Effect of raloxifene on bone mineral density in premenopausal women at increased risk of breast cancer.

CONTEXT Raloxifene is a promising breast cancer prevention agent in postmenopausal women at increased risk for breast cancer. The effects of raloxifene in premenopausal women are unknown. OBJECTIVE We evaluated the effect of raloxifene in premenopausal women at increased risk for breast cancer on bone mineral density (BMD). DESIGN This was a phase II clinical trial. SETTING This study was conducted at an academic medical center. PARTICIPANTS Thirty-seven premenopausal women at increased risk for breast cancer enrolled in the trial. Thirty subjects began treatment and 27 were evaluable. INTERVENTION Raloxifene (60 mg daily) and elemental calcium (500 mg daily) were given for 2 yr. Subjects were followed up off medications for 1 yr. MAIN OUTCOME MEASURE The primary end point was the intrasubject percent change in BMD at 1 yr measured by dual-energy x-ray absorptiometry. RESULTS The mean baseline lumbar spine density was 1.027 g/cm(2). Lumbar spine density decreased 2.3% at 1 yr (P < 0.00001) and 3.5% at 2 yr (P < .00001). Percent change from yr 2 to 3 was +1.4%. The mean baseline total hip bone density was 0.905 g/cm(2). Total hip density decreased 0.3% at 1 yr and 1.0% at 2 yr (P = 0.033). Percent change from yr 2 to 3 was +1.7%. CONCLUSIONS Raloxifene use is associated with a decrease in BMD in premenopausal women at increased risk for breast cancer. The clinical significance of this decrease is unknown and is attenuated with stopping raloxifene.