Benefits and risks of raloxifene by vertebral fracture status.

Objective: Women without versus those with vertebral fracture may have different benefits and risks during raloxifene treatment. Our objective was to compare the effects of raloxifene to decrease risk for vertebral fracture and invasive breast cancer with its effect to increase risk for venous thromboembolism in postmenopausal women without or with baseline vertebral fracture.
Research Design and Methods: The Multiple Outcomes of Raloxifene Evaluation trial included postmenopausal women with osteoporosis randomized to placebo, raloxifene 60 mg/day, or raloxifene 120 mg/day for 4 years. The protocol specified subgroups based on whether or not patients had a vertebral fracture at baseline. Absolute differences between placebo and raloxifene 60 mg/day (the approved dose) for endpoints in these groups were defined as the incidence in the raloxifene group minus the incidence in the placebo group.
Results: Raloxifene decreased the incidence of vertebral fracture and invasive breast cancer while increasing the incidence of venous thromboembolism. All treatment by vertebral fracture status interaction p-values were greater than 0.13, indicating that the effect of raloxifene on these outcomes was not significantly different between patients without versus those with vertebral fractures. In women without baseline vertebral fracture, absolute risk differences between the raloxifene and placebo group included vertebral fracture -2.83%, invasive breast cancer -1.21%, and venous thromboembolism +0.28%. In women with baseline vertebral fracture, absolute risk differences between raloxifene and placebo group included vertebral fracture -8.21%, invasive breast cancer -0.75% and venous thromboembolism +0.91%. The analysis had limited power to test whether raloxifene had a significantly different effect on venous thromboembolism in women without versus those with a vertebral fracture.
Conclusions: In women without and in those with vertebral fractures at baseline, the effects of raloxifene to decrease vertebral fracture and invasive breast cancer were greater than its effects to increase venous thromboembolism.