Clinical research studyProton Pump Inhibitors and Risk of Fractures: A Meta-Analysis of 11 International Studies
Section snippets
Eligibility Criteria
Methods of the analysis were prespecified in a protocol. To be eligible, studies had to examine the risk of bone fracture attributable to the use of proton pump inhibitors or histamine2-receptor antagonists, and include a comparator control group. Medication use had to be documented before occurrence of fracture. Analyses had to be adjusted at minimum for age and gender.
Search Strategy
PubMed/MEDLINE (National Center for Biotechnology Information), EMBASE (Elsevier), Web of Science (ISI Web of Knowledge), and
Study Selection
The systematic search of MEDLINE, EMBASE, and other sources provided a total of 642 citations, after adjusting for duplicates. Of these, 573 were excluded after initial abstract screening. The full texts of the remaining 69 articles were examined in more detail. Twelve publications met inclusion criteria;8, 9, 10, 11, 12, 14, 15, 16, 17, 18, 20, 21 however, 3 of these analyzed the same database (General Practice Research Database [GPRD]);8, 15, 17 only 1 was included in the meta-analysis to
Discussion
In this study level meta-analysis, proton pump inhibitor use was associated with a modestly increased risk of hip fractures. Spine fractures were more frequent among individuals taking proton pump inhibitors, and there also was a slight increase in risk of any-site fractures. These findings were similar in both men and women. Although the FDA advisory based on non-quantitative review of the data states that “patients at highest risk for fractures … used a PPI for one year or more,”13 our
Conclusions
This meta-analysis of observational studies found that proton pump inhibitor use modestly increased the risk of hip, spine, and any-site fractures, whereas histamine2-receptor antagonist use was not associated with increased fracture risk. The biologic mechanism is not yet clear, and we cannot rule out the possibility of residual confounding. But even a slight increase in fracture risk due to proton pump inhibitors may lead to a large number of additional fractures on a public health scale. The
Acknowledgments
The authors thank Dr Yu-Xiao Yang, Dr Douglas Corley, Dr Shelley Gray, Dr Laure Gossec, Dr Frank de Vries, Dr Peter Vestergaard, and Terri Blackwell for providing additional data for this meta-analysis.
References (45)
- et al.
Long-term safety concerns with proton pump inhibitors
Am J Med
(2009) - et al.
Proton pump inhibitors and histamine-2 receptor antagonists are associated with hip fractures among at-risk patients
Gastroenterology
(2010) - et al.
Meta-analysis in clinical trials
Control Clin Trials
(1986) - et al.
Proton pump inhibitor use is not associated with osteoporosis or accelerated bone mineral density loss
Gastroenterology
(2010) - et al.
Effects of proton pump inhibitors on calcium carbonate absorption in women: a randomized crossover trial
Am J Med
(2005) - et al.
Do acid-lowering agents affect vitamin B12 status in older adults?
J Am Med Dir Assoc
(2008) - et al.
A case-control study on adverse effects: H2 blocker or proton pump inhibitor use and risk of vitamin B12 deficiency in older adults
J Clin Epidemiol
(2004) Top-line Industry Data: 2009 U.S. Sales and Prescription Information. IMS Health Incorporated
- et al.
Long-term gastroesophageal reflux disease therapy improves reflux symptoms in elderly patients: five-year prospective study in community medicine
J Gastroenterol Hepatol
(2007) - et al.
Proton pump inhibitors and risk for recurrent Clostridium difficile infection
Arch Intern Med
(2010)
Proton-pump inhibitor use and the risk for community-acquired pneumonia
Ann Intern Med
Acid-suppressive medication use and the risk for hospital-acquired pneumonia
JAMA
Review article: potential gastrointestinal effects of long-term acid suppression with proton pump inhibitors
Aliment Pharmacol Ther
Long-term proton pump inhibitor therapy and risk of hip fracture
JAMA
Proton pump inhibitors, histamine H2 receptor antagonists, and other antacid medications and the risk of fracture
Calcif Tissue Int
Acid-suppressive medications and risk of bone loss and fracture in older adults
Calcif Tissue Int
Use of proton pump inhibitors and risk of osteoporosis-related fractures
CMAJ
Possible increased risk of fractures of the hip, wrist, and spine with the use of proton pump inhibitors
Proton pump inhibitor use, hip fracture, and change in bone mineral density in postmenopausal women: results from the Women's Health Initiative
Arch Intern Med
Proton pump inhibitor use and risk of hip fractures in patients without major risk factors
Pharmacotherapy
Increase in vertebral fracture risk in postmenopausal women using omeprazole
Calcif Tissue Int
Fracture risk in patients receiving acid-suppressant medication alone and in combination with bisphosphonates
Osteoporosis Int
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Funding: Dr Bauer is supported by National Institutes of Health Grant K24 ARO51895.
Conflict of Interest: None.
Authorship: All authors had access to the data and played a role in writing this manuscript.