de Vries Frank, Pouwels Sander, Bracke Madelon, Leufkens Hubert G M, Cooper Cyrus, Lammers Jan-Willem J, van Staa Tjeerd-Pieter
Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
Pharmacoepidemiol Drug Saf. 2007 Jun;16(6):612-9. doi: 10.1002/pds.1318.
Administration of beta-2 agonists decreased bone mineral density in rats. But the association between bronchodilators and fracture risk has not been studied in humans.
To examine the association between use of beta-2 agonists and risk of hip/femur fracture.
We conducted a population-based case-control study (6763 cases) in the Dutch PHARMO database. Current beta-2 agonist use was compared to never use. We adjusted for severity of the underlying respiratory disease and disease and drug history.
A hospitalisation for asthma/COPD in the year before index date increased risk of hip/femur fracture: crude OR 2.17 (95% CI, 1.41-3.34). Patients using higher doses of beta-2 agonists had increased risk of hip/femur fracture: crude OR 1.94 (95% CI, 1.41-2.66) for daily dosages of >or=1600 microg albuterol equivalent. The excess fracture risk reduced after adjustment for disease severity (1.46; 95% CI, 1.02-2.08) and after exclusion of oral glucocorticoid users (1.31; 95% CI, 0.80-2.15). Risk of hip/femur fracture was similar between users of beta-2 agonists, inhaled glucocorticoids and anticholinergics.
We found increases in the risk of hip/femur fracture in patients using higher doses of beta-2 agonists. However, the excess risk of hip/femur fracture substantially reduced after exclusion of oral glucocorticoid users and after adjustment for the underlying disease. Risk of hip/femur fracture was similar between users of beta-2 agonists, inhaled glucocorticoids and anticholinergics. The severity of the underlying disease, rather than the use of beta-2 agonists, may play an important role in the aetiology of hip/femur fractures in patients using beta-2 agonists.
给予β-2激动剂可降低大鼠的骨矿物质密度。但支气管扩张剂与骨折风险之间的关联尚未在人类中进行研究。
研究β-2激动剂的使用与髋部/股骨骨折风险之间的关联。
我们在荷兰PHARMO数据库中进行了一项基于人群的病例对照研究（6763例病例）。将当前使用β-2激动剂的情况与从未使用的情况进行比较。我们对潜在呼吸系统疾病的严重程度以及疾病和用药史进行了校正。
在索引日期前一年因哮喘/慢性阻塞性肺疾病住院会增加髋部/股骨骨折的风险：粗比值比为2.17（95%可信区间，1.41 - 3.34）。使用较高剂量β-2激动剂的患者髋部/股骨骨折风险增加：对于每日剂量≥1600微克沙丁胺醇当量，粗比值比为1.94（95%可信区间，1.41 - 2.66）。在对疾病严重程度进行校正后（1.46；95%可信区间，1.02 - 2.08）以及排除口服糖皮质激素使用者后（1.31；95%可信区间，0.80 - 2.15），额外的骨折风险降低。β-2激动剂使用者、吸入性糖皮质激素使用者和抗胆碱能药物使用者的髋部/股骨骨折风险相似。
我们发现使用较高剂量β-2激动剂的患者髋部/股骨骨折风险增加。然而，在排除口服糖皮质激素使用者并对潜在疾病进行校正后，髋部/股骨骨折的额外风险大幅降低。β-2激动剂使用者、吸入性糖皮质激素使用者和抗胆碱能药物使用者的髋部/股骨骨折风险相似。在使用β-2激动剂的患者中，潜在疾病的严重程度而非β-2激动剂的使用可能在髋部/股骨骨折的病因中起重要作用。
