The relationship between long-term proton pump inhibitor therapy and skeletal frailty
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MINI REVIEW
The relationship between long-term proton pump inhibitor therapy and skeletal frailty Arthur N. Lau1 • Michael Tomizza2 • Matthew Wong-Pack2 • Alexandra Papaioannou3 Jonathan D. Adachi1
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Received: 5 September 2014 / Accepted: 9 March 2015 Ó Springer Science+Business Media New York 2015
Abstract Proton pump inhibitors (PPIs) are a commonly prescribed class of medications. Their use has been associated with an increased rate of fractures, most notably hip fractures. However, there does not seem to be a clear association between PPI use and bone mineral density measurements, assessed by dual X-ray absorptiometry. The mechanism by which PPI use increases the risk of fractures remains unclear. This review will summarize the current evidence on this topic. Keywords Proton-pump inhibitors Fractures Osteoporosis Fragility
Introduction Proton pump inhibitors (PPIs) are one of the most commonly prescribed classes of medications worldwide. They are commonly used in the treatment of gastric esophageal reflux disease (GERD) and peptic ulcer disease, and serves as an effective prophylactic agent in patients treated concurrently with a non-steroidal anti-inflammatory drug (NSAID). PPIs act through irreversibly inhibiting the activity of Na?/K?/H? pumps located on parietal cells of the gastric lumen, thus preventing the secretion of & Arthur N. Lau [email protected] 1
Division of Rheumatology, Department of Medicine, McMaster University, Hamilton, Canada
2
Faculty of Health Sciences, McMaster University, Hamilton, Canada
3
Division of Geriatrics, Department of Medicine, McMaster University, Hamilton, Canada
hydrogen ions into the gastric lumen [1]. As such, PPIs are able to raise the pH level of the gastric lumen, and prevent associated complications seen with such an acidic environment. Many patients are prescribed a PPI on a chronic basis, since GERD, the most common reason for requiring a PPI, is a chronic condition, and long-term continued therapy with a PPI is required to suppress the symptoms. PPIs, as a class, are generally regarded as a safe medication and are well tolerated by patients. The rate of drug discontinuation due to an adverse event from PPI use ranges from 1 to 2 % [2]. Increasing evidence has revealed a number of complications associated with prolonged PPI use. These complications include an increased risk of community- acquired pneumonia [3, 4], Clostridium difficile infection [5, 6], vitamin B12 deficiency [7], and acute interstitial nephritis. In addition, PPIs have been associated with a negative effect on bone mineral metabolism, with a subsequent decline in bone mineral density (BMD) and an associated increase risk of fractures. This article will review the current evidence assessing the effect that PPI therapy has on BMD and fracture risk in addition to proposed mechanisms by which PPI use may have a negative impact on bone mineral metabolism.
Potential mechanisms The exact mechanism by which PPI use results in a decline in BMD and resultant increase in fracture risk
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