Osteoporosis International

, Volume 27, Issue 6, pp 2117–2126 | Cite as

Gastroesophageal reflux disease with proton pump inhibitor use is associated with an increased risk of osteoporosis: a nationwide population-based analysis

  • C.-H. Chen
  • C.-L. Lin
  • C.-H. KaoEmail author
Original Article



Gastroesophageal reflux disease (GERD) with proton pump inhibitor (PPI) use is associated with an increased risk of osteoporosis. The risk of hip fracture is not increased in GERD patients with PPI use.


The relationship between GERD with PPI treatment and the risk of osteoporosis is unclear. We aimed to determine the risk of developing osteoporosis in patients diagnosed with GERD.


Patients diagnosed with GERD and received PPI treatment between 2000 and 2010 were identified from the Longitudinal Health Insurance Database as the study cohort (n = 10,620), which was frequency matched with the comparison cohort (n = 20,738) sampled from the general population according to age, sex, index year, and comorbidities. Both cohorts were followed until the end of 2011. The risk of osteoporosis was evaluated in both groups by using Cox proportional hazards regression models.


The GERD patients with PPI treatment had a greater incidence (31.4 vs 20.7 per 1000 person-year; crude hazard ratio [cHR] 1.51; 95 % confidence interval [CI] 1.40–1.63) and a higher risk (adjusted HR [aHR] 1.50; 95 % CI 1.39–1.62) of osteoporosis than that of the comparison cohort. However, the overall incidence of hip fracture was not different between the GERD with PPI use and the control cohorts (aHR 0.79; 95 % CI 0.53–1.18).


GERD with PPI use is associated with an increased risk of osteoporosis. The findings of our study do not support an increased risk of hip fracture in GERD patients treated with a PPI.


Gastroesophageal reflux disease (GERD) Hip fracture Osteoporosis Proton pump inhibitor (PPI) 



Gastroesophageal reflux disease


Proton pump inhibitor


Adjusted hazard ratio


Confidence interval


National Health Insurance Research Database


Longitudinal Health Insurance Database 2000


National Health Insurance


International Classification of Diseases, Ninth Revision, Clinical Modification


Bureau of National Health Insurance


Gamma-aminobutyric acid



This study is supported in part by Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW105-TDU-B-212-133019), China Medical University Hospital, Academia Sinica Taiwan Biobank Stroke Biosignature Project (BM10501010037), NRPB Stroke Clinical Trial Consortium (MOST 104-2325-B-039 -005), Tseng-Lien Lin Foundation, Taichung, Taiwan, Taiwan Brain Disease Foundation, Taipei, Taiwan, and Katsuzo and Kiyo Aoshima Memorial Funds, Japan; and CMU under the Aim for Top University Plan of the Ministry of Education, Taiwan.

Compliance with ethical standards

The NHIRD encrypts patient personal information to protect privacy and provides researchers with anonymous identification numbers associated with relevant claims information, including sex, date of birth, medical services received, and prescriptions. Therefore, patient consent is not required to access the NHIRD. This study was approved to fulfill the condition for exemption by the Institutional Review Board (IRB) of China Medical University (CMUH-104-REC2-115). The IRB also specifically waived the consent requirement.

Conflicts of interest



The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.


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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2016

Authors and Affiliations

  1. 1.Digestive Disease CenterShow-Chwan Memorial HospitalChanghuaTaiwan
  2. 2.Department of Food Science and TechnologyHungkuang UniversityTaichungTaiwan
  3. 3.Meiho University of TechnologyPingtungTaiwan
  4. 4.Management Office for Health DataChina Medical University HospitalTaichungTaiwan
  5. 5.College of MedicineChina Medical UniversityTaichungTaiwan
  6. 6.Graduate Institute of Clinical Medical Science, School of Medicine, College of MedicineChina Medical UniversityTaichungTaiwan
  7. 7.Department of Nuclear Medicine and PET CenterChina Medical University HospitalTaichungTaiwan

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