Huang Zhenna, Liao Tzu-Chi, Chuang Albert Tzu-Ming, Shao Shih-Chieh, Lange Jeff, Lin Tzu-Chieh, Kim Min, Lai Edward Chia-Cheng
Amgen Inc, Thousand Oaks, CA, USA.
School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Osteoporos Int. 2025 Mar;36(3):465-473. doi: 10.1007/s00198-024-07381-1. Epub 2025 Jan 8.
Most subjects in osteoporosis clinical trials were women with postmenopausal osteoporosis and while bridging studies (BMD endpoint) provide an expectation that osteoporosis medications will reduce fracture risk in men. This real-world study shows direct evidence of fracture risk reduction among men with osteoporosis (36% of hip fracture reduction with denosumab).
Direct evidence for fracture risk reduction of medications used among men with osteoporosis is very limited. This study aims to evaluate the real-world effectiveness of denosumab in reducing fracture risk.
This study included 13,797 men aged ≥ 50 years with osteoporosis who had initiated denosumab in Taiwan. Taiwan's National Health Insurance Research Database includes all Taiwan residents' complete health claim data. We compared incidence rates of clinical fractures between patients on denosumab 60 mg subcutaneously every 6 months (on-treatment) and patients ending therapy after one administration (off-treatment). Propensity score (PS) analysis, adjusting for measured differences at baseline covariates, was used to estimate the adjusted hazard ratio using a Cox proportion hazards model.
During follow-up, 248 hip fracture events occurred. The crude incidence rates of hip fracture were 1.13 events and 1.73 events per 100 person-years in on-treatment and off-treatment cohorts, respectively. After PS inverse probability of treatment weighting, the cohorts achieved balance in all 59 covariates. The hip fracture event rate was lower in on-treatment cohort versus off-treatment cohort by 36% (hazard ratio, 0.64 [95% CI 0.50-0.83]). A similar magnitude of risk reduction was observed in clinical vertebral and nonvertebral fractures. A series of sensitivity analysis, including a validation analysis using a-million individual health records, demonstrated that unmeasured confounders were not suggested to impact study result interpretation.
In this large, real-world study evaluating denosumab treatment among men with osteoporosis, the observed fracture risk reductions were consistent with the available risk reductions demonstrated in clinical trials among women with postmenopausal osteoporosis.
骨质疏松症临床试验中的大多数受试者是绝经后骨质疏松症女性，虽然桥接研究（骨密度终点）表明人们期望骨质疏松症药物能降低男性骨折风险。这项真实世界研究显示了骨质疏松症男性骨折风险降低的直接证据（地诺单抗使髋部骨折风险降低36%）。
骨质疏松症男性使用药物降低骨折风险的直接证据非常有限。本研究旨在评估地诺单抗在降低骨折风险方面的真实世界有效性。
本研究纳入了台湾13797名年龄≥50岁且已开始使用地诺单抗的骨质疏松症男性。台湾国民健康保险研究数据库包含所有台湾居民的完整健康理赔数据。我们比较了每6个月皮下注射60mg地诺单抗的患者（治疗中）与单次给药后结束治疗的患者（治疗后）临床骨折的发生率。倾向评分（PS）分析通过调整基线协变量的测量差异，使用Cox比例风险模型估计调整后的风险比。
随访期间，发生了248例髋部骨折事件。治疗中组和治疗后组髋部骨折的粗发病率分别为每100人年1.13例和1.73例。经过PS治疗权重逆概率分析后，两组在所有59个协变量上达到平衡。治疗中组的髋部骨折事件发生率比治疗后组低36%（风险比，0.64[95%CI 0.50 - 0.83]）。在临床椎体和非椎体骨折中也观察到了类似程度的风险降低。一系列敏感性分析，包括使用100万份个人健康记录的验证分析，表明未测量的混杂因素不影响研究结果的解释。
在这项评估地诺单抗治疗骨质疏松症男性的大型真实世界研究中，观察到的骨折风险降低与绝经后骨质疏松症女性临床试验中显示的可用风险降低一致。
