N E Morden1, J C Munson, J Smith, T A Mackenzie, S K Liu, A N A Tosteson. 1. The Dartmouth Institute for Health Policy & Clinical Practice, Geisel School of Medicine at Dartmouth, 35 Centerra Parkway, Room 3088, Lebanon, NH, 03766, USA, nancy.e.morden@dartmouth.edu.
Abstract
SUMMARY: We evaluated the association between bisphosphonate use and (1) upper gastrointestinal cancer, (2) upper endoscopy, (3) incident Barrett's esophagus, and (4) prescription antacid initiation among Medicare beneficiaries. We found no bisphosphonate-cancer association and negative bisphosphonate-Barrett's association. INTRODUCTION: Bisphosphonates can irritate the esophagus; a cancer association has been suggested. Widespread bisphosphonates use compels continued investigation of upper gastrointestinal toxicity. METHODS: Using a 40% Medicare random sample denominator, inpatient, outpatient (2003-2011), and prescription (2006-2011) claims, we studied patients age 68 and older with osteoporosis and/or oral bisphosphonate use. Inverse propensity weighting estimated marginal structural models for the effect of bisphosphonate intensity (pills per month) and cumulative bisphosphonate pills received on upper gastrointestinal cancer risk. Secondary analyses of sub-cohorts without past bisphosphonates or upper endoscopy assessed bisphosphonate initiation and risk of (1) upper endoscopy, (2) incident Barrett's esophagus, and (3) prescription antacid initiation. RESULTS: The cohort included 1.64 million beneficiaries: 87.9% women, mean age, 76.8 (standard deviation (SD) 9.3); mean follow-up, 39.6 months; 38.1% received oral bisphosphonates. Cumulative bisphosphonate receipt, among users, ranged from 4 to 252 pills (5th to 95th percentile). We identified 2,308 upper gastrointestinal cancers (0.43/1000 person years). We found no association between cumulative bisphosphonate pills and cancer, odds ratio (OR) for each additional pill 1.00 (95% confidence interval (CI) 1.00, 1.00). In sub-cohorts, compared to none, lowest cumulative bisphosphonate use (one to nine pills) was associated with higher risk of endoscopy (OR 1.11, 95% CI 1.08-1.14) and antacid initiation (OR 1.13, 95% CI 1.10-1.16); higher intensity conferred no increased risk. Higher intensity and higher cumulative bisphosphonate category were associated with lower Barrett's risk. CONCLUSIONS: We found no bisphosphonate-cancer association and negative bisphosphonate-Barrett's association. Bisphosphonate initiation appears to identify patients susceptible to early irritating effects; clinicians might offer alternatives and delay endoscopy or antacids.
SUMMARY: We evaluated the association between bisphosphonate use and (1) upper gastrointestinal cancer, (2) upper endoscopy, (3) incident Barrett's esophagus, and (4) prescription antacid initiation among Medicare beneficiaries. We found no bisphosphonate-cancer association and negative bisphosphonate-Barrett's association. INTRODUCTION:Bisphosphonates can irritate the esophagus; a cancer association has been suggested. Widespread bisphosphonates use compels continued investigation of upper gastrointestinal toxicity. METHODS: Using a 40% Medicare random sample denominator, inpatient, outpatient (2003-2011), and prescription (2006-2011) claims, we studied patients age 68 and older with osteoporosis and/or oral bisphosphonate use. Inverse propensity weighting estimated marginal structural models for the effect of bisphosphonate intensity (pills per month) and cumulative bisphosphonate pills received on upper gastrointestinal cancer risk. Secondary analyses of sub-cohorts without past bisphosphonates or upper endoscopy assessed bisphosphonate initiation and risk of (1) upper endoscopy, (2) incident Barrett's esophagus, and (3) prescription antacid initiation. RESULTS: The cohort included 1.64 million beneficiaries: 87.9% women, mean age, 76.8 (standard deviation (SD) 9.3); mean follow-up, 39.6 months; 38.1% received oral bisphosphonates. Cumulative bisphosphonate receipt, among users, ranged from 4 to 252 pills (5th to 95th percentile). We identified 2,308 upper gastrointestinal cancers (0.43/1000 person years). We found no association between cumulative bisphosphonate pills and cancer, odds ratio (OR) for each additional pill 1.00 (95% confidence interval (CI) 1.00, 1.00). In sub-cohorts, compared to none, lowest cumulative bisphosphonate use (one to nine pills) was associated with higher risk of endoscopy (OR 1.11, 95% CI 1.08-1.14) and antacid initiation (OR 1.13, 95% CI 1.10-1.16); higher intensity conferred no increased risk. Higher intensity and higher cumulative bisphosphonate category were associated with lower Barrett's risk. CONCLUSIONS: We found no bisphosphonate-cancer association and negative bisphosphonate-Barrett's association. Bisphosphonate initiation appears to identify patients susceptible to early irritating effects; clinicians might offer alternatives and delay endoscopy or antacids.