关键词： AFF, Atypical femoral fracture BM, Bone metastasis BMFS, BM-free survival BP, Bisphosphonate BTA, Bone-targeting agent Bone metastasis CI, Confidence interval Denosumab Efficacy HR, Hazard ratio HRQoL, Health-related quality of life IMWG, International Myeloma Working Group MM, Multiple myeloma MVF, Multiple vertebral fracture NSCLC, Non–small-cell lung cancer ONJ, Osteonecrosis of the jaw OPG, Osteoprotegerin OS, Overall survival PFS, Progression-free survival Q12W, Every 12 weeks Q4W, Every 4 weeks RANKL, Receptor activator of nuclear factor-κB ligand SC, Subcutaneous SRE, Skeletal-related event Safety Skeletal-related events uNTx/Cr, Urinary N-telopeptide normalized to urinary creatinine AFF, Atypical femoral fracture BM, Bone metastasis BMFS, BM-free survival BP, Bisphosphonate BTA, Bone-targeting agent Bone metastasis CI, Confidence interval Denosumab Efficacy HR, Hazard ratio HRQoL, Health-related quality of life IMWG, International Myeloma Working Group MM, Multiple myeloma MVF, Multiple vertebral fracture NSCLC, Non–small-cell lung cancer ONJ, Osteonecrosis of the jaw OPG, Osteoprotegerin OS, Overall survival PFS, Progression-free survival Q12W, Every 12 weeks Q4W, Every 4 weeks RANKL, Receptor activator of nuclear factor-κB ligand SC, Subcutaneous SRE, Skeletal-related event Safety Skeletal-related events uNTx/Cr, Urinary N-telopeptide normalized to urinary creatinine

来  源：   DOI：10.1016/j.jbo.2022.100416   PDF(Pubmed)

Abstract：
Skeletal-related events (SREs) are complications of bone metastases and carry a significant patient and economic burden. Denosumab is a receptor activator of nuclear factor-κB ligand (RANKL) inhibitor approved for SRE prevention in patients with multiple myeloma and patients with bone metastases from solid tumors. In phase 3 trials, denosumab showed superiority to the bisphosphonate zoledronate in reducing the risk of first on-study SRE by 17% (median time to first on-study SRE delayed by 8.2 months) and the risk of first and subsequent on-study SREs by 18% across multiple solid tumor types, including some patients with multiple myeloma. Denosumab also improved pain outcomes and reduced the need for strong opioids. Additionally, a phase 3 trial showed denosumab was noninferior to zoledronate in delaying time to first SRE in patients with newly diagnosed multiple myeloma. Denosumab has a convenient 120 mg every 4 weeks recommended dosing schedule with subcutaneous administration. Rare but serious toxicities associated with denosumab include osteonecrosis of the jaw, hypocalcemia, and atypical femoral fracture events, with multiple vertebral fractures reported following treatment discontinuation. After a decade of real-world clinical experience with denosumab, we are still learning about the optimal use and dosing for denosumab. Despite the emergence of novel and effective antitumor therapies, there remains a strong rationale for the clinical utility of antiresorptive therapy for SRE prevention. Ongoing studies aim to optimize clinical management of patients using denosumab for SRE prevention while maintaining safety and efficacy.
摘要：
骨骼相关事件（SRE）是骨转移的并发症，具有严重的患者和经济负担。Denosumab是核因子-κB配体（RANKL）抑制剂的受体激活剂，已被批准用于多发性骨髓瘤患者和实体瘤骨转移患者的SRE预防。在第三阶段试验中，denosumab在将首次研究SRE的风险降低17％（首次研究SRE的中位时间延迟8.2个月）和首次和随后的研究SRE的风险降低18％的优势多种实体瘤类型，包括一些多发性骨髓瘤患者。Denosumab还改善了疼痛结果，减少了对强效阿片类药物的需求。此外,一项3期试验显示,在新诊断的多发性骨髓瘤患者中,denosumab在延迟至首次SRE的时间方面不劣于唑来膦酸.Denosumab每4周有一个方便的120mg推荐的皮下给药方案。与denosumab相关的罕见但严重的毒性包括颌骨坏死，低钙血症,和非典型股骨骨折事件，治疗中断后报告多处椎骨骨折。在denosumab十年的真实世界临床经验之后，我们仍在学习denosumab的最佳使用和剂量。尽管出现了新颖有效的抗肿瘤疗法，抗吸收治疗预防SRE的临床应用仍有很强的理由.正在进行的研究旨在优化使用denosumab预防SRE的患者的临床管理，同时保持安全性和有效性。
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