OR01-5 Transition From Low Dose Denosumab 30mg to IV Zoledronic Acid: Effect on Bone Mineral Density in Postmenopausal Women with Osteoporosis: A Prospective Observational Study

Abstract

Abstract Introduction Cessation of denosumab(Dmab), a fully human monoclonal antibody to RANK-ligand, is associated with rises in bone remodelling, reductions in bone mineral density(BMD) and an increased fracture risk. We previously reported that BMD was stable following a switch from Dmab 60mg to 30mg in postmenopausal women with osteoporosis at a moderate fracture risk(1). The primary objective of this extension study is to evaluate the effect of switching patients from 30mg Dmab(6monthly) to IV Zoledronic acid (ZA), administered 6 months following the last dose of Dmab, in preventing bone loss in postmenopausal women with osteoporosis who are no longer at a high fracture risk. Methods Postmenopausal women with osteoporosis at a moderate or low fracture risk, previously on 30mg of Dmab 6monthly were switched to receive 5mg of IV ZA. Exclusion criteria included an additional skeletal disorder, prior fragility fracture, or use of oral steroids (daily in the past 12months). The primary endpoints were the mean percent change in BMD at the lumbar spine(LS), total hip(TH), femoral neck(FN) and 1/3radius(1/3R), as well as the percent change in alkaline phosphatase(ALP) at 24 months compared to baseline, following transition to IV ZA. Secondary outcomes were clinical fractures. Results 8 patients were included in the study. The mean duration of 30mg Dmab prior switching to IV ZA was 14.6 ± 2.8 months. Mean percent change in BMD at LS was -3.04(CI: 5.77, -0.32, p =0.033) and mean absolute change was -0.025gm/cm2(CI: -0.048, -0.002, p=0.038). The percent change at the TH was -2.64(CI: -4.97, -0.31, p=0.031) with a mean absolute change of -0.021 gm/cm2(CI: -0.040, -0.002, p=0.038). There were no statistically significant changes at the FN, or 1/3R sites at 24months post IV ZA. ALP showed 45.5% increase on average at 24months compared to baseline(95% CI: 14.1, 76.9, p=0.011). No clinical fractures were observed. Conclusions We observed a statistically significant decline in mean percent change in BMD at the LS and TH following a switch from 30mg Dmab to IV ZA at 24months following IV ZA administration. This is similar to the data seen following a switch from standard dose Dmab(60mg 6monthly) to IV ZA(2). The small decline in BMD seen maybe within the precision error of the assessment and this requires further evaluation in a larger number of patients. This was associated with a rise in ALP, however we did not observe any clinical fractures in this study.