Discontinuation of denosumab treatment is associated with rapid bone loss that could be prevented in many patients by zoledronate (ZOL) infusion given 6 months after the last denosumab injection. The effects, however, of zoledronate administration at a later time point are unknown. We aimed to compare the 1-year effect of ZOL infusion given 6 versus 18 months following the last Dmab injection. In this extension of a previously reported 2-year randomized clinical trial, we included initially treatment-naive postmenopausal women, who became osteopenic after approximately 2.5 years of denosumab therapy, and were subjected to a single ZOL infusion at 6 months (early-ZOL, n = 27) versus 18 months (late-ZOL, n = 15) after the last Dmab injection. Annual changes in lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD), and markers of bone turnover (P1NP, CTx) at 6 and 12 months following ZOL infusion were assessed. LS BMD was maintained in both early-ZOL (+ 1.7%) and late-ZOL (+ 1.8%) infusion with no difference between groups (p = 0.949). FN BMD was maintained in early-ZOL (+ 0.1%) and increased in late-ZOL (+ 3.4%) infusion with no difference between groups (p = 0.182). Compared to 6 months after last Dmab injection, the overall LS BMD change of the late-ZOL group (− 3.5%) was significantly different (p = 0.007) from that of the early-ZOL group (+ 1.7%). P1NP and CTx gradually increased in the early-ZOL group, while profoundly decreased and remained suppressed in the late-ZOL infusion. A ZOL infusion 18 months following the last Dmab injection is still useful in terms of BMD maintenance and BTM suppression. However, there is no clear clinical benefit compared to the early infusion, while any theoretical advantage is counterbalanced from the expected bone loss, especially at the LS, and the risk of rebound-associated fractures.

Trial Registration: NCT02499237; July 16, 2015

停止狄诺塞麦治疗与快速骨质流失有关，许多患者在最后一次狄诺塞麦注射后 6 个月输注唑来膦酸盐 (ZOL) 可以预防这种情况。然而，唑来膦酸盐在以后的时间点给药的效果是未知的。我们旨在比较最后一次 Dmab 注射后 6 个月和 18 个月输注 ZOL 的 1 年效果。在之前报道的一项为期 2 年的随机临床试验的扩展中，我们纳入了最初未接受治疗的绝经后妇女，她们在大约 2.5 年的狄诺塞麦治疗后出现骨质减少，并在 6 个月时接受了单次 ZOL 输注（早期 ZOL，n = 27）与 18 个月（ZOL 晚期，n= 15) 在最后一次 Dmab 注射后。评估了 ZOL 输注后 6 个月和 12 个月腰椎 (LS) 和股骨颈 (FN) 骨矿物质密度 (BMD) 和骨转换标志物 (P1NP, CTx) 的年度变化。LS BMD 在早期 ZOL (+ 1.7%) 和晚期 ZOL (+ 1.8%) 输注中均保持不变，组间无差异 ( p = 0.949)。FN BMD 在早期 ZOL 中维持（+ 0.1%），在晚期 ZOL 输注中增加（+ 3.4%），组间无差异（p = 0.182）。与最后一次 Dmab 注射后 6 个月相比，晚期 ZOL 组的整体 LS BMD 变化（- 3.5%）有显着差异（p= 0.007) 较早期 ZOL 组 (+ 1.7%)。P1NP 和 CTx 在早期 ZOL 组中逐渐增加，而在晚期 ZOL 输注中显着下降并保持抑制。在最后一次 Dmab 注射后 18 个月输注 ZOL 在 BMD 维持和 BTM 抑制方面仍然有用。然而，与早期输注相比，没有明显的临床益处，而任何理论上的优势都抵消了预期的骨质流失，尤其是在 LS 处，以及反弹相关骨折的风险。

试用注册：NCT02499237；2015 年 7 月 16 日