Tsourdi Elena, Zillikens M Carola, Meier Christian, Body Jean-Jacques, Gonzalez Rodriguez Elena, Anastasilakis Athanasios D, Abrahamsen Bo, McCloskey Eugene, Hofbauer Lorenz C, Guañabens Nuria, Obermayer-Pietsch Barbara, Ralston Stuart H, Eastell Richard, Pepe Jessica, Palermo Andrea, Langdahl Bente
Department of Medicine III, Technische Universität Dresden Medical Center, Dresden, Germany.
Center for Healthy Aging, Technische Universität Dresden Medical Center, Dresden, Germany.
J Clin Endocrinol Metab. 2020 Oct 26. doi: 10.1210/clinem/dgaa756.
Denosumab discontinuation is characterized by an increase in bone turnover overriding pre-treatment status, a rapid bone loss in the majority and multiple vertebral fractures (VFx) in some patients.
A working group of the European Calcified Tissue Society (ECTS) performed an updated systematic review of existing literature on changes of bone turnover, bone mineral density (BMD), and fracture risk after denosumab discontinuation and provided advice on management based on expert opinion.
Important risk factors for multiple VFx following denosumab cessation are prevalent VFx, longer duration off therapy, greater gain in hip BMD during therapy, and greater loss of hip BMD after therapy according to a retrospective analysis of the FREEDOM Extension Study. Case series indicate that prior bisphosphonate therapy mitigates the biochemical rebound phenomenon after denosumab discontinuation, but it is uncertain whether this attenuation prevents BMD loss and fractures. Current evidence indicates partial efficacy of subsequent antiresorptive treatment with results seemingly dependent on duration of denosumab treatment.
A careful assessment of indications to start denosumab treatment is advised, especially for younger patients. A case for long-term treatment with denosumab can be made for patients at high fracture risk already on denosumab treatment given the favorable efficacy and safety profile. In case of denosumab discontinuation, alternative antiresorptive treatment should be initiated 6 months after the final denosumab injection. Assessment of bone turnover markers may help define the optimal regimen, pending results of ongoing RCTs. Patients having sustained VFx should be offered prompt treatment to reduce high bone turnover.
地诺单抗停药的特点是骨转换增加，超过治疗前水平，大多数患者骨量快速流失，部分患者发生多发性椎体骨折（VFx）。
欧洲钙化组织协会（ECTS）的一个工作组对关于地诺单抗停药后骨转换、骨密度（BMD）和骨折风险变化的现有文献进行了更新的系统综述，并根据专家意见提供了管理建议。
根据FREEDOM扩展研究的回顾性分析，地诺单抗停药后发生多发性VFx的重要风险因素包括既往存在VFx、停药时间较长、治疗期间髋部BMD增加幅度较大以及治疗后髋部BMD丢失幅度较大。病例系列表明，既往使用双膦酸盐治疗可减轻地诺单抗停药后的生化反弹现象，但这种减轻是否能预防BMD丢失和骨折尚不确定。目前的证据表明，后续抗吸收治疗部分有效，结果似乎取决于地诺单抗治疗的持续时间。
建议仔细评估开始地诺单抗治疗的适应症，尤其是对于年轻患者。鉴于其良好的疗效和安全性，对于已经接受地诺单抗治疗且骨折风险较高的患者，可以考虑长期使用地诺单抗治疗。如果停用 地诺单抗，应在最后一次注射地诺单抗后6个月开始替代抗吸收治疗。在正在进行的随机对照试验结果出来之前，评估骨转换标志物可能有助于确定最佳治疗方案。发生持续性VFx的患者应及时接受治疗，以降低高骨转换状态。
