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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. Kao
Published 2016 · Medicine
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SummaryGastroesophageal 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.IntroductionThe 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.MethodsPatients 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.ResultsThe 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).ConclusionGERD 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.
This paper references
Gastro-oesophageal reflux disease
Albert J Bredenoord (2000)
Glucocorticoid-induced osteoporosis and osteonecrosis.
Robert S. Weinstein (2012)
Gastroesophageal reflux disease and the elderly.
Sami R. Achem (2014)
Activation of the inducible nitric oxide synthase pathway contributes to inflammation-induced osteoporosis by suppressing bone formation and causing osteoblast apoptosis
KJ Armour (2001)
Proton pump inhibitors and nitric oxide mechanisms in type 2 diabetes
Jonas T. C. Sertorio (2013)
The potential impact of new National Osteoporosis Foundation guidance on treatment patterns
B. Dawson-Hughes (2009)
The Montreal Definition and Classification of Gastroesophageal Reflux Disease: A Global Evidence-Based Consensus
N. Vakil (2006)
Osteoporosis and fractures in liver disease: relevance, pathogenesis and therapeutic implications.
Inaam A. Nakchbandi (2014)
Assessment of fracture risk
J. Kanis (2004)
New horizons in treatment of osteoporosis
O. Tabatabaei-Malazy (2017)
Osteoporosis: now and the future
Tilman D Rachner (2011)
International Population Reports, p 95/ 09–1
K Kinsella (2009)
Adverse effects of hyperlipidemia on bone regeneration and strength.
Flávia Q Pirih (2012)
Links between cardiovascular disease and osteoporosis in postmenopausal women: serum lipids or atherosclerosis per se?
Yu Zhao Bagger (2006)
Proton pump inhibitor use, hip fracture, and change in bone mineral density in postmenopausal women: results from the Women's Health Initiative.
S. Gray (2010)
Epidemiology of Gastroesophageal Reflux Disease in Asia: A Systematic Review
Hye-Kyung Jung (2011)
Prevalence, clinical spectrum and health care utilization of gastro-oesophageal reflux disease in a Chinese population: a population-based study.
Wai-Man Wong (2003)
Combination therapy of gamma-aminobutyric acid derivative promotes proton pump inhibitor based healing of reflux esophagitis in animal model.
P. J. Khinchi (2014)
Ethnicity, gender, and socioeconomic status as risk factors for esophagitis and Barrett's esophagus.
A. Ford (2005)
The Frequency and Severity of Gastrointestinal Symptoms in Patients with Early Parkinson’s Disease
Hye-Young Sung (2014)
Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals?
M. Giorgio (2007)
The clinical diagnosis of osteoporosis: a position statement from the National Bone Health Alliance Working Group
Ethel S. Siris (2014)
Correlates of bone mineral density in men of African ancestry: The Tobago Bone Health Study
Deanna D Hill (2007)
Effects of different proton pump inhibitors on cardiac contractility in isolated human failing myocardium.
Samuel Sossalla (2011)
Gastroesophageal reflux might cause esophagitis through a cytokine-mediated mechanism rather than caustic acid injury.
Rhonda F. Souza (2009)
Bone mineral density changes among women initiating proton pump inhibitors or H2 receptor antagonists: a SWAN cohort study.
Daniel H. Solomon (2015)
The effect of proton pump inhibitors on fracture risk: report from the Canadian Multicenter Osteoporosis Study
L-A. Fraser (2012)
Use of proton pump inhibitors and risk of osteoporosis-related fractures
L. Targownik (2008)
Changing prevalence of gastroesophageal reflux with changing time: longitudinal study in an Asian population.
S. L. Lim (2005)
GABAergic mechanisms in epilepsy.
D. M. Treiman (2001)
Epilepsy and bone health in adults
Alison M. Pack (2004)
Amout AJPM (2013) Gastrooesophageal reflux disease
AJ Bredenoord (1933)
CaMos Research Group (2013) The effect of proton pump inhibitors on fracture risk: report from the Canadian Multicenter Study
LA Fraser (2013)
Proton-pump inhibitor use is not associated with osteoporosis or accelerated bone mineral density loss. Gastroenterology
LE Targownik (2010)
Epidemiology of gastro-oesophageal reflux disease: a systematic review
J. Dent (2005)
Pathophysiology of osteoporosis: new mechanistic insights.
Laura Armas (2012)
Hyperparathyroidism Associated with Long-Term Proton Pump Inhibitors Independent of Concurrent Bisphosphonate Therapy in Elderly Adults.
