Oral Bisphosphonates and the Risk of Barrett's Esophagus: Case-Control Analysis of US Veterans

ArticleinThe American Journal of Gastroenterology 108(10) · July 2013with7 Reads
DOI: 10.1038/ajg.2013.222 · Source: PubMed
Objectives: This study examined Barrett's esophagus (BE) risk factors in veterans to determine the association between risk of BE and use of oral bisphosphonates. Methods: We conducted a case-control study among eligible patients scheduled for an elective esophagogastroduodenoscopy (EGD) and a sample of patients eligible for screening colonoscopy recruited from primary care clinics from a single VA Medical Center. Cases with definitive BE were compared with controls; all underwent study EGD. Use of oral bisphosphonates was ascertained by reviewing filled prescriptions in electronic pharmacy records. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs), using multivariate logistic regression modeling while adjusting for sex, age, race, proton-pump inhibitor use, hiatal hernia, waist-to-hip ratio, Helicobacter pylori infection, and gastroesophageal reflux disorder (GERD) symptoms. Results: There were 285 BE cases, 1,122 endoscopy controls, and 496 primary care controls. Alendronate and risedronate were the only oral bisphosphonates prescribed. The proportion of BE cases with filled prescription of oral bisphosphonates (4.6%) was greater than in endoscopy controls (1.6%) or primary care controls (2.9%). In the adjusted analysis, oral bisphosphonate use was significantly associated with BE risk (OR=2.33; 95% CI: 1.11-4.88) compared with the combined control groups. This association remained significant when BE cases were compared with endoscopy controls only (OR=2.74; 95% CI: 1.28-5.87) but was attenuated when compared with primary care controls only (OR=2.60; 95% CI: 0.99-6.84). The association was observed in patients with GERD symptoms (OR=3.29; 95% CI: 1.36-7.97) but not in those without GERD symptoms. Conclusion: Oral bisphosphonate use may increase the risk for BE, especially among patients with GERD.
    • "In addition, two other studies identified an increased association between BE and anti-reflux medication [27, 63]. Lin et al. [29] identified that oral bisphosphonates increase the risk, but this was potentially due to non-compliance with medication administration, rather than a direct relationship. Their study identified that people may not have been remaining upright following administration as instructed, suggesting that there may be injury to the esophagus from the bisphosphonates, causing BE. "
    [Show abstract] [Hide abstract] ABSTRACT: Introduction: Cancer of the esophagus is a highly lethal disease with many patients presenting with metastatic spread of their tumor at diagnosis; a consequence of this late presentation is the 5-year survival rate of <20 %. Barrett's esophagus (BE), a premalignant condition of the distal esophagus, is the main risk factor for adenocarcinoma of the esophagus. The development of a risk prediction tool that could assist healthcare professionals in identifying people at increased risk of developing BE would be advantageous. Understanding the factors that influence the risk of developing BE is the first stage of developing a risk prediction tool. Methods: A scoping review was undertaken to address the following question 'what factors influence the risk of developing Barrett's esophagus?' Forty-six articles were included in this review. Results: The majority of articles reviewed were case-control or cohort studies. Samples sizes ranged from 68 to 84,606. Risk factors reported to be statistically significant were divided into three categories: demographic, lifestyle and clinical factors. Strongest risk factors identified include: male gender, increasing age, white race, smoking, obesity and gastro-esophageal reflux disease symptoms, while some aspects of a person's diet appear to act as a protective measure. Conclusion: Risk factors for BE are complex and need to be considered by healthcare professionals when identifying patients that could benefit from endoscopic eradication. These results provide a stepping stone for the future development of a risk prediction model.
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  • [Show abstract] [Hide abstract] ABSTRACT: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been suggested to protect against esophageal adenocarcinoma (EAC). This study examined the effect of NSAIDs on the risk of developing Barett's esophagus (BE), the precursor lesion to EAC. We conducted a case-control study among eligible patients scheduled for either elective esophagogastroduodenoscopy (EGD) or recruited from primary care clinics to undergo a study EGD. We compared 323 patients with BE (296 nondysplastic and 27 dysplastic) with 2 separate control groups: 1347 patients from the elective EGD group ("endoscopy controls") and 502 patients from the primary care group ("primary care controls") with no endoscopic or histopathologic BE. Use of aspirin products and 23 nonaspirin NSAIDs was ascertained from detailed, self-reported questionnaires. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic-regression models. There were no significant differences in self-reported NSAID use between all BE cases and all controls (58.2% vs. 54.6%, P=0.33); this was seen for aspirin products (43.0% vs. 37.4%, P=0.08) and nonaspirin NSAIDs (7.7% vs. 8.9%, P=0.46). These findings persisted in the multivariable model for any NSAIDs (adjusted OR 0.89; 95% CI 0.75-1.28), aspirin (adjusted OR 1.16; 95% CI 0.90-1.51), and nonaspirin NSAIDs (adjusted OR 0.88; 95% CI 0.55-1.39). Use of a combination of aspirin and nonaspirin NSAIDs was reported in 7.4% cases and 8.3% controls, and a non-significant inverse association with BE was seen (adjusted OR 0.70; 95% CI 0.44-1.11). There was no significant association between BE and daily NSAID use (adjusted OR 1.03; 95% CI 0.78-1.37). Similar findings were observed for comparisons involving nondysplastic or dysplastic BE cases, and endoscopy or primary care control groups separately or combined. The use of NSAIDs was not associated with a reduced risk of BE. It is likely that the protective mechanism of NSAIDs on EAC occurs subsequent to the development of BE.
    Article · Apr 2014
  • [Show abstract] [Hide abstract] ABSTRACT: The highest incidence and prevalence of Barrett's oesophagus is in western countries. Risk factors include smoking, obesity, gastro-oesophageal reflux disease and hiatus hernia, increasing age and use of oral bisphosphonates. This article discusses the significance of these findings.
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