9630 Background: The bisphosphonate (BP) ZOL is frequently used to prevent skeletal-related events (SRE) in cancer pts. However, data are limited on its use beyond 2 years. LOTUZ is among the first studies to examine Rx and outcomes in pts with ZOL Rx for >2y. We report 6-month results. Methods: Prospective (18m), multicenter (50), pharmacoepidemiologic study. Baseline (0m) and 6m data available on 205 pts (of 298 enrolled), all free from osteonecrosis of the jaw (ONJ) at 0m. Prior to ZOL Rx, 27.8% had non-ZOL BP Rx. Mean pre-enrollment BP duration was 42 mo (23–145) with 38 mo (23–80) for ZOL. Results: Mean age: 64 y (38–88); M/F: 29/71%; 67.8% with MBD vs 32.2% MM. 89.3% continued ZOL RX 0–6m; 90% with dose 4mg. From 0–6m, 10 pts (4.8%) developed ONJ (4 with MM, 6 with MBD): 5 mild, 3 moderate, 2 severe (median BP duration: 38.4, 46.5, and 34.8 months, respectively). Five pts with ONJ continued on ZOL RX 0–6m (3 mild, 2 moderate). 4/10 pts with ONJ had baseline dental conditions or procedures, 8/10 at 6m (only 1/10 at neither). SREs and pain levels remained constant 0–6m compared to 6m prior to baseline (see Table ). Conclusions: Beyond 2y, 90% of pts were continued on ZOL. SREs did not increase, but ONJ was diagnosed in 10/205 pts 0–6m, of which 5 were on ZOL RX beyond 24m. Long-term data are needed to better understand the risk/benefit of long-term ZOL Rx. [Table: see text] [Table: see text]