临床停用Denosumab:反弹骨转换的意义和预防骨质流失和骨折的新策略。

IF 5.9 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Shejil Kumar, Mawson Wang, Albert S Kim, Jacqueline R Center, Michelle M McDonald, Christian M Girgis
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引用次数: 0

摘要

Denosumab是一种非常有效的骨质疏松症治疗药物,其长期使用与骨密度(BMD)的增量增加和持续骨折风险降低相关。然而,停用denosumab会导致骨转换的反弹增加,失去治疗相关的骨密度增加,在最坏的情况下,会导致自发性椎体骨折(VFs)。对反弹相关骨质流失的危险因素和潜在机制以及反弹性VFs的真实发生率的见解正在出现。使用双膦酸盐缓解denosumab后反弹的传统策略显示混合性成功。双膦酸盐可以维持短期地诺单抗后的骨密度,但长期地诺单抗后的最佳顺序方法仍然难以捉摸。特别危险的患者是那些普遍存在室性心律失调或治疗期间骨密度增加较大的患者。为了更好地理解这些风险和策略,在denosumab后保存骨骼,一个新兴的转化和临床前工作正在揭示RANKL抑制和戒断的生物学。发现一种有效的“退出策略”来控制骨转换反弹,避免denosumab后的骨质流失,将提高患者和临床医生对这种高效且安全的骨质疏松症治疗方法的信心。这一观点描述了denosumab后反弹的临床问题,提供了对denosumab后使用双膦酸盐的人体研究的全面更新,并探讨了临床前研究的机制见解,这对设计最终的人体试验至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Denosumab discontinuation in the clinic: implications of rebound bone turnover and emerging strategies to prevent bone loss and fractures.

Denosumab discontinuation in the clinic: implications of rebound bone turnover and emerging strategies to prevent bone loss and fractures.

Denosumab discontinuation in the clinic: implications of rebound bone turnover and emerging strategies to prevent bone loss and fractures.

Denosumab discontinuation in the clinic: implications of rebound bone turnover and emerging strategies to prevent bone loss and fractures.

Denosumab is a highly effective treatment for osteoporosis, and its long-term use is associated with incremental gains in BMD and sustained fracture risk reduction. Stopping denosumab, however, results in a rebound increase in bone turnover, loss of treatment-associated BMD gains, and in the worst case, spontaneous vertebral fractures (VFs). Insights into the risk factors, the underlying mechanisms for rebound-associated bone loss, and true incidence of rebound VFs are emerging. Conventional strategies using bisphosphonates to mitigate post-denosumab rebound display mixed success. Bisphosphonates may preserve bone density following short-term denosumab but the optimal sequential approach after longer-term denosumab remains elusive. Patients at particular risk of are those with prevalent VFs or greater on-treatment BMD gains. To greater understand these risks and strategies to preserve bone after denosumab, an emerging body of translational and preclinical work is shedding new light on the biology of RANKL inhibition and withdrawal. Discovering an effective "exit strategy" to control rebound bone turnover and avoid bone loss after denosumab will improve confidence among patients and clinicians in this highly effective and otherwise safe treatment for osteoporosis. This perspective characterizes the clinical problem of post-denosumab rebound, provides a comprehensive update on human studies examining the use of bisphosphonates following denosumab and explores mechanistic insights from preclinical studies that will be critical in the design of definitive human trials.

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来源期刊
Journal of Bone and Mineral Research
Journal of Bone and Mineral Research 医学-内分泌学与代谢
CiteScore
11.30
自引率
6.50%
发文量
257
审稿时长
2 months
期刊介绍: The Journal of Bone and Mineral Research (JBMR) publishes highly impactful original manuscripts, reviews, and special articles on basic, translational and clinical investigations relevant to the musculoskeletal system and mineral metabolism. Specifically, the journal is interested in original research on the biology and physiology of skeletal tissues, interdisciplinary research spanning the musculoskeletal and other systems, including but not limited to immunology, hematology, energy metabolism, cancer biology, and neurology, and systems biology topics using large scale “-omics” approaches. The journal welcomes clinical research on the pathophysiology, treatment and prevention of osteoporosis and fractures, as well as sarcopenia, disorders of bone and mineral metabolism, and rare or genetically determined bone diseases.
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