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


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.

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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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Correspondence to P. Vestergaard.

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Vestergaard, P., Rejnmark, L. & Mosekilde, L. Proton Pump Inhibitors, Histamine H2 Receptor Antagonists, and Other Antacid Medications and the Risk of Fracture. Calcif Tissue Int 79, 76–83 (2006).

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  • Proton pump inhibitor
  • Histamine H2 receptor antagonist
  • Antacid
  • Fracture risk