Zaheer Sarah, LeBoff Meryl, Lewiecki E Michael
Brigham and Women's Hospital , Boston, MA , USA.
Expert Opin Drug Metab Toxicol. 2015 Mar;11(3):461-70. doi: 10.1517/17425255.2015.1000860. Epub 2015 Jan 22.
Low trauma fractures due to osteoporosis are a major health concern worldwide. Despite the availability of many therapeutic compounds to reduce fracture risk, osteoporosis remains undertreated and the burden of osteoporotic fractures remains high. Denosumab is a novel agent that acts to reduce bone turnover, improve bone mineral density, and reduce fracture risk, offering a favorable efficacy and safety profile.
This review covers the pharmacology and major clinical trials with extension/post-marketing follow-up, including trials for all FDA-approved indications of denosumab to date.
Denosumab is an efficacious and safe osteoporosis treatment option, with current data from up to 8 years of continued use showing continued improvement in bone density with sustained fracture risk reduction. Safety profiles overall are similar to placebo, with no new safety concerns in extension trials, though a theoretical increased risk of infection exists with RANKL inhibition. Future considerations include safety of prolonged treatment beyond 8 years, and efficacy/fracture risk after discontinuation or with non-adherence, given the characteristic pharmacodynamic profile of denosumab.
骨质疏松导致的低创伤性骨折是全球主要的健康问题。尽管有多种治疗药物可降低骨折风险，但骨质疏松症的治疗仍不充分，骨质疏松性骨折的负担依然很高。地诺单抗是一种新型药物，可降低骨转换、提高骨密度并降低骨折风险，具有良好的疗效和安全性。
本综述涵盖了药理学及主要临床试验，并进行了扩展/上市后随访，包括迄今为止所有美国食品药品监督管理局（FDA）批准的地诺单抗适应症的试验。
地诺单抗是一种有效且安全的骨质疏松症治疗选择，目前长达8年的持续使用数据显示，骨密度持续改善，骨折风险持续降低。总体安全性与安慰剂相似，扩展试验中未出现新的安全问题，尽管抑制核因子κB受体活化因子配体（RANKL）理论上会增加感染风险。鉴于地诺单抗独特的药效学特征，未来需要考虑超过8年的长期治疗安全性，以及停药或不依从后的疗效/骨折风险。
