual spine radiographs. Expert panels adjudicated rates of cardiovascular events and breast cancer.
Compared with the placebo group, during a median of 34 months of treatment, tibolone was associated with a decrease in the absolute risk of vertebral fracture of 8.6 (95% confidence interval [CI], 4.4 to 12.9; P < .001) per 1000 person-years and a reduction in the relative hazard of 45% (95% CI, 26 to 59). There was also a reduction in the absolute risk of nonvertebral fracture of 6.9 (95% CI, 1.6 to 12.2; P ≤.01) per 1000 person-years and a 26% reduction in the relative hazard (95% CI, 7 to 42). The risk of vertebral and nonvertebral fractures was higher among women who had already had a vertebral fracture at baseline. Tibolone also decreased the risk of invasive breast cancer (P ≤ .0.02) and colon cancer (P ≤ .0.04). However, because women in the tibolone group had an increased risk of stroke (P ≤ .0.02), the study was stopped prematurely in February 2006. All formal efficacy criteria had been met at that time. No significant risk of coronary events, venous thromboembolism, or endometrial cancer was found in the tibolone group.
These findings indicate that tibolone decreases the risk of vertebral and nonvertebral fractures, breast cancer, and colon cancer in older women with osteoporosis. Because of the increased the risk of stroke, this drug should not be used in elderly women and women with risk factors for stroke.