Comparative Effect of Zoledronate at 6 Versus 18 Months Following Denosumab Discontinuation
Comparative Effect of Zoledronate at 6 Versus 18 Months Following Denosumab Discontinuation
复制标题
DOI：
10.1007/s00223-020-00785-1
复制
发表时间：
2021-01-02
影响因子：
4.2
通讯作者：
Makras, Polyzois
中科院分区：
文献类型：
--
作者：
Anastasilakis, Athanasios D.;Polyzos, Stergios A.;Makras, Polyzois
地舒单抗治疗停药与快速骨丢失相关，在许多患者中，可通过在末次地舒单抗注射后6个月输注唑来膦酸盐（ZOL）来预防。然而，唑来膦酸盐给药后的效应尚不清楚。我们旨在比较末次Dmab注射后6个月与18个月给予ZOL输注的1年效应。在先前报告的2年随机临床试验的扩展中，我们纳入了最初未经治疗的绝经后女性，这些女性在地舒单抗治疗约2.5年后出现骨质减少，并在末次Dmab注射后6个月（早期ZOL，n = 27）与18个月（晚期ZOL，n = 15）接受单次ZOL输注。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）以及骨转换标志物（P1NP、CTx）的年度变化。LS BMD在早期ZOL（+1.7%）和晚期ZOL（+1.8%）输注中均得以维持，组间无差异（p = 0.949）。FN BMD在早期ZOL（+0.1%）中保持不变，在晚期ZOL（+3.4%）输注中增加，组间无差异（p = 0.182）。与末次Dmab注射后6个月相比，晚期ZOL组的总体LS BMD变化（-3.5%）与早期ZOL组（+1.7%）显著不同（p = 0.007）。P1NP和CTx在早期ZOL组中逐渐增加，而在晚期ZOL输注中显著降低并保持抑制。末次Dmab注射后18个月的ZOL输注在BMD维持和BTM抑制方面仍然有用。然而，与早期输注相比，没有明确的临床获益，而任何理论优势都被预期的骨丢失（尤其是LS）和反弹相关骨折的风险抵消。试验注册：NCT 02499237; 2015年7月16日
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