Discontinuation of denosumab is associated with a rapid return of bone mineral density (BMD) to baseline and an increased risk of multiple vertebral fractures. No subsequent treatment regimen has yet been established for preventing either loss of BMD or multiple vertebral fractures after denosumab discontinuation. The aim of this 8‐year observational study was to investigate the effect of a single zoledronate infusion, administered 6 months after the last denosumab injection, on fracture occurrence and loss of BMD. We report on 120 women with postmenopausal osteoporosis who were treated with 60 mg denosumab every 6 months for 2 to 5 years (mean duration 3 years) and then 5 mg zoledronate 6 months after the last denosumab injection. All patients were evaluated clinically, by dual‐energy X‐ray absorptiometry (DXA) and vertebral fracture assessment (VFA), before the first and after the last denosumab injection and at 2.5 years (median) after denosumab discontinuation. During this off‐treatment period, 3 vertebral fractures (1.1 per 100 patient‐years) and 4 nonvertebral fractures (1.5 per 100 patient‐years) occurred. No patients developed multiple vertebral fractures. Sixty‐six percent (confidence interval [CI] 57% to 75%) of BMD gained with denosumab was retained at the lumbar spine and 49% (CI 31% to 67%) at the total hip. There was no significant difference in the decrease of BMD between patients with BMD gains of >9% versus <9% while treated with denosumab. Previous antiresorptive treatment or prevalent fractures had no impact on the decrease of BMD, and all bone loss occurred within the first 18 months after zoledronate infusion. In conclusion, a single infusion of 5 mg zoledronate after a 2‐ to 5‐year denosumab treatment cycle retained more than half of the gained BMD and was not associated with multiple vertebral fractures, as reported in patients who discontinued denosumab without subsequent bisphosphonate treatment. © 2020 American Society for Bone and Mineral Research.

中文翻译：

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Denosumab停药后绝经后妇女单次注射唑来膦酸盐会导致部分保留骨量增加。

地诺单抗的中止与骨矿物质密度（BMD）快速恢复至基线以及多发性脊椎骨折的风险增加相关。denosumab停用后，尚未建立预防BMD丢失或多发性脊椎骨折的后续治疗方案。这项为期8年的观察研究的目的是研究在最后一次denosumab注射后6个月内单次唑来膦酸盐输注对骨折发生和BMD损失的影响。我们报道了120名绝经后骨质疏松症的妇女，每6个月用60 mg地诺单抗治疗2至5年（平均持续时间3年），然后在最后一次denosumab注射后6个月用5 mg唑来膦酸盐治疗。所有患者均经过临床评估，在首次denosumab注射前和末次注射后，以及在denosumab停药后的2.5年（中位），通过双能X线骨密度仪（DXA）和椎骨骨折评估（VFA）进行评估。在这段非治疗期间，发生了3例椎体骨折（每100例患者年1.1例）和4例非椎体骨折（每100例患者年1.5例）。没有患者发生多发性脊椎骨折。用denosumab获得的BMD有66％（置信区间[CI] 57％至75％）保留在腰椎，而49％（CI 31％至67％）保留在整个髋部。地诺单抗治疗时，BMD增高> 9％的患者与<9％的患者之间，BMD的降低没有显着差异。先前的抗吸收治疗或普遍的骨折对BMD的降低没有影响，唑来膦酸盐输注后的前18个月内所有骨质流失均发生。总的来说，如在未接受双膦酸盐治疗的情况下停用denosumab的患者报告的那样，在2至5年的denosumab治疗周期后单次输注5 mg唑来膦酸盐可保留获得的BMD的一半以上，并且与多发性脊椎骨折无关。©2020美国骨骼和矿物质研究学会。