Proton pump inhibitors and fracture risk. The HUNT study, Norway

  • M. HoffEmail author
  • E. Skovlund
  • S. Skurtveit
  • H.E. Meyer
  • A. Langhammer
  • A.J. Søgaard
  • U. Syversen
  • S. Forsmo
  • B. Abrahamsen
  • B. Schei
Original Article



Proton pump inhibitors (PPIs) have been linked to increased risk of fracture; the data have, however, been diverging. We did not find any increased risk of fractures among users of PPIs in a Norwegian population of 15,017 women and 13,241 men aged 50–85 years with detailed information about lifestyle and comorbidity.


Proton pump inhibitors (PPIs) are widely prescribed and have been linked to increased risk of fracture.


We used data from the Nord-Trøndelag Health Study (HUNT3), The Fracture registry in Nord-Trøndelag, and the Norwegian Prescription Database, including 15,017 women and 13,241 men aged 50–85 years. The study population was followed from the date of participating in HUNT3 (2006–2008) until the date of first fracture (forearm or hip), death, or end of study (31 December 2012). The Cox proportional hazards model with time-dependent exposure to PPIs was applied, and each individual was considered as unexposed until the first prescriptions was filled. To be included, the prescription of PPIs should minimum be equivalent to 90 defined daily doses (DDD) in the period. Individuals were defined as exposed until 6 months after end of drug supply.


The proportion of women and men using PPIs was 17.9% and 15.5%, respectively. During a median of 5.2 years follow-up, 266 women and 134 men had a first hip fracture and 662 women and 127 men, a first forearm fracture. The combined rate/1000 patient-years for forearm and hip fractures in women was 49.2 for users of PPIs compared with 64.1 among non-users; for men 18.6 and 19.8, respectively. The hazard ratios with 95% confidence interval for the first forearm or hip fracture among users of PPIs in the age-adjusted analysis were 0.82 (0.67–1.01) for women and 1.05 (0.72–1.52) for men. Adjusting for age, use of anti-osteoporotic drugs, and FRAX, the HR declined to 0.80 (0.65–0.98) in women and 1.00 (0.69–1.45) in men.


Use of PPIs was not associated with an increased risk of fractures.


Fracture General population studies HUNT Osteoporosis Proton pump inhibitors 



The Nord-Trøndelag Health Study (The HUNT Study) is a collaboration between HUNT Research Centre (Faculty of Medicine, Norwegian University of Science and Technology

NTNU), Nord-Trøndelag County Council, Central Norway Health Authority, and the Norwegian Institute of Public Health.

Funding information

MH received a post-doctoral fellowship grant from the Liaison Committee between the Central Norway Regional Health Authority (RHA) and the Norwegian University of Science and Technology (NTNU).

BA has institutional research contracts with UCB and Novartis with funds paid to the institutions.

US has received research grants from or served as a Principal Investigator in studies conducted by Amgen, Eli Lilly, Novartis, Merck, and Wyeth pharmaceuticals.

Compliance with ethical standards

Conflicts of interest

MH, SS, HM, AD, AJS, AL, ES, SF, and BS have no disclosures.

Supplementary material

198_2019_5206_MOESM1_ESM.docx (22 kb)
ESM 1 (DOCX 22 kb)


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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2019

Authors and Affiliations

  1. 1.Department of Public Health and NursingNorwegian University of Science and TechnologyTrondheimNorway
  2. 2.Department of RheumatologySt Olavs HospitalTrondheimNorway
  3. 3.Norwegian Institute of Public HealthOsloNorway
  4. 4.Department of Community Medicine and Global HealthUniversity of OsloOsloNorway
  5. 5.Department of EndocrinologySt. Olavs HospitalTrondheimNorway
  6. 6.Department of Clinical and and Molecular MedicineNTNUTrondheimNorway
  7. 7.Norwegian Centre for Addiction ResearchUniversity of OsloOsloNorway
  8. 8.Department of MedicineHolbæk HospitalHolbækDenmark
  9. 9.Odense Patient Data Explorative Network, Institute of Clinical ResearchUniversity of Southern DenmarkOdenseDenmark
  10. 10.Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal SciencesUniversity of OxfordOxfordUK
  11. 11.Department of GynecologySt Olavs HospitalTrondheimNorway

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