Background: Proton pump inhibitors (PPIs) are widely
used in elderly patients and are frequently coadministered
in users of oral bisphosphonates. Biologically, PPIs
could affect the absorption of calcium, vitamin B12, and
bisphosphonates and could affect the osteoclast proton
pump, thus interacting with bisphosphonate antifracture
efficacy. Moreover, PPIs themselves have been linked
to osteoporotic fractures.
Methods: Population-based, national register–based,
open cohort study of 38 088 new alendronate sodium users
with a mean duration of follow-up of 3.5 years. We
related risk of hip fracture to recent pharmacy records
of refill of prescriptions for alendronate.
Results: For hip fractures, there was statistically significant
interaction with alendronate for PPI use (P.05).
The treatment response associated with complete refill
compliance to alendronate was a 39% risk reduction (hazard
ratio [HR], 0.61; 95% confidence interval [CI], 0.52-
0.71; P.001) in patients who were not PPI users, while
the risk reduction in concurrent PPI users was not significant
(19%; HR, 0.81; 95% CI, 0.64-1.01; P=.06). The
attenuation of the risk reduction was dose and age dependent.
In contrast, there was no significant impact of
concurrent use of histamine H2 receptor blockers.
Conclusions: Concurrent PPI use was associated with
a dose-dependent loss of protection against hip fracture
with alendronate in elderly patients. This is an observational
study, so a formal proof of causality cannot be made,
but the dose-response relationship and the lack of impact
of prior PPI use provides reasonable grounds for discouraging
the use of PPIs to control upper gastrointestinal
tract complaints in patients treated with oral
bisphosphonates.