Proton Pump Inhibitors and Risk of Fractures: A Meta-Analysis of 11 International Studies

Endocrine Unit, Massachusetts General Hospital, Boston, USA.
The American journal of medicine (Impact Factor: 5). 06/2011; 124(6):519-26. DOI: 10.1016/j.amjmed.2011.01.007
Source: PubMed


Concerns have been raised about the risk of fractures with acid-suppressive medications, such as proton pump inhibitors and histamine(2)-receptor antagonists.
This meta-analysis evaluated the association between proton pump inhibitor or histamine(2)-receptor antagonist use and fractures. We performed a systematic search of published literature (1970 to October 10, 2010) in MEDLINE, EMBASE, and other sources. Ten publications reporting 11 studies were considered eligible for analysis.
All studies were observational case-control or cohort studies and primarily evaluated older adults. The summary effect estimate for risk of hip fracture increased modestly among individuals taking proton pump inhibitors (relative risk [RR] 1.30, 95% confidence interval [CI], 1.19-1.43). There also was an increase in spine (RR 1.56, 95% CI, 1.31-1.85) and any-site fractures (RR 1.16, 95% CI, 1.04-1.30) among proton pump inhibitor users. These findings were similar in both men and women and after stratification by duration of use. In contrast, histamine(2)-receptor antagonist use was not significantly associated with increased risk of hip fracture (RR 1.12, 95% CI, 0.97-1.30).
In this meta-analysis of observational studies, proton pump inhibitors modestly increased the risk of hip, spine, and any-site fractures, whereas histamine(2)-receptor antagonists were not associated with fracture risk. The possibility of residual confounding cannot be excluded. Further skeletal evaluation should be considered for patients who are taking proton pump inhibitors and also at risk for osteoporotic fracture.

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    • "Thus, fracture risk is dependent on duration of therapy [Corley et al. 2010]. PPI dose effects are difficult to quantitatively analyze because of incompatible definitions of doses among the studies; however, several studies have shown that fracture risk is increased when high doses are given compared with lower doses [Yu et al. 2011]. However, a recent meta-analysis found an association of hip fracture with both high- and low-dose PPI exposure [Ngamruengphong et al. 2011]. "
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    ABSTRACT: Drug-induced osteoporosis is a significant health problem and many physicians are unaware that many commonly prescribed medications contribute to significant bone loss and fractures. In addition to glucocorticoids, proton pump inhibitors, selective serotonin receptor inhibitors, thiazolidinediones, anticonvulsants, medroxyprogesterone acetate, aromatase inhibitors, androgen deprivation therapy, heparin, calcineurin inhibitors, and some chemotherapies have deleterious effects on bone health. Furthermore, many patients are treated with combinations of these medications, possibly compounding the harmful effects of these drugs. Increasing physician awareness of these side effects will allow for monitoring of bone health and therapeutic interventions to prevent or treat drug-induced osteoporosis.
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    • "For example, epidemiological evidence has associated renal failure with the use of nonselective NSAIDs [92] [93] [94] [95] [96]. Very recently, two studies linked proton pump inhibitors to increased fracture and CV risks [97] [98]. A large recent study associated significantly higher mortality with opioid misuse [99]. "

    Full-text · Article · Dec 2013 · Value in Health
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    • "A meta-analysis of 11 observational studies showed a mild increased risk of hip and vertebral fractures in PPI users of both sexes, compared to H2RA users [24]. Interestingly, the results were stronger in older participants and confirmed in a recent meta-analysis [24] [25]. "
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