长期使用质子帮浦抑制剂会增加髋骨骨折风险


  【24drs.com】一篇新研究强调,长期使用质子帮浦抑制剂(PPIs)会增加停经后妇女的髋骨骨折风险,特别是有抽菸者。
  
  PPIs会增加胃泌素之分泌、抑制钙质吸收、改变破骨细胞功能而影响骨折风险,美国自2003年后,这些药物就可以开架式贩售,用来治疗消化不良,到了2010年5月,美国食品药物管理局提出警讯,广泛使用PPI和髋骨骨折有所关联,要求提供进一步的信息。
  
  在线登载于1月31日英国医学期刊上的新研究发表了近80,000名妇女的资料,波士顿麻州综合医院Hamed Khalili医师等人检视了「护士健康研究」这项研究的前瞻世代资料,该研究提供了生活型态与饮食风险因素的信息;这项研究始于1982年,每2年以问卷方式评估研究对象。
  
  该研究的79,899名妇女研究对象中,PPIs使用情况在2000-2008年间增加将近3倍,从6.7%增至18.9%;研究者在追踪的565,786人-年之间共发现有893例髋骨骨折。长期使用这类药物至少2年的妇女,髋骨骨折的绝对风险是每1000人-年为2.02件,没有使用这类药物的妇女则是每1000人-年为1.51件。
  
  使用PPIs 2年以上的妇女,髋骨骨折风险高出35%(年龄校正风险比为1.35;95%信心区间[CI]为1.13 - 1.62),校正身体质量指数、体能活动情况、钙质摄取、使用其它可能影响骨折风险的药物(例如双磷酸盐类、thiazide类利尿剂、皮质类固醇、荷尔蒙替代疗法)等之后,关联依旧成立。
  
  长期使用PPI与髋骨骨折风险有关。研究者报告指出,相较于未使用这类药物者,使用PPIs 2年的妇女发生骨折的完整校正风险比为1.36 (1.12 - 1.65)、使用4年者为1.42 (1.05 - 1.93)、使用6-8年者为1.55 (1.03 - 2.32),不过,停止服用这类药物至少2年后,风险值恢复到正常。
  
  抽菸史在考虑的风险因素中占首位,目前有抽菸或曾经抽菸妇女的骨折风险增加超过50% (完整校正风险比为1.51 [95% CI,1.20 - 1.91]),相对的,作者们发现从未抽菸者使用PPI和骨折风险并无关联(完整校正风险比为1.06 [95% CI,0.77 - 1.46]),研究者认为,抽菸会抑制钙质吸收,因而加重了PPIs增加骨折的风险,而使用PPI的原因并不会影响骨折风险。
  
  根据研究者指出,研究强度包括:前瞻式设计、样本数多、分析了几个公认的可能风险因素,研究限制是,未载明PPIs的品牌与计量;研究者结论指出,停经后妇女长期使用PPI与髋骨骨折风险增加有关,使用期间最久者或是有抽菸史的妇女,其风险最大。
  
  资料来源:http://www.24drs.com/professional/list/content.asp?x_idno=6718&x_classno=0&x_chkdelpoint=Y
  

Proton Pump Inhibitors Raise Hip Fracture Risk Over Time

By Ricki Lewis, PhD
Medscape Medical News

January 31, 2012 — A new study strengthens the association of long-term use of proton pump inhibitors (PPIs) with increased risk for hip fracture in postmenopausal women, particularly those who smoke.

PPIs can affect fracture risk by increasing secretion of gastrin, inhibiting calcium absorption, and altering osteoclast function. Use of these drugs to treat indigestion increased when they became available over the counter in the United States in 2003. In May 2010, the US Food and Drug Administration issued a warning about the possible link between extended PPI use and hip fracture and requested further information.

The new study, published online January 31 in the British Medical Journal, adds information from nearly 80,000 women to the body of data. Hamed Khalili, MD, from Massachusetts General Hospital, Boston, Massachusetts, and colleagues examined data from the prospective cohort Nurses' Health Study, which provided information on lifestyle and dietary risk factors. The study, which began in 1982, assesses participants by questionnaire every 2 years.

Use of PPIs increased nearly 3-fold from 2000 to 2008 among the 79,899 women in the study, from 6.7% to 18.9%. The researchers documented 893 hip fractures over 565,786 person-years of follow-up. Absolute risk for hip fracture among the women who regularly used the drugs for at least 2 years was 2.02 events per 1000 person years compared with 1.51 events per 1000 person years among women who did not take the drugs.

The risk for hip fracture among women who used PPIs for 2 or more years was 35% higher (age-adjusted hazard ratio, 1.35; 95% confidence interval [CI], 1.13 - 1.62). The association held up after adjusting for body mass index, physical activity level, calcium intake, and use of other drugs that can affect fracture risk, such as bisphosphonates, thiazide diuretics, corticosteroids, and hormone replacement.

Hip fracture risk correlated with PPI use over time. "Compared with non-users, the fully adjusted hazard ratios of fracture were 1.36 (1.12 - 1.65) for women with two years' use of PPIs, 1.42 (1.05 - 1.93) for four years' use, and 1.55 (1.03 - 2.32) for six to eight years' use," the researchers report. However, the risk returns to normal for women who have ceased taking the drugs for at least 2 years.

Smoking history stood out among the risk factors considered. Fracture risk rose by more than 50% for women who currently smoke or did so previously (fully-adjusted hazard ratio 1.51 [95% CI, 1.20 - 1.91]). By contrast, the authors found no association between PPI use and fracture risk in never smokers (fully-adjusted hazard ratio 1.06 [95% CI, 0.77 - 1.46]). The researchers suggest that the inhibition of calcium absorption from smoking may act synergistically with PPIs to increase fracture risk. The reason for PPI use did not affect fracture risk.

Strengths of the study, according to the investigators, include its prospective design, large sample, and analysis of several putative confounding risk factors. A limitation is that the study did not include brands and dosages of the PPIs. The researchers conclude that "regular use of PPI was associated with increased risk of hip fracture among postmenopausal women, with the strongest risk observed in individuals with the longest duration of use or with a history of smoking."

The authors have disclosed no relevant financial relationships.

BMJ. Published online January 31, 2012.

    
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