Summary: Changes in bone mineral density (BMD) and trabecular bone score (TBS) were assessed in 70 patients who received either zoledronate (ZOL) ( n = 34) or placebo ( n = 36) for 2 years. In premenopausal women with breast cancer treatment-induced bone loss, 24 months of intravenous ZOL treatment significantly increased the lumbar spine BMD and the TBS. Introduction: The aim of this study was to compare the effects of 4 mg intravenous zoledronate (ZOL) versus placebo (PLB), every 3 months, on the lumbar spine (LS) bone mineral density (BMD) and the trabecular bone score (TBS) in premenopausal women with breast cancer (BC) treatment-induced bone loss. The TBS is a gray-level texture measurement which is related to the bone microarchitecture and considered to be independent of the BMD. Methods: Changes in BMD and TBS were assessed in 70 patients who were recruited in the double-blind, placebo-controlled ProBONE-II trial and randomized to receive either ZOL ( n = 34) or PLB ( n = 36) for 2 years. The changes were assessed at baseline and at 12 and 24 months after treatment initiation. Results: Patients receiving ZOL showed a mean increase in LS BMD from the baseline to 12 (2.17 %) and 24 months (3.14 %) of treatment and a mean increase in the TBS of 2.41 and 0.75 %, respectively. Conversely, patients receiving PLB showed a mean decrease in the LS BMD from the baseline to 12 (−5.02 %) and 24 (−6.43 %) months and a mean decrease of −0.52 and −2.16 % in the TBS, respectively. Changes in the BMD and the TBS from the baseline to 12 and 24 months were all significantly different for ZOL compared to PLB ( p < 0.005). Furthermore, BMD and TBS showed a moderate correlation ranging from 0.28 ( p = 0.087) to 0.47 ( p = 0.003). Conclusions: In premenopausal women with BC, 24 months of intravenous ZOL treatment significantly increased the LS BMD as well as the TBS. [ABSTRACT FROM AUTHOR]