title: Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: a prospective cohort study.
abstract: OBJECTIVE
  To examine the association between chronic use of proton pump inhibitors (PPIs) and risk of hip fracture.
  
  
  METHODS
  Prospective cohort study.
  
  
  METHODS
  Nurses' Health Study, which originally recruited from the 11 most populous states in the US.
  
  
  METHODS
  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.
  
  
  METHODS
  Incident hip fracture
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Chronic use of PPIs is associated with increased risk of hip fracture, particularly among women with a history of smoking.
authors.affiliation: Gastroenterology Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Hamed
authors.initials: H
authors.lastname: Khalili
authors.forename: Edward S
authors.initials: ES
authors.lastname: Huang
authors.forename: Brian C
authors.initials: BC
authors.lastname: Jacobson
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Camargo
authors.forename: Diane
authors.initials: D
authors.lastname: Feskanich
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chan
mesh_terms: D000328:Adult; D004032:Diet / Q000706:statistics & numerical data*; D005260:Female; D006620:Hip Fractures / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D008019:Life Style; D008875:Middle Aged; D009726:Nurses / Q000706:statistics & numerical data; D017698:Postmenopause; D016016:Proportional Hazards Models; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology
chemical_list: D054328:Proton Pump Inhibitors