This study investigated the timing and effects of zoledronate infusions in long-term denosumab users having reached T-score targets (BMD > -2.0 T-score). Findings support that early and multiple zoledronate injections are needed to preserve as much BMD as possible after stopping denosumab. PURPOSE: This study evaluated the effects of zoledronate (Zol) administration and the need for multiple infusions to prevent bone loss after stopping denosumab (Dmab) in long-term users, and the influence of previous bisphosphonates (BPs) exposure. METHODS: This was a multicentric, randomized, open-label study, including 44 post-menopausal women treated with Dmab > 2 years and reaching BMD T-scores > -2.0. Patients without pre-Dmab BPs were randomized into 3 groups receiving Zol at 6 months (6 M, n = 12) or 9 months (9 M, n = 11) after the last Dmab, or to a group receiving Zol if CTX > 644 ng/l or BMD decreased ≥ 5% (OBS, n = 11). A parallel observational group exposed to pre-Dmab BPs (OBS-BPs, n = 10) received Zol under the same criteria as the OBS group. Zol was re-administered during the 2‑year follow‑up according to CTX threshold or BMD loss criteria. Co-primary outcomes were lumbar spine BMD changes 1-year post-Zol and frequency of Zol treatments required. RESULTS: A majority of post-Dmab patients without previous BPs required multiple Zol infusions (median 2, range 1-5), while most patients in OBS group with previous BPs needed only one Zol. Median LS BMD changes 12 and 24 months post-Zol were similar between groups. However, LS BMD changes at 12 months after the end of the last Dmab dose effect were numerically larger in 9 M group (-8.25%) and OBS group (-8.13%) than in 6 M (-4.71%) and OBS-BPs (-4.62%) groups. CONCLUSION: Findings support that early and multiple Zol injections are needed better to preserve BMD after stopping Dmab in long-term users.
Ferrari et al. (Sun,) studied this question.