Background: Some recent reports suggest an increased risk of fractures with use of proton pump inhibitors (PPIs) and histamine type 2 receptor antagonists (H2RAs), although results are inconsistent and a causal relationship has yet to be proven. As these acid-suppressive drugs may have uncommon adverse effects on the central nervous system (CNS), such as dizziness, we investigated whether their use is associated with falls as a possible mechanism for increasing fracture risk.
Methods: A cohort study with nested case-control analysis and two validation strategies was performed using data from UK patients (aged 40–89 years) included in The Health Improvement Network database (2000–2008). Due to the large number of falls, a random sample of 20,000 cases was used for the analysis.
Results: The overall incidence of falls per 1000 person-years was 13.0 (95% confidence interval [CI] = 12.9–13.1). After adjustment for potential confounders, there was no relationship between falls and current use of single PPIs (odds ratio [OR] = 0.95; 95% CI = 0.89–1.02) or H2RAs (OR = 1.01; 95% CI = 0.90–1.14); there was no relationship with dose or duration of treatment. Falls were associated with CNS disorders and treatment with various pharmacological agents including antiparkinson drugs (OR = 2.7; 95% CI = 2.2–3.3) and antiepileptics (OR = 2.1; 95% CI = 1.8–2.3).
Conclusions: There was no association between falls and use of PPIs or H2RAs. Any potential increase in the risk of fractures proposed to be associated with the use of acid-suppressive drugs is not via an increased risk of falls.
From the aSpanish Centre for Pharmacoepidemiologic Research (CEIFE), Madrid, Spain; and bAstraZeneca R&D, Mölndal, Sweden.
L.C.-S. and L.A.G.R. work for CEIFE, which has received research funding from AstraZeneca R&D, Mölndal, Sweden. L.A.G.R. has received honoraria for serving on scientific advisory boards for AstraZeneca. S.J. is an employee of AstraZeneca R&D, Mölndal, Sweden.
The study was funded in part with financial research support from AstraZeneca R&D, Mölndal, Sweden.
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Correspondence: Lucía Cea-Soriano, Centro Español de Investigación Farmacoepidemiológica (CEIFE), c/Almirante 28-2°, Madrid 28004, Spain. E-mail: firstname.lastname@example.org.
Received September 25, 2012
Accepted February 15, 2013