Article

Use of proton pump inhibitors and risk of osteoporosis-related fractures. CMAJ

Department of Gastroenterology, Division of Internal Medicine, University of Manitoba, Winnipeg, Man.
Canadian Medical Association Journal (Impact Factor: 5.81). 09/2008; 179(4):319-26. DOI: 10.1503/cmaj.071330
Source: PubMed

ABSTRACT The use of proton pump inhibitors has been associated with an increased risk of hip fracture. We sought to further explore the relation between duration of exposure to proton pump inhibitors and osteoporosis-related fractures.
We used administrative claims data to identify patients with a fracture of the hip, vertebra or wrist between April 1996 and March 2004. Cases were each matched with 3 controls based on age, sex and comorbidities. We calculated adjusted odds ratios (OR) for the risk of hip fracture and all osteoporosis-related fractures for durations of proton pump inhibitor exposure ranging from 1 or more years to more than 7 years.
We matched 15 792 cases of osteoporosis-related fractures with 47 289 controls. We did not detect a significant association between the overall risk of an osteoportic fracture and the use of proton pump inhibitors for durations of 6 years or less. However, exposure of 7 or more years was associated with increased risk of an osteoporosis-related fracture (adjusted OR 1.92, 95% confidence interval [CI] 1.16-3.18, p = 0.011). We also found an increased risk of hip fracture after 5 or more years of exposure (adjusted OR 1.62, 95% CI 1.02-2.58, p = 0.04), with even higher risk after 7 or more years exposure (adjusted OR 4.55, 95% CI 1.68-12.29, p = 0.002).
Use of proton pump inhibitors for 7 or more years is associated with a significantly increased risk of an osteoporosis-related fracture. There is an increased risk of hip fracture after 5 or more years exposure. Further study is required to determine the clinical importance of this finding and to determine the value of osteoprotective medications for patients with long-term use of proton pump inhibitors.

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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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    • "A study conducted in Canada determined that after seven years of continuous exposure to a PPI, there was a statistically significant increase in osteoporosis-related fractures, and an increase risk of hip fracture after five years. [9] As bone mineralization and resorption takes many years, and because of the subtle effect that proton pump inhibitors have on bone mineralization, several years may be required before it has a measurable clinical outcome. "
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    • "Both the dose and the duration of proton pump inhibitors were associated with higher risk of hip fracture in patients in the General Practitioners' Research Database (Yang et al. 2006). Use of a proton-pump inhibitor for 7 or more years was associated with double the risk of osteoporotic fracture and a 5-times higher risk of hip fracture, and use for 5 or more years was associated with double the risk of hip fracture (Targownik et al. 2008). Another study found that use of a proton-pump inhibitor in the previous year was associated with increased fracture risk (18%, 45%, and 60% higher odds for overall fracture, hip fracture, and spine fracture risk, respectively) (Vestergaard et "
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