Oral Bisphosphonates and the Risk of Barrett's Esophagus
Oral Bisphosphonates and the Risk of Barrett's Esophagus
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.
Bisphosphonates are selective inhibitors of osteoclast-mediated bone resorption that are used for the treatment and prevention of osteoporosis. The use of oral bisphosphonates has increased dramatically in recent years, despite its association with adverse gastrointestinal effects, including an increased risk of esophagitis, esophageal erosions, and esophageal ulcers.
Barrett's esophagus (BE) is a known premalignant precursor lesion in most cases of esophageal adenocarcinoma and is a relatively common problem, thought to affect 1–2% of the general population. The risk of esophageal adenocarcinoma in patients with BE is 30–125 times greater than the general population. The US Food and Drug Administration (FDA) reported on several cases of esophageal adenocarcinoma in bisphosphonate users. Some of these patients also carried a diagnosis of BE. The author of that FDA report cautioned physicians to avoid prescribing oral bisphosphonates to patients with BE. However, recent population-based studies examining the association between bisphosphonate use and esophageal adenocarcinoma have arrived at conflicting results. Moreover, to assess the safety of oral bisphosphonates, it is important to examine its association with BE. To our knowledge, there are no published studies on this subject.
We conducted a case–control study to examine BE risk factors in a large population of US veterans. Here we report the association between the risk of BE with oral bisphosphonate use, ascertained by pharmacy records.
Abstract and Introduction
Abstract
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.
Introduction
Bisphosphonates are selective inhibitors of osteoclast-mediated bone resorption that are used for the treatment and prevention of osteoporosis. The use of oral bisphosphonates has increased dramatically in recent years, despite its association with adverse gastrointestinal effects, including an increased risk of esophagitis, esophageal erosions, and esophageal ulcers.
Barrett's esophagus (BE) is a known premalignant precursor lesion in most cases of esophageal adenocarcinoma and is a relatively common problem, thought to affect 1–2% of the general population. The risk of esophageal adenocarcinoma in patients with BE is 30–125 times greater than the general population. The US Food and Drug Administration (FDA) reported on several cases of esophageal adenocarcinoma in bisphosphonate users. Some of these patients also carried a diagnosis of BE. The author of that FDA report cautioned physicians to avoid prescribing oral bisphosphonates to patients with BE. However, recent population-based studies examining the association between bisphosphonate use and esophageal adenocarcinoma have arrived at conflicting results. Moreover, to assess the safety of oral bisphosphonates, it is important to examine its association with BE. To our knowledge, there are no published studies on this subject.
We conducted a case–control study to examine BE risk factors in a large population of US veterans. Here we report the association between the risk of BE with oral bisphosphonate use, ascertained by pharmacy records.
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