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Am J Gastroenterol. 2009 Mar;104 Suppl 2:S21-6. doi: 10.1038/ajg.2009.48.

Proton pump inhibitors and bone fractures?

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Keck School of Medicine, University of Southern California, Los Angeles, California, USA.


The objective of this study was to critically assess studies regarding proton pump inhibitors (PPIs) and fractures. A MEDLINE search was conducted to identify relevant articles. Three case-control studies assessed fractures and PPI use. A study of all subjects with fracture in Denmark in 2000 revealed adjusted OR=1.18 (1.12-1.43) for PPI use within the last year (hip fracture OR=1.45,1.28-1.65); no dose-response relationship was identified. A study of hip fractures in UK patients > or =50 years found adjusted OR=1.44 (1.30-1.59) for >1 year of PPIs; duration and average daily dose were significantly associated with fracture risk: adjusted OR for >1.75 times average daily dose for >1 year was 2.65 (1.80-3.90). A study of vertebral, wrist, and hip fractures in Manitoba patients > or =50 years found adjusted OR=0.99 (0.90-1.11) for > or =1 year of continuous PPI; association became significant > or =7 years (OR=1.92, 1.16-3.18). Consistency of some positive results in all studies, the dose and/or duration response in two studies, the possibility that acid inhibition may decrease calcium absorption, and association with histamine(2)-receptor antagonists in some studies support a causal association. The low magnitude of the association (ORs<2), lack of dose-response in one study, lack of association with histamine(2)-receptor antagonists in one study, lack of experimental evidence documenting a mechanism, and inability to assess potential confounding factors limit statements regarding causality. As with all medications, PPIs should be used for appropriate indications and not in higher doses or longer durations than necessary to achieve the desired outcomes.

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