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Abstract：
BACKGROUND: The fracture risk of patients with chronic obstructive pulmonary disease (COPD) treated with inhaled corticosteroids is controversial. And some large-scale randomized controlled trials have not solved this problem. The purpose of our systematic review and meta-analysis including 44 RCTs is to reveal the effect of inhaled corticosteroids on the fracture risk of COPD patients.
METHODS: Two reviewers independently retrieved randomized controlled trials of inhaled corticosteroids or combinations of inhaled corticosteroids in the treatment of COPD from PubMed, Embase, Medline, Cochrane Library, and Web of Science. The primary outcome was a fracture event. This study was registered at PROSPERO (CRD42022366778).
RESULTS: Forty-four RCTs were performed in 87,594 patients. Inhaled therapy containing ICSs (RR, 1.19; 95%CI, 1.04-1.37; P = 0.010), especially ICS/LABA (RR, 1.30; 95%CI, 1.10-1.53; P = 0.002) and triple therapy (RR, 1.49; 95%CI, 1.03-2.17; P = 0.04) were significantly associated with the increased risk of fracture in COPD patients when compared with inhaled therapy without ICSs. Subgroup analyses showed that treatment duration ≥ 12 months (RR, 1.19; 95%CI, 1.04-1.38; P = 0.01), budesonide therapy (RR, 1.64; 95%CI., 1.07-2.51; P = 0.02), fluticasone furoate therapy (RR, 1.37; 95%CI, 1.05-1.78; P = 0.02), mean age of study participants ≥ 65 (RR, 1.27; 95%CI, 1.01-1.61; P = 0.04), and GOLD stage III(RR, 1.18; 95%CI, 1.00-1.38; P = 0.04) were significantly associated with an increased risk of fracture. In addition, budesonide ≥ 320 ug bid via MDI (RR, 1.75; 95%CI, 1.07-2.87; P = 0.03) was significantly associated with the increased risk of fracture.
CONCLUSIONS: Inhalation therapy with ICSs, especially ICS/LABA or triple therapy, increased the risk of fracture in patients with COPD compared with inhaled therapy without ICS. Treatment duration, mean age of participants, GOLD stage, drug dosage form, and drug dose participated in this association. Moreover, different inhalation devices of the same drug also had differences in risk of fracture.
METHODS: Two reviewers independently retrieved randomized controlled trials of inhaled corticosteroids or combinations of inhaled corticosteroids in the treatment of COPD from PubMed, Embase, Medline, Cochrane Library, and Web of Science. The primary outcome was a fracture event. This study was registered at PROSPERO (CRD42022366778).
RESULTS: Forty-four RCTs were performed in 87,594 patients. Inhaled therapy containing ICSs (RR, 1.19; 95%CI, 1.04-1.37; P = 0.010), especially ICS/LABA (RR, 1.30; 95%CI, 1.10-1.53; P = 0.002) and triple therapy (RR, 1.49; 95%CI, 1.03-2.17; P = 0.04) were significantly associated with the increased risk of fracture in COPD patients when compared with inhaled therapy without ICSs. Subgroup analyses showed that treatment duration ≥ 12 months (RR, 1.19; 95%CI, 1.04-1.38; P = 0.01), budesonide therapy (RR, 1.64; 95%CI., 1.07-2.51; P = 0.02), fluticasone furoate therapy (RR, 1.37; 95%CI, 1.05-1.78; P = 0.02), mean age of study participants ≥ 65 (RR, 1.27; 95%CI, 1.01-1.61; P = 0.04), and GOLD stage III(RR, 1.18; 95%CI, 1.00-1.38; P = 0.04) were significantly associated with an increased risk of fracture. In addition, budesonide ≥ 320 ug bid via MDI (RR, 1.75; 95%CI, 1.07-2.87; P = 0.03) was significantly associated with the increased risk of fracture.
