D'Andrea Elvira, Schneeweiss Sebastian, Franklin Jessica M, Kim Seoyoung C, Glynn Robert J, Lee Su Been, Wang Shirley V
Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Arthritis Rheumatol. 2025 Jan;77(1):12-21. doi: 10.1002/art.42968. Epub 2024 Sep 18.
The objective of this study is to evaluate the concordance of results between the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON)-Pivotal Fracture Trial (PFT) and a nonrandomized database study designed to emulate the trial.
HORIZON-PFT evaluated the efficacy of zoledronic acid versus placebo in reducing the risk of hip fractures and found a 41% risk reduction over a three-year treatment period (hazard ratio [HR] = 0.59; 95% confidence interval [95% CI] 0.42-0.83). Using two US claims databases from August 2007 to December 2020 or June 2021, we applied eligibility criteria from HORIZON-PFT and identified women with osteoporosis who initiated zoledronic acid or raloxifene as a proxy for placebo. The study protocol was registered on ClinicalTrials.gov (NCT04736693) before inferential analyses. We compared HORIZON-PFT and database study results using prespecified metrics.
Because of low adherence in clinical practice, on-treatment follow-up was truncated at 18 months in the database study. The hip fracture risk after 18 months was 9.3 in 1,000 in the trial and 8.3 in 1,000 in the database analysis. In the database study, zoledronic acid was associated with a 28% reduction in hip fractures risk compared with raloxifene (HR = 0.72; 95% CI 0.51-0.92). The attenuated effect of zoledronic acid in the database study may be explained by its shorter follow-up, because the interpolated estimate of the effect in HORIZON-PFT at 18 months was HR (randomized controlled trial), 0.74, nearly identical to the observational estimate HR 0.72.
Real-world emulation of the HORIZON-PFT found that zoledronic acid reduced hip fractures risk over an 18-month follow-up period. Limited adherence in clinical practice diminished the magnitude of its preventive effect and precluded long-term estimation of effectiveness in this setting.
本研究的目的是评估每年一次唑来膦酸治疗的健康结果与降低发病率（HORIZON）-关键骨折试验（PFT）和一项旨在模拟该试验的非随机数据库研究结果之间的一致性。
HORIZON-PFT评估了唑来膦酸与安慰剂相比在降低髋部骨折风险方面的疗效，发现在三年治疗期内风险降低了41%（风险比[HR]=0.59；95%置信区间[95%CI]0.42-0.83）。利用2007年8月至2020年12月或2021年6月的两个美国索赔数据库，我们应用了HORIZON-PFT的纳入标准，确定了开始使用唑来膦酸或雷洛昔芬作为安慰剂替代物的骨质疏松症女性。在进行推断分析之前，研究方案已在ClinicalTrials.gov（NCT04736693）上注册。我们使用预先指定的指标比较了HORIZON-PFT和数据库研究的结果。
由于临床实践中的依从性较低，数据库研究中的治疗期随访在18个月时被截断。试验中18个月后的髋部骨折风险为每1000人中有9.3例，数据库分析中为每1000人中有8.3例。在数据库研究中，与雷洛昔芬相比，唑来膦酸使髋部骨折风险降低了28%（HR=0.72；95%CI 0.51-0.92）。数据库研究中唑来膦酸效果减弱可能是由于随访时间较短，因为HORIZON-PFT在18个月时效果的内插估计值为HR（随机对照试验）0.74，与观察估计值HR 0.72几乎相同。
对HORIZON-PFT的真实世界模拟发现，唑来膦酸在18个月的随访期内降低了髋部骨折风险。临床实践中有限的依从性降低了其预防效果的幅度，并且无法在此环境中对有效性进行长期估计。
