Calcified Tissue International

, Volume 79, Issue 2, pp 76–83 | Cite as

Proton Pump Inhibitors, Histamine H2 Receptor Antagonists, and Other Antacid Medications and the Risk of Fracture

  • P. VestergaardEmail author
  • L. Rejnmark
  • L. Mosekilde


We studied the effect of proton pump inhibitors, histamine H2 receptor antagonists, and other types of antacid drugs on fracture risk. All cases were subjects with any fracture sustained during the year 2000 (n = 124,655). For each case, three controls (n = 373,962) matched on age and gender were randomly drawn from the background population. The primary exposure variables were use of proton pump inhibitors, histamine H2 antagonists, and other antacid drugs. Adjustments were made for several confounders, including diagnosis of an ulcer, nonsteroidal anti-inflammatory drug use, use of histamine H1 antagonists, stomach resection, previous fracture, and use of corticosteroids. The effect of dose was examined by stratifying for cumulated dose (defined daily dose). Use of proton pump inhibitors was associated with an increase in fracture risk for use within the last year [odds ratio (OR) = 1.18, 95% confidence interval (CI) 1.12–1.43 for overall fracture risk; OR = 1.45, 95% CI 1.28–1.65 for hip fractures; and OR = 1.60, 95% CI 1.25–2.04 for spine fractures). Histamine H2 antagonists were associated with a decreased fracture risk if they had been used within the last year (OR = 0.88, 95% CI 0.82–0.95 for any fracture, OR = 0.69, 95% CI 0.57–0.84 for hip fractures). Other antacids were not associated with overall fracture risk but were associated with hip and spine fractures. Proton pump inhibitors appeared to be associated with a limited increase in fracture risk, in contrast to histamine H 2 antagonists, which seemed to be associated with a small decrease in fracture risk. In all cases, the changes in risk estimates were small and the clinical significance was limited.


Proton pump inhibitor Histamine H2 receptor antagonist Antacid Fracture risk 



Danmarks Statistik (Statistics Denmark) is acknowledged for the help without which this project would not have been possible. Research Librarian Ms. Edith Clausen is acknowledged for invaluable help with the references. The Danish Medical Research Council granted financial support (grant 22-04-0495).


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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  1. 1.The Osteoporosis ClinicAarhus Amtssygehus, Aarhus University HospitalAarhus CDenmark
  2. 2.Department of Endocrinology and Metabolism CAarhus Amtssygehus, Aarhus University HospitalAarhus CDenmark

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