Anastrozole has been shown to prevent breast cancer in postmenopausal women at high risk of the disease, but has been associated with substantial accelerated loss of bone mineral density (BMD) and increased fractures. Here, we investigate the effect of risedronate on BMD after 5 years of follow-up in the IBIS-II prevention trial. 1410 women were enrolled in the bone sub-study and stratified into three strata according to the lowest baseline T-score at spine or femoral neck. The objective was to compare the effect of oral risedronate (35 mg weekly) versus placebo in osteopenic women in stratum II who were randomised to anastrozole in the main study. 258 osteopenic, postmenopausal women at high risk of developing breast cancer for whom baseline and follow-up bone mineral density measurements were available. 5-year mean BMD change at the lumbar spine for osteopenic women randomised to anastrozole and risedronate was -0.4% compared to -4.2% for those not on risedronate (P < 0.0001) but not significantly different between risedronate users and non-users at the hip (P = 0.2). 5-year mean PINP change was -20% for those randomised to anastrozole and risedronate compared to 3% for those not on risedronate but on anastrozole (P < 0.0001). Our results confirm the bone loss associated with the use of anastrozole and show that anastrozole-induced BMD loss in the spine can be controlled with risedronate treatment. However, our results suggest that weekly oral risedronate is unable to completely prevent anastrozole induced bone loss at the hip.