Characterization of and Risk Factors for the Acute-Phase Response after Zoledronic Acid
Characterization of and Risk Factors for the Acute-Phase Response after Zoledronic Acid
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DOI：
10.1210/jc.2010-0597
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发表时间：
2010-09-01
影响因子：
5.8
通讯作者：
Black, D. M.
中科院分区：
文献类型：
--
作者：
Reid, I. R.;Gamble, G. D.;Black, D. M.
背景：静脉注射氨基二膦酸盐通常会引起急性时相反应(APR)，但这种反应的确切成分，其频率，目的：本研究的目的是描述APR的特征，确定其发生的频率和发生的危险因素。设计：这项研究是一项来自大型随机试验的不良事件分析。背景：这是一项多中心的国际试验。患者：患者包括7765名患有骨质疏松症的绝经后妇女。干预：唑来膦酸每年5 mg或安慰剂。主要观察指标：用唑来膦酸输注后3d内发生的不良事件。结果：30多个不良事件在唑来膦酸组中明显更常见，并被认为共同构成APR。这些症状分为五组：发热；肌肉骨骼(疼痛和关节肿胀)；胃肠(腹痛、呕吐、腹泻)；眼部炎症；以及全身(包括疲劳、鼻咽炎、浮肿)。在第一次注射后，唑来膦酸组共有42.4%的患者出现了APR，而安慰剂组的这一比例为11.7%。所有APR成分均在1d内达到高峰，APR的中位持续时间为3d，90%的APR严重程度为轻至中度。逐步回归分析显示，APR在非日裔亚洲人、年轻受试者和非类固醇抗炎药物使用者中较常见，在吸烟者、糖尿病患者、以前口服双磷酸盐的患者和拉丁美洲人中较少见(均为P<；0.05)。结论：本分析确定了APR的新成分，并首次对其危险因素进行了评估。尽管APR的频率很高，但在本研究中，APR很少导致停止治疗。(临床内分泌代谢酶95：4380-4387,2010)
Context: Intravenous aminobisphosphonates often cause an acute-phase response (APR), but the precise components of this, its frequency, and the risk factors for its development have not been systematically studied.Objective: The objective of the study was to characterize the APR and determine its frequency and the risk factors for its development.Design: The study was an analysis of adverse events from a large randomized trial.Setting: This was a multicenter international trial.Patients: Patients included 7765 postmenopausal women with osteoporosis.Intervention: Zoledronic acid 5 mg annually or placebo was the intervention.Main Outcome Measure: Adverse events occurring within 3 d of zoledronic acid infusion were measured.Results: More than 30 adverse events were significantly more common in the zoledronic acid group and were regarded collectively as constituting an APR. These were clustered into five groups: fever; musculoskeletal (pain and joint swelling); gastrointestinal (abdominal pain, vomiting, diarrhea); eye inflammation; and general (including fatigue, nasopharyngitis, edema). A total of 42.4% of the zoledronic acid group had an APR after the first infusion, compared with 11.7% of the placebo group. All APR components had their peak onset within 1 d, the median duration of the APR was 3 d, and severity was rated as mild or moderate in 90%. Stepwise regression showed that APR was more common in non-Japanese Asians, younger subjects, and nonsteroidal antiinflammatory drug users and was less common in smokers, patients with diabetes, previous users of oral bisphosphonates, and Latin Americans (P < 0.05 for all).Conclusion: This analysis identifies new components of the APR and provides the first assessment of risk factors for it. Despite its frequency, APR rarely resulted in treatment discontinuation in this study. (J Clin Endocrinol Metab 95: 4380-4387, 2010)