552 Background: The management of bone mineral density (BMD) in postmenopausal, breast cancer (BC) patients (pts) receiveing anastrozole was investigated in this phase III, multicenter, open label trial. Methods: Pretreatment BMD of 217 eligible pts with hormone receptor-positive BC scheduled to receive anastrozole was evaluated at lumbar spine (LS) and hip (HP). Pts with T-score<-2.0 in LS or HP, received anastrozole 1mg/day plus oral risedronate 35 mg/week (A+R) and pts with T-score>-1 in both sites received anastrozole only (A). Pts with T-score<-1 in either site but T-score>-2.0 in both sites were randomized to receive A+R or A alone. All pts received Calcium and Vit D daily. BMD was then assessed at 12 and 24 months. Results: Comparison of randomized arms (A = 33 pts, A+R = 37 pts): T-score change from baseline was significantly different only for LS at 24 months (-0.23 in A vs 0.41 in A+R, Wilcoxon test p = 0.007) and was significantly higher from baseline for the A+R arm (Signed rank test p = 0.01). At 12 months, among A only pts, 4 (12.1%) had a T-score<-2.0 without becoming osteoporotic, while 2(6.1%) moved to the normal BMD region; from A+R pts, only 2(5.4%) had a T-score<-2.0 without becoming osteoporotic, while 9 (24.3%) moved to the normal BMD region. The same trend in BMD changes was also observed at the 24 month evaluation. Group with T-score<-2.0 in either LS or HP (A+R, n = 99): a significant increase for LS both at 12 and 24 months was detected (median increase of T-score by 0.45 and 0.37, p<0.01 for both time points) with a corresponding non-significant change in HP (p = 0.91 and p = 0.15). BMD in 13(13.3%) pts improved to the osteopenic region (-2.0<T-score<-1.0). Group with T-score>-1 in both sites (A, n = 48): significant decrease was detected for HP and LS, both at 12 and 24 months; however, only 11 (22%) pts became osteopenic and 1(2%) became osteoporotic. Conclusions: The addition of oral risedronate in postmenopausal BC patients with osteopenia receiving anastrozole has a favourable effect in BMD at lumbar spine at 24 months. [Table: see text]