Proton pump inhibitors and risk of fracture: a systematic review and meta-analysis of observational studies

Saowanee Ngamruengphong, Grigorios I Leontiadis, Saba Radhi, Andrew Dentino, Kenneth Nugent
American Journal of Gastroenterology 2011, 106 (7): 1209-18; quiz 1219

OBJECTIVES: Proton pump inhibitors (PPIs) are widely used in several acid-related gastrointestinal disorders. In vivo studies have suggested that gastric suppression by PPIs could result in decreased intestinal calcium absorption. Subsequently, there have been concerns that the chronic use of a PPI is associated with an increased risk of bone fracture. However, the results of clinical studies are conflicting.

METHODS: We performed a systematic review and meta-analysis of controlled observational studies to evaluate the risks of PPI use on fracture outcome. All controlled observational studies that compared fracture outcome in patients with PPI therapy with a control group were included. We calculated pooled odds ratios (ORs) using a random-effects model.

RESULTS: Of 1,668 identified studies, 10 (4 cohort and 6 case-control) with 223,210 fracture cases were included in our analysis. In PPI users, compared with non/past users, the OR for hip fracture (n=9) was 1.25 (95% confidence interval (CI)=1.14-1.37). The OR for vertebral fracture (n=4) was 1.50 (95% CI=1.32-1.72) and for wrist/forearm fracture (n=3) was 1.09 (95% CI=0.95-1.24). In subgroup analysis of hip fracture, this association was observed in both high-dose and low-dose PPI exposure. When stratified by duration of exposure, the short duration of PPI use was associated with increased risk of developing hip fracture (OR=1.24; 95% CI=1.19-1.28), whereas there was no significant increase in risk of hip fracture in long-term PPI users (OR=1.30; 95% CI=0.98-1.70). There was significant statistical and clinical heterogeneity among studies for the main analysis and most of the subgroup analyses.

CONCLUSIONS: Our results should be interpreted with caution. We found a modest association between PPI use and increased risk of hip and vertebral fractures, but no evidence of duration effect in subgroup analysis. However, observational studies cannot clarify whether the observed epidemiologic association is a causal effect or a result of unmeasured/residual confounding. Thus, randomized controlled studies are required to confirm or refute these results.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"