Andrew M Hinson (2015)
Rapidly increasing rates of hip fracture in Beijing, China.
Wei-bo Xia (2012)
Proton Pump Inhibitors, Histamine H2 Receptor Antagonists, and Other Antacid Medications and the Risk of Fracture
P. Vestergaard (2006)
Activation of the inducible nitric oxide synthase pathway contributes to inflammation-induced osteoporosis by suppressing bone formation and causing osteoblast apoptosis.
K. Armour (2001)
The Relationship Among Hypertension, Antihypertensive Medications, and Osteoporosis: A Narrative Review
Katarina Ilić (2012)
C,Woodhall GL, Stanford IM (2014) GABAmediated changes in inter-hemispheric beta frequency activity in early-stage Parkinson’s disease
SD Hall (2014)
Pathophysiology of osteoporosis.
Robert Proulx Heaney (1996)
Gastroesophageal reflux in cirrhotic patients without esophageal varices.
J. Zhang (2011)
Prevalence, risk factors and impact of gastroesophageal reflux disease symptoms: A population-based study in South China
M. Chen (2005)
GABA-mediated changes in inter-hemispheric beta frequency activity in early-stage Parkinson’s disease
S. Hall (2014)
Relevance , pathogenesis and therapeutic implications
IA Nakchbandi (2014)
Proton-pump inhibitor use is not associated with osteoporosis or accelerated bone mineral density loss.
L. Targownik (2010)
Influence of age and sex on endoscopic findings of gastrooesophageal reflux disease: an endoscopy database study
Shyam Menon (2011)
Oxidative stress is more important than acid in the pathogenesis of reflux oesophagitis in rats
T. Oh (2001)
Long-term proton pump inhibitor therapy and risk of hip fracture.
Yu-Xiao Yang (2006)

This paper is referenced by
Lower Trabecular Bone Score is Associated With the Use of Proton Pump Inhibitors.
Young Ho Shin (2019)
Gastrointestinal manifestations of systemic sclerosis
Andrew B. Shreiner (2016)
Latest insights into the hot question of proton pump inhibitor safety - a narrative review.
V. Savarino (2020)
Higher dose but not low dose proton pump inhibitors are associated with increased risk of subsequent hip fractures after first hip fracture: A nationwide observational cohort study
W. Brozek (2019)
Comparative analysis of the risk of osteoporotic fractures with proton pump inhibitor use and histamine-2 receptor antagonist therapy in elderly women: A nationwide population-based nested case-control study.
J. Park (2020)
Proton Pump Inhibitors and Fracture Risk: A Review of Current Evidence and Mechanisms Involved
Benjamin Ka Seng Thong (2019)
The use of proton pump inhibitors is positively associated with osteoporosis in postmenopausal women in Germany
Louis Jacob (2016)
Association Between Cataract and Risk of Incident Atrial Fibrillation
Wei-Syun Hu (2017)
Chapter 13 - Gastrointestinal Involvement in Systemic Sclerosis
Andrew B. Shreiner (2017)
Effects of Osteopathic Visceral Treatment in Patients with Gastroesophageal Reflux: A Randomized Controlled Trial
Nuria Eguaras (2019)
Risk of gallstones in patients with obstructive sleep apnea: a nationwide observational cohort study
Chien-hua Chen (2018)
Proton pump inhibitor use and the risk of osteoporosis and fracture in stroke patients: a population-based cohort study
S. Lin (2017)
A safety review of proton pump inhibitors to treat acid-related digestive diseases
E. Savarino (2018)
Proton pump inhibitors therapy and risk of bone diseases: An update meta‐analysis
J. Liu (2019)
Proton-pump inhibitors: understanding the complications and risks
Peter Malfertheiner (2017)
An updated meta-analysis : the effect of proton pump inhibitor on risk of osteoporosis and fracture
Xiu-De Fan (2017)
Fractures in postmenopausal women. Background factors and fracture risk assessment.
L Moberg (2016)
Effect of acute pancreatitis on the risk of developing osteoporosis: A nationwide cohort study
S. Lin (2017)
Proton pump inhibitors and risk of hip fracture: a meta-analysis of observational studies
Tahmina Nasrin Poly (2018)
Relationship between long-term use of proton pump inhibitors and risk of gastric cancer: A systematic analysis.
Kailin Jiang (2019)
Adverse outcomes of long-term use of proton pump inhibitors: a systematic review and meta-analysis
M. M. Islam (2018)
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