Osteoporosis International

, Volume 26, Issue 10, pp 2501–2507 | Cite as

Use of proton pump inhibitors is associated with fractures in young adults: a population-based study

  • D. E. FreedbergEmail author
  • K. Haynes
  • M. R. Denburg
  • B. S. Zemel
  • M. B. Leonard
  • J. A. Abrams
  • Y.-X. Yang
Original Article



Proton pump inhibitors (PPIs) are associated with risk for fracture in osteoporotic adults. In this population-based study, we found a significant association between PPIs and fracture in young adults, with evidence of a dose–response effect. Young adults who use PPIs should be cautioned regarding risk for fracture.


Proton pump inhibitors (PPIs) are associated with fracture in adults with osteoporosis. Because PPI therapy may interfere with bone accrual and attainment of peak bone mineral density, we studied the association between use of PPIs and fracture in children and young adults.


We conducted a population-based, case–control study nested within records from general medical practices from 1994 to 2013. Participants were 4–29 years old with ≥1 year of follow-up who lacked chronic conditions associated with use of long-term acid suppression. Cases of fracture were defined as the first incident fracture at any site. Using incidence density sampling, cases were matched with up to five controls by age, sex, medical practice, and start of follow-up. PPI exposure was defined as 180 or more cumulative doses of PPIs. Conditional logistic regression was used to estimate the odds ratio and confidence interval for use of PPIs and fracture.


We identified 124,799 cases and 605,643 controls. The adjusted odds ratio for the risk of fracture associated with PPI exposure was 1.13 (95 % CI 0.92 to 1.39) among children aged <18 years old and 1.39 (95 % CI 1.26 to 1.53) among young adults aged 18–29 years old. In young adults but not children, we observed a dose–response effect with increased total exposure to PPIs (p for trend <0.001).


PPI use was associated with fracture in young adults, but overall evidence did not support a PPI–fracture relationship in children. Young adults who use PPIs should be cautioned regarding potentially increased risk for fracture, even if they lack traditional fracture risk factors.


Acid suppression medications Bone mineral density Fracture Histamine-2 receptor antagonists Osteoporosis Outcomes research Pediatrics Pharmacoepidemiology Proton pump inhibitors 


Conflicts of interest



Daniel Freedberg was funded by the National Center for Advancing Translational Sciences (NIH KL2TR000081); Michelle Denburg was funded by the NIH (K23 DK093556) and a Nephcure Foundation–American Society of Nephrology Research Grant; Mary Leonard was funded by the NIH (K24DK076808). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or other organizations.

Supplementary material

198_2015_3168_MOESM1_ESM.docx (28 kb)
Supplementary Table 1 Fracture type within the study, by age and sex. (DOCX 27 kb)
198_2015_3168_MOESM2_ESM.docx (27 kb)
Supplementary Table 2 Fracture type within the study, by age and PPI exposure. (DOCX 26 kb)
198_2015_3168_MOESM3_ESM.docx (24 kb)
Supplementary Table 3 Conditional logistic regression model for the relationship between proton pump inhibitors and fracture, by age. (DOCX 23 kb)
198_2015_3168_MOESM4_ESM.docx (24 kb)
Supplementary Table 4 Conditional logistic regression model for the relationship between acid suppression and fracture, by age. (DOCX 23 kb)


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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2015

Authors and Affiliations

  • D. E. Freedberg
    • 1
    Email author
  • K. Haynes
    • 2
  • M. R. Denburg
    • 3
  • B. S. Zemel
    • 4
  • M. B. Leonard
    • 5
  • J. A. Abrams
    • 1
  • Y.-X. Yang
    • 2
    • 6
  1. 1.Division of Digestive and Liver DiseasesColumbia University Medical CenterNew YorkUSA
  2. 2.Center for Clinical Epidemiology and Biostatistics, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Division of NephrologyThe Children’s Hospital of PhiladelphiaPhiladelphiaUSA
  4. 4.Department of Pediatrics, The Children’s Hospital of Philadelphia, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  5. 5.Departments of Medicine and PediatricsStanford University School of MedicineStanfordUSA
  6. 6.Division of Gastroenterology, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA

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