(Young investigator award) Use of protonpump inhibitors and risk of hip fracture

Background: Evidence from observational studies suggests that use of protonpump inhibitors (PPIs) is associated with low bone mineral density and increased risk of hip fracture. Given the current evidence, a causal relationship would be supported by higher fracture risks after prolonged PPI use, especially after exposure periods exceeding 1 year. Objective: To examine the association between use of PPIs and the risk of hip fracture, with particular reference to long-term use. Design and Subjects: Using the population-based Dutch PHARMO (www.pharmo.nl) database, a case-control study was conducted. The study cohort included data from 6,763 cases aged 18 years and older with a first hip/femur fracture during enrolment (1991-2002). To each case, up to four controls were matched by age, gender and region. We adjusted our analysis for disease and drug history. Results: Current users of PPIs had an increased risk of hip fracture (adjusted [adj.] OR 1.20; 95% CI 1.04-1.40), which is in line with data from the UK and Denmark. However, hip fracture risk attenuated with prolonged PPI use (adj. ORs of 1.26 [95% CI 0.94-1.68] with PPI use of 3 months or less, 1.31 [95% CI 0.97-1.75] for use of 4-12 months, 1.18 [95% CI 0.92-1.52] for use of 1-3 years and 1.09 [95% CI 0.81-1.47] for exposure of >3 years). Conclusions: Current PPI use was associated with a 1.2- fold increased risk of hip fracture. However, the observed attenuation of hip fracture risk with longer durations of PPI use does not support a causal relationship between use of PPIs and risk of hip fracture.