OR10-04 Evaluation of the Efficacy of ZOledronic Acid Administered Once or Twice After Different Durations of DenosuMab Treatment in Postmenopausal Women with Osteoporosis (ZOOM): A Prospective, Single-Center, Open-Label, Parallel, Phase IV Study

Abstract Disclosure: J. Park: None. S. Cho: None. N. Hong: None. Y. Rhee: None. Objectives: This study evaluates the efficacy of zoledronic acid in preventing bone loss in postmenopausal women with osteoporosis who transitioned off denosumab after achieving osteopenia. Methods: In this single-center, open-label, parallel, phase IV clinical trial, 110 postmenopausal women were stratified by prior denosumab duration: less than 2.5 years (Y) (Denosumab < 2.5Y, n = 61) and greater than or equal to 2.5 years (Denosumab ≥ 2.5Y, n = 49). The Denosumab < 2.5Y group received a single dose of zoledronic acid at baseline [ZOL1 group], while the Denosumab ≥ 2.5Y group received one dose at baseline and another at 6 months [ZOL 2 group]. The primary outcome was the percentage change in BMD at the lumbar spine (LS), femoral neck (FN), and total hip (TH) at 12 months, analyzed using a linear mixed model (LMM). The least significant change (LSC) thresholds were defined as 3.03 % (LS), 5.86 % (FN), and 5.04 % (TH). Secondary outcomes included changes in bone turnover markers (C-telopeptide of collagen Type 1 [CTX] and N-terminal propeptide of type I collagen [P1NP]). Results: Baseline demographics, including age, body mass index, and BMD, were similar between groups. The mean number of prior denosumab doses was 2.7 in the ZOL1 group versus 7.1 in the ZOL2 group (p < 0.001). At 12 months, LS BMD decreased by (mean ± SD) -1.1% ± 5.0% in the ZOL2 group, while it increased by 0.7% ± 4.4% in the ZOL1 group (p = 0.047). However, both changes were below the LSC threshold. FN and TH BMD percentage changes did not differ significantly between the two groups. At 6 months, the ZOL2 group showed a marked elevation in both CTX and P1NP levels compared to baseline (p < 0.001) and the ZOL1 group (p < 0.001). However, by 12 months, CTX and P1NP levels decreased and stabilized, with no significant difference between the two groups (p = 0.203 for CTX and p = 0.127 for P1NP, respectively), while remaining elevated in the ZOL1 group. Conclusions: Two doses of zoledronic acid, administered 6 months apart, were less sufficient to maintain LS BMD in long-term denosumab users, but effectively preserved FN BMD and TH BMD. These findings suggest that zoledronic acid acts as an effective sequential therapy for maintaining FN and TH BMD following denosumab cessation. These results support the importance of individualized treatment strategies based on prior denosumab use to optimize post-therapy outcomes. Presentation: Saturday, July 12, 2025