Proton Pump Inhibitors, Histamine-2 Receptor Antagonists, and Hip Fracture Risk among Patients on Hemodialysis

Clin J Am Soc Nephrol. 2018 Oct 8;13(10):1534-1541. doi: 10.2215/CJN.02190218. Epub 2018 Sep 27.


Background and objectives: An association between proton pump inhibitor (PPI) use and hip fracture risk has been described in the general population, where the primary causative hypothesis focuses on impaired gastrointestinal calcium absorption. The impact of acid suppressor use on hip fracture risk in a high-risk subset, patients with ESKD requiring hemodialysis, is unknown and could help further distinguish the reason for higher susceptibility among PPI users.

Design, setting, participants, & measurements: Using the US Renal Data System, we identified all hip fracture events recorded between 2009 and 2014 among patients dependent on hemodialysis. Eligible cases were matched on index date with ten controls. We identified PPI and histamine-2 receptor antagonist use from Medicare Part D claims covering 3 years before the index date and stratified according to proportion of days covered by filled prescriptions. Using logistic regression with multiple imputation for missing data, we estimated unadjusted and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs).

Results: We studied 4551 cases and 45,510 controls. Patients were older, more likely to be female and white, and had shorter dialysis vintage; fewer were obese. A larger proportion of patients had any prior PPI (70% versus 63%) or histamine-2 receptor antagonist (25% versus 23%) use. Use of PPI was associated with higher risk of hip fracture (adjusted OR, 1.19; 95% CI, 1.11 to 1.28). This association remained within subgroups of low, moderate, and high PPI use, yielding adjusted ORs of 1.16 (95% CI, 1.06 to 1.27), 1.21 (95% CI, 1.11 to 1.31), and 1.19 (95% CI, 1.08 to 1.31), respectively.

Conclusions: Among patients with ESKD on hemodialysis, PPIs and not histamine-2 receptor antagonists were associated with hip fracture events.

Keywords: Epidemiology and outcomes; Hip Fractures; Histamine; Histamine H2 Antagonists; Kidney Failure, Chronic; Logistic Models; Medicare Part D; Odds Ratio; Proton Pump Inhibitors; USRDS; case-control; drug safety; end-stage renal disease; obesity; renal dialysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cross-Sectional Studies
  • Female
  • Hip Fractures / epidemiology
  • Hip Fractures / etiology*
  • Histamine H2 Antagonists / adverse effects*
  • Humans
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / therapy*
  • Male
  • Middle Aged
  • Proton Pump Inhibitors / adverse effects*
  • Renal Dialysis*
  • Retrospective Studies
  • Risk Assessment


  • Histamine H2 Antagonists
  • Proton Pump Inhibitors