title: Oral Bisphosphonates and Upper Gastrointestinal Cancer Risks in Asians with Osteoporosis: A Nested Case-Control Study Using National Retrospective Cohort Sample Data from Korea.
abstract: BACKGROUND
  Bisphosphonate can irritate the gastrointestinal mucosa and increase the risk of esophageal or gastric cancer. The relatively high prevalence of upper gastrointestinal cancers and the widespread use of bisphosphonate in Korea call for further investigation. We conducted a case-control study to evaluate the risk of esophageal or gastric cancer after exposure to oral bisphosphonates in Korean patients with osteoporosis.
  
  
  METHODS
  We used the National Health Insurance Service-National Sample Cohort database of Korea from 2002 to 2013. Among osteoporotic patients (>40 years), cases were defined as incident diagnosis of esophageal or gastric cancer between 2006 and 2013. For each case, four controls were matched for age, sex, and income level by type of insurance. We categorized bisphosphonate use as non-user, recent user, past user, and past and recent user, depending on prescription in two periods (1 to 2 years and 2 to 4 years prior to the index date). We also assessed the duration of bisphosphonate use by measuring cumulative duration of exposure (CDE). To examine the association between oral bisphosphonates and esophageal or gastric cancer, we estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) using conditional logistic regression analysis, adjusting for concomitant diseases.
  
  
  RESULTS
  A total of 1,708 cases and 6,832 controls were identified. The aORs (95% CIs) of recent, past, and continuous bisphosphonate use compared to non-users were 1.18 (0.93-1.51), 1.04 (0.83-1.29), and 1.25 (0.95-1.58)), respectively. In addition, no significant association was observed by CDE, even when different outcome definitions were applied.
  
  
  CONCLUSIONS
  This study did not prove an increased risk of esophageal or gastric cancer risk associated with bisphosphonate use, with respect to both risk windows and duration of exposure, in an Asian population-based, real-world setting.
authors.affiliation: Office of Pharmacoepidemiology, Korea Institute of Drug Safety and Risk Management, Anyang, Gyeonggi-do, Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Jung
authors.affiliation: Graduate School of Clinical Pharmacy, CHA University, Gyeonggi-do, Korea.
authors.forename: Hyun Soon
authors.initials: HS
authors.lastname: Sohn
authors.affiliation: Korea Institute for Health and Social Affairs, Sejong, Korea.
authors.forename: Eun-Ja
authors.initials: EJ
authors.lastname: Park
authors.affiliation: College of Pharmacy, Pusan National University, Busan, Korea.
authors.forename: Hae Sun
authors.initials: HS
authors.lastname: Suh
authors.affiliation: College of Natural Science, Kyungpook National University, Daegu, Korea.
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Park
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Korea.
authors.forename: Jin-Won
authors.initials: JW
authors.lastname: Kwon
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D016208:Databases, Factual; D004164:Diphosphonates / Q000009:adverse effects*; D004938:Esophageal Neoplasms / Q000453:epidemiology* / Q000208:ethnology / Q000209:etiology / Q000473:pathology; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D005770:Gastrointestinal Neoplasms / Q000453:epidemiology* / Q000208:ethnology / Q000209:etiology / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009313:National Health Programs / Q000706:statistics & numerical data; D016017:Odds Ratio; D010024:Osteoporosis / Q000188:drug therapy / Q000453:epidemiology* / Q000208:ethnology / Q000473:pathology; D056910:Republic of Korea / Q000453:epidemiology; D012737:Sex Factors; D041742:Upper Gastrointestinal Tract / Q000187:drug effects / Q000473:pathology
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates