Proton pump inhibitors and bone fractures?

Area of Science:

• Pharmacology
• Epidemiology
• Bone Health

Background:

• Proton pump inhibitors (PPIs) are widely prescribed for acid-related gastrointestinal disorders.
• Concerns exist regarding potential adverse effects of long-term PPI use, including an increased risk of bone fractures.
• The relationship between PPIs and fracture risk requires critical evaluation.

Purpose of the Study:

• To critically assess existing studies investigating the association between proton pump inhibitors (PPIs) and fracture risk.
• To evaluate the consistency, dose-response, and duration-response relationships in the identified studies.
• To determine the strength of evidence supporting a causal link between PPI use and fractures.

Main Methods:

• A comprehensive MEDLINE search was conducted to identify relevant case-control studies.
• Three case-control studies examining fractures in Denmark, the UK, and Manitoba were analyzed.
• Data on fracture incidence, PPI use (duration, dosage), and other relevant factors were extracted and assessed.

Main Results:

• Studies showed varied results, with some indicating an increased odds ratio (OR) for fractures associated with PPI use (e.g., OR=1.18 for hip fracture in Denmark).
• Two studies identified a dose- and/or duration-dependent relationship, with higher doses or longer use correlating with increased fracture risk (e.g., OR=2.65 for >1.75x dose for >1 year).
• However, one study found no significant association with continuous PPI use for up to 7 years (OR=0.99), and dose-response was not consistently identified across all studies.

Conclusions:

• Some evidence suggests a potential causal association between PPIs and fractures, supported by consistent findings, dose-response relationships in some studies, and potential mechanisms like reduced calcium absorption.
• Limitations including low magnitude of association (ORs<2), lack of consistent dose-response, absence of experimental evidence, and potential confounding factors restrict definitive conclusions on causality.
• Proton pump inhibitors should be prescribed for appropriate indications, using the lowest effective doses and shortest necessary durations to minimize potential risks.