SAT-778 Bone Mineral Density Changes in Postmenopausal Women Switching from 30 mg Denosumab to Intravenous Zoledronic Acid: A Prospective Observational Study

Abstract Disclosure: D.S. Ali: None. Z. Chung: None. L. Kamel: None. A.A. Khan: Takeda, research funds, research funds from Ascendis, Amolyt. Background: In postmenopausal women with osteoporosis, discontinuation of denosumab (Dmab), has been associated with increased bone turnover, reductions in bone mineral density (BMD), and increased risk of vertebral compression fractures. Our previous observational study demonstrated that transitioning from Dmab 60mg to 30mg maintained stable BMD in this population at moderate fracture risk1. The primary objective of this extended study is to evaluate the effectiveness of transitioning from 30mg Dmab q6 months to IV zoledronic acid (ZA), administered 6 months after the last Dmab dose, in preventing bone loss in postmenopausal women with osteoporosis who are no longer at high fracture risk. Methods: Women with postmenopausal osteoporosis at low to moderate fracture risk, previously treated with 30mg Dmab every 6 months, were switched to 5mg IVZA. The study excluded individuals with additional skeletal disorders, prior fragility fractures, or recent daily use of oral steroids. Primary endpoints included assessing changes in BMD at the lumbar spine(LS), total hip(TH), femoral neck(FN), 1/3 radius(1/3R), and alkaline phosphatase activity (ALP) at 24 months post-transition to IVZA. Secondary outcome was the incidence of clinical fractures during the study period. Results: Twenty women were included. The mean duration of 30mg Dmab prior to IVZA was 29.6±18.0 months. Mean percent change in BMD at LS was -3.7%(95%CI: -6.99, -0.43) and mean absolute difference was -0.034 gm/cm2(95%CI -0.067, 0.000, p=0.001). Mean percent change at TH was -2.2%(95%CI: -4.07, -0.24), with a mean absolute difference of -0.012(95%CI -0.023, -0.001, P=0.002). The FN and 1/3R showed no significant changes. ALP increased by 46% (p<0.001) at 24 months compared to baseline. No clinical fractures were observed. Predictors for BMD changes, including prior Dmab duration and fracture risk, showed no significant associations. Conclusions: At 24 months following the switch from 30mg Dmab to IVZA, we observed significant declines in BMD at the LS and TH (p<0.001). Relative to initial 60mg Dmab use, BMD was preserved at the LS and FN (1.6%) but declined at the 1/3R (-2.6%, p=0.011). No clinical fractures were reported. The decrease in BMD appears to be less than seen with a switch from Dmab 60mg to IVZA in one study (LS:-3.7% vs-4.0%, TH:-2.2% vs-3.5%, and FN:-1.7% vs-3.9%)2. This observation requires further study. The small decrease in BMD observed in our study may be within the precision error of the assessment and warrants further evaluation in a larger cohort of patients. References: 1.Khan A, etal. Efficacy of Low Dose Denosumab in Maintaining BMD in Postmenopausal Women With Osteoporosis Switching From 60mg to 30mg 6Monthly:A Real World, Prospective Observational Study.JES.2021 2.Sølling, A.S.et al.(2021), Treatment With Zoledronate Subsequent to Denosumab in Osteoporosis:A 2-Year Randomized Study. JBMR. Presentation: Saturday, July 12, 2025