Clinical Inquiries

What are the risks of long-term PPI use for GERD symptoms in patients > 65 years?

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Hip and vertebral fracture riskis associated with PPIs

A 2011 systematic review and meta-analysis investigated the risk of fracture in adult patients taking PPIs for any indication.4 The analysis included 10 observational studies (4 cohort, 6 case-control) with a total of 223,210 fracture cases. The authors examined the incidence of hip, vertebral, and wrist or forearm fractures.

No significant association was found between PPI use and wrist or forearm fracture (3 studies; pooled OR = 1.09; 95% CI, 0.95-1.24). A modest association was noted between PPI use and both hip fractures (9 trials; OR = 1.25; 95% CI, 1.14-1.37) and vertebral fractures (4 trials; OR = 1.5; 95% CI, 1.32-1.72).

Subgroup analysis didn’t reveal evidence of an effect of duration of PPI use on fracture. Investigators didn’t conduct subgroup analysis of different patient ages. Final results were limited by significant heterogeneity with an I2 of 86%.


A 2015 American Geriatrics Society Beers Criteria update recommends limiting PPI use because of increased risk of C difficile infections and fractures. It also recommends against using PPIs for longer than 8 weeks except for high-risk patients (such as patients taking oral corticosteroids or chronic nonsteroidal anti-inflammatory drug users), patients with Barrett’s esophagitis, or patients who need maintenance after failure of a drug discontinuation trial or H2 blockers (quality of evidence, high; SOR, strong).5

Editor’s takeaway: Despite limited evidence specific to patients over age 65, or perhaps because the majority of the studied populations were younger, increased caution should be exercised in the use of PPIs.

Evidence-based answers from the Family Physicians Inquiries Network

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