title: Alendronate, a bisphosphonate, increased upper and lower gastrointestinal bleeding: risk factor analysis from a nationwide population-based study.
abstract: Patients receiving alendronate for osteoporosis carry a significantly higher risk of developing upper gastrointestinal bleeding (GIB) and lower GIB (hazard ratio 1.32 and 1.84, respectively) after adjusting for potential confounding factors such as age, gender, co-morbidity, and some medications. The risk factors associated with GIB were further analyzed.
  
  
  BACKGROUND
  Patients receiving alendronate, a type of bisphosphonate, for osteoporosis have a higher risk of developing upper gastrointestinal bleeding (UGIB). Whether patients receiving alendronate also have a higher risk of lower gastrointestinal bleeding (LGIB) has not been studied. In this study, we investigated the association between GIB and alendronate use and to identify the possible risk factors of GIB among alendronate users.
  
  
  METHODS
  Using the National Health Insurance (NHI) Research Database of Taiwan, 3,000 alendronate users and 12,000 age-, sex-, and enrollment time-matched controls were extracted for analysis from a cohort data set of 1,000,000 randomly sampled subjects. Cox proportional hazard regression models were used to identify the risk factors for UGIB and LGIB in all enrollees and alendronate users after adjustments for age, gender, comorbidity (hypertension, diabetes mellitus, coronary heart disease, heart failure, chronic renal disease, chronic obstructive pulmonary disease, peptic ulcer, and cirrhosis), and medications (nonsteroidal anti-inflammatory drugs [NSAIDs], aspirin, steroids, clopidogrel, ticlopidine, warfarin, and selective serotonin reuptake inhibitors).
  
  
  RESULTS
  During a median of 1.30-year follow-up, patients receiving alendronate had significant higher risk of UGIB and LGIB after adjusting for age, gender, and potential confounding factors such as comorbidity and medications. Age, chronic renal disease, NSAID, and clopidogrel use may be independent risk factors for UGIB among alendronate users. Age, male gender, clopidogrel, and ticlopidine use may be independent risk factors for LGIB among alendronate users.
  
  
  CONCLUSIONS
  Patients receiving alendronates seemed to carry a higher risk for UGIB and LGIB, respectively, after adjustment for age, sex, underlying comorbidity, and certain medications.
authors.affiliation: Department of Medicine, School of Medicine, National Yang-Ming University, #155, Linong Street, Section 2, Taipei City, 11217, Taiwan.
authors.forename: Y-L
authors.initials: YL
authors.lastname: Peng
authors.forename: H-Y
authors.initials: HY
authors.lastname: Hu
authors.forename: J-C
authors.initials: JC
authors.lastname: Luo
authors.forename: M-C
authors.initials: MC
authors.lastname: Hou
authors.forename: H-C
authors.initials: HC
authors.lastname: Lin
authors.forename: F-Y
authors.initials: FY
authors.lastname: Lee
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000009:adverse effects* / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D001241:Aspirin / Q000009:adverse effects; D050071:Bone Density Conservation Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D015897:Comorbidity; D015986:Confounding Factors, Epidemiologic; D016208:Databases, Factual; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy / Q000453:epidemiology; D012307:Risk Factors; D012737:Sex Factors; D013624:Taiwan / Q000453:epidemiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D050071:Bone Density Conservation Agents; D001241:Aspirin; D019386:Alendronate