Gastroenterology Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
BMJ. 2012 Jan 30;344:e372. doi: 10.1136/bmj.e372.
To examine the association between chronic use of proton pump inhibitors (PPIs) and risk of hip fracture.
Prospective cohort study.
Nurses' Health Study, which originally recruited from the 11 most populous states in the US.
79,899 postmenopausal women enrolled in the Nurses' Health Study who provided data on the use of PPIs and other risk factors biennially since 2000 and were followed up to 1 June 2008.
Incident hip fracture
During 565,786 person years of follow-up, we documented 893 incident hip fractures. The absolute risk of hip fracture among regular users of PPIs was 2.02 events per 1000 person years, compared with 1.51 events per 1000 person years among non-users. Compared with non-users, the risk of hip fracture among women who regularly used PPIs for at least two years was 35% higher (age adjusted hazard ratio 1.35 (95% confidence interval 1.13 to 1.62)), with longer use associated with increasing risk (P(trend)<0.01). Adjustment for risk factors, including body mass index, physical activity, and intake of calcium did not materially alter this association (hazard ratio 1.36 (1.13 to 1.63)). These associations were also not changed after accounting for reasons for PPI use. The relation between PPI use and fracture differed by smoking history (P(interaction)=0.03). Among current and former smokers, PPI use was associated with greater than 50% increase in risk of fracture, with a multivariate hazard ratio for fracture of 1.51 (1.20 to 1.91). In contrast, among women who never smoked there was no association (multivariate hazard ratio 1.06 (0.77 to 1.46)). In a meta-analysis of these results with 10 prior studies, the pooled odds ratio of hip fracture associated with PPI use was 1.30 (1.25 to 1.36).
Chronic use of PPIs is associated with increased risk of hip fracture, particularly among women with a history of smoking.
研究长期使用质子泵抑制剂（PPIs）与髋部骨折风险之间的关系。
前瞻性队列研究。
美国人口最多的 11 个州最初招募的护士健康研究。
79899 名绝经后妇女参加了护士健康研究，自 2000 年以来每两年提供一次关于 PPI 使用和其他危险因素的数据，并随访至 2008 年 6 月 1 日。
新发髋部骨折
在 565786 人年的随访期间，我们记录了 893 例髋部骨折。与非使用者相比，经常使用 PPIs 的患者髋部骨折的绝对风险为 2.02 例/1000 人年，而 1.51 例/1000 人年。与非使用者相比，至少连续使用 PPI 两年的女性髋部骨折风险增加 35%（年龄调整后的危险比 1.35（95%置信区间 1.13 至 1.62）），使用时间越长风险越高（P(trend)<0.01）。调整包括体重指数、身体活动和钙摄入量在内的危险因素并未显著改变这种关联（危险比 1.36（1.13 至 1.63））。在考虑了 PPI 使用的原因后，这些关联也没有改变。PPIs 使用与骨折之间的关系因吸烟史而异（P(interaction)=0.03）。在当前吸烟者和以前吸烟者中，PPI 使用与骨折风险增加 50%以上相关，骨折的多变量危险比为 1.51（1.20 至 1.91）。相比之下，在从不吸烟的女性中，两者没有关联（多变量危险比 1.06（0.77 至 1.46））。在对这些结果与 10 项先前研究进行的荟萃分析中，与 PPI 使用相关的髋部骨折的合并优势比为 1.30（1.25 至 1.36）。
长期使用质子泵抑制剂与髋部骨折风险增加相关，尤其是在有吸烟史的女性中。
