Background: The NCCN recommends serial bone mineral density (BMD) measurement with dual energy x-ray absorptiometry (DXA) to diagnose and treat AI-associated osteoporosis. The FRAX algorithm identifies additional patients with ORFR who may benefit from anti-resorptive therapy (ART). The TBS, which measures bone microstructure by DXA, is an independent indicator of ORFR. Here, we retrospectively evaluate the utility of a combined screening approach (BMD+FRAX+TBS) in identifying ORFR at baseline and following AI. Methods: Breast cancer patients > 60 years, treated with AI and no ART between 2006-12, who had serial DXA at Memorial Sloan Kettering Cancer Center were identified (n= 74). BMD, FRAX, and TBS were evaluated at baseline (< 3 months from AI initiation) and at 12-24 months, and various screening strategies for identifying ORFR were assessed. Based on National Osteoporosis Foundation criteria and Manitoba TBS study fracture rates, ORFR was defined as: BMD T-score≤-2.5; ≥3% hip or ≥20% osteoporosis-associated 10-year fracture risk by FRAX; or TBS score≤1.2 with BMD T-score< -1.0. Results: Following AI, lumbar spine (LS)-BMD declined in 75% of patients (median: -2.9%; SD: 4.3%) and TBS declined in 58% of patients (median: -1.0%, SD: 7.7%). Declines in LS-BMD and TBS were not correlated (Spearman r=-.16, p=NS) and were not influenced by age, BMI, ethnicity, or chemotherapy (by Wilcoxon rank-sum). Compared to BMD alone, a combined screening approach (BMD+FRAX+TBS) identified an additional 15% of patients with ORFR at baseline. (table) Following AI, an additional 2% developed ORFR by BMD alone, versus 7% by BMD+FRAX+TBS. Conclusions: AIs caused bone loss, leading to ORFR as measured by BMD, FRAX, and TBS. Because FRAX and TBS are derived from DXA and patient history, a combined screening approach may efficiently and cost-effectively identify additional BC patients with ORFR who may benefit from ART.