Current Gastroenterology Reports

, Volume 12, Issue 6, pp 448–457 | Cite as

Association of Long-Term Proton Pump Inhibitor Therapy with Bone Fractures and Effects on Absorption of Calcium, Vitamin B12, Iron, and Magnesium

  • Tetsuhide Ito
  • Robert T. JensenEmail author


Proton pump inhibitors (PPI) are one of the most widely used classes of drugs. PPIs have a very favorable safety profile, and it is unusual for a patient to stop them because of side effects. However, with increasing numbers of patients chronically taking PPIs for gastroesophageal reflux disease and other common, persistent conditions, the long-term potential adverse effects are receiving increasing attention. An insufficiently studied area receiving much attention is the long-term effect of chronic acid suppression on the absorption of vitamins and nutrients. This increased attention results from the reported potential adverse effect of chronic PPI treatment leading to an increased occurrence of bone fractures. Interest in this area has led to examination of the effects of PPIs on calcium absorption/metabolism and numerous cohort, case-control, and prospective studies of their ability to affect bone density and cause bone fractures. In this article, these studies are systematically examined, as are studies of the effects of chronic PPI use on absorption of VB12, iron, and magnesium. Studies in each area have led to differing conclusions, but when examined systematically, consistent results of several studies support the conclusion that long-term adverse effects on these processes can have important clinical implications.


Proton pump inhibitor PPI Acid suppression H+K+ATPase inhibitor Omeprazole Lansoprazole Rabeprazole Pantoprazole Esomeprazole Hip fractures Vitamin B12 Cobalamin Iron deficiency anemia Hypomagnesemia Hypocalcemia Osteoporosis Zollinger-Ellison syndrome 



This work was partially supported by intramural funds of the National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.


No potential conflict of interest relevant to this article was reported.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Authors and Affiliations

  1. 1.Department of Medicine and Bioregulatory Science, Graduate School of Medical ScienceKyushu UniversityFukuokaJapan
  2. 2.Digestive Diseases Branch, National Institutes of Diabetes and Digestive and Kidney DiseasesNational Institutes of HealthBethesdaUSA

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