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

The Osteoporosis Clinic, Aarhus Amtssygehus, Aarhus University Hospital, Tage Hansens Gade 2, DK-8000, Aarhus C, Denmark.
Calcified Tissue International (Impact Factor: 3.27). 09/2006; 79(2):76-83. DOI: 10.1007/s00223-006-0021-7
Source: PubMed


We studied the effect of proton pump inhibitors, histamine H(2) 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 H(2) antagonists, and other antacid drugs. Adjustments were made for several confounders, including diagnosis of an ulcer, nonsteroidal anti-inflammatory drug use, use of histamine H(1) 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 H(2) 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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Available from: Peter Vestergaard
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    • "PPIs have been widely used since their introduction in the late 1980s. Several large observational studies suggest that PPI use is associated with a modest increase in osteoporotic fracture risk [Yang et al. 2006; Yu et al. 2008; Vestergaard et al. 2006b; Targownik et al. 2008]. Based on these and two other studies, the US Food and Drug Administration revised labeling for PPIs in May 2010 to include information about the potential risk of hip, spinal, or radial fractures. "
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    • "Little is known on the effects of drugs affecting histamine signaling on the skeletal system in humans. The data on the effects of H 2 antagonists are conflicting [4] [5] [8] [18] [20] [43], and, to our knowledge, only one population-based study and one clinical study addressed the effect of H 1 antagonists on bone mineral density or content [18] [41]. "
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    • "Calcium solubilization is thought to be prerequisite for calcium absorption in the small intestine, with the stomach's acidic environment inducing the dissolution of calcium salts and the release of ionized calcium (Bo-Linn et al. 1984; Sipponen and Harkonen 2010). To this end, several clinical studies reported a positive association between the long-term use of acid suppressing agents and bone fractures (Vestergaard et al. 2006; Yang et al. 2006; Ito and Jensen 2010). Moreover, short and long-term use of acid suppressing agents decreased BMD (Adachi et al. 1998; Kinjo et al. 2008). "
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