CONCLUSIONS: Inhalation therapy with ICSs, especially ICS/LABA or triple therapy, increased the risk of fracture in patients with COPD compared with inhaled therapy without ICS. Treatment duration, mean age of participants, GOLD stage, drug dosage form, and drug dose participated in this association. Moreover, different inhalation devices of the same drug also had differences in risk of fracture.
摘要：
背景：吸入性糖皮质激素治疗慢性阻塞性肺疾病（COPD）患者的骨折风险存在争议。而一些大规模的随机对照试验并没有解决这个问题。我们的系统评价和荟萃分析包括44项随机对照试验的目的是揭示吸入糖皮质激素对COPD患者骨折风险的影响。
方法：两名评审者独立检索了PubMed的吸入糖皮质激素或吸入糖皮质激素组合治疗COPD的随机对照试验，Embase,Medline,科克伦图书馆,和WebofScience。主要结果是骨折事件。本研究在PROSPERO注册(CRD42022366778)。
结果：87,594例患者共进行了44项随机对照试验。含ICS的吸入疗法（RR，1.19；95CI，1.04-1.37；P=0.010），特别是ICS/LABA(RR，1.30；95CI，1.10-1.53；P=0.002）和三联疗法（RR，1.49；95CI，1.03-2.17；P=0.04）与COPD患者的骨折风险增加显著相关。亚组分析显示，治疗持续时间≥12个月(RR，1.19；95CI，1.04-1.38；P=0.01），布地奈德治疗（RR，1.64；95CI。,1.07-2.51；P=0.02），糠酸氟替卡松治疗(RR，1.37；95CI，1.05-1.78；P=0.02），研究参与者的平均年龄≥65岁(RR，1.27；95CI，1.01-1.61；P=0.04），和黄金阶段III(RR，1.18；95CI，1.00-1.38；P=0.04）与骨折风险增加显着相关。此外,布地奈德≥320ug通过MDI投标(RR，1.75；95CI，1.07-2.87；P=0.03）与骨折风险增加显着相关。
结论：用ICSs吸入治疗，尤其是ICS/LABA或三联疗法，与不使用ICS的吸入治疗相比,COPD患者的骨折风险增加.治疗持续时间,参与者的平均年龄，黄金舞台,药物剂型，和药物剂量参与了这个协会。此外，同一药物的不同吸入装置在骨折风险上也有差异。
方法：两名评审者独立检索了PubMed的吸入糖皮质激素或吸入糖皮质激素组合治疗COPD的随机对照试验，Embase,Medline,科克伦图书馆,和WebofScience。主要结果是骨折事件。本研究在PROSPERO注册(CRD42022366778)。
结果：87,594例患者共进行了44项随机对照试验。含ICS的吸入疗法（RR，1.19；95CI，1.04-1.37；P=0.010），特别是ICS/LABA(RR，1.30；95CI，1.10-1.53；P=0.002）和三联疗法（RR，1.49；95CI，1.03-2.17；P=0.04）与COPD患者的骨折风险增加显著相关。亚组分析显示，治疗持续时间≥12个月(RR，1.19；95CI，1.04-1.38；P=0.01），布地奈德治疗（RR，1.64；95CI。,1.07-2.51；P=0.02），糠酸氟替卡松治疗(RR，1.37；95CI，1.05-1.78；P=0.02），研究参与者的平均年龄≥65岁(RR，1.27；95CI，1.01-1.61；P=0.04），和黄金阶段III(RR，1.18；95CI，1.00-1.38；P=0.04）与骨折风险增加显着相关。此外,布地奈德≥320ug通过MDI投标(RR，1.75；95CI，1.07-2.87；P=0.03）与骨折风险增加显着相关。
结论：用ICSs吸入治疗，尤其是ICS/LABA或三联疗法，与不使用ICS的吸入治疗相比,COPD患者的骨折风险增加.治疗持续时间,参与者的平均年龄，黄金舞台,药物剂型，和药物剂量参与了这个协会。此外，同一药物的不同吸入装置在骨折风险上也有差异。
