title: Risk of severe upper gastrointestinal complications among oral bisphosphonate users.
abstract: BACKGROUND
  Oral bisphosphonates (BPs) are the primary agents for the treatment of osteoporosis. Although BPs are generally well tolerated, serious gastrointestinal adverse events have been observed.
  
  
  OBJECTIVE
  To assess the risk of severe upper gastrointestinal complications (UGIC) among BP users by means of a large study based on a network of Italian healthcare utilization databases.
  
  
  METHODS
  A nested case-control study was carried out by including 110,220 patients aged 45 years or older who, from 2003 until 2005, were treated with oral BPs. Cases were the 862 patients who experienced the outcome (hospitalization for UGIC) until 2007. Up to 20 controls were randomly selected for each case. Conditional logistic regression model was used to estimate odds ratio (OR) associated with current use of BPs after adjusting for several covariates. A set of sensitivity analyses was performed in order to account for sources of systematic uncertainty.
  
  
  RESULTS
  The adjusted OR for current use of BPs with respect to past use was 0.94 (95% CI 0.81 to 1.08). There was no evidence that this risk changed either with BP type and regimen, or concurrent use of other drugs or previous hospitalizations.
  
  
  CONCLUSIONS
  No evidence was found that current use of BPs increases the risk of severe upper gastrointestinal complications compared to past use.
authors.affiliation: Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Ghirardi
authors.affiliation: Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Scotti
authors.affiliation: Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Zambon
authors.affiliation: Department of Informatics, Systems and Communications, University of Milano-Bicocca, Milan, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Della Vedova
authors.affiliation: Operative Unit of Epidemiology, Local Health Unit of Monza, Monza-Brianza, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Cavalieri D'oro
authors.affiliation: Department of Epidemiology, Regional Agency for Healthcare Services of Tuscany, Florence, Italy ; Department of Preclinical and Clinical Pharmacology, University of Florence, Florence Italy ; Centre for Clinical Epidemiology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
authors.forename: Francesco
authors.initials: F
authors.lastname: Lapi
authors.affiliation: Department of Epidemiology, Regional Agency for Healthcare Services of Tuscany, Florence, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cipriani
authors.affiliation: Department of Medicine and Pharmacology, University of Messina, Messina, Italy.
authors.forename: Achille P
authors.initials: AP
authors.lastname: Caputi
authors.affiliation: Regional Centre for Drug Evaluation and Information (CREVIF), Department of Pharmacology, University of Bologna, Bologna, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Vaccheri
authors.affiliation: Department of Public Health and Microbiology, University of Turin, Turin, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Gregori
authors.affiliation: Center of Epidemiology, Biostatistics, and Medical Information Technology, Polytechnic University of Marche, Ancona, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Gesuita
authors.affiliation: Department of Experimental Medicine and Pathology, University "La Sapienza", Rome, Italy.
authors.forename: Annarita
authors.initials: A
authors.lastname: Vestri
authors.affiliation: Department of Medicine and Aging, University "G. d'Annunzio", Chieti-Pescara, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Staniscia
authors.affiliation: Department of Epidemiology, Regional Agency for Healthcare Services of Tuscany, Florence, Italy.
authors.forename: Giampiero
authors.initials: G
authors.lastname: Mazzaglia
authors.affiliation: Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Corrao
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D004164:Diphosphonates / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010024:Osteoporosis / Q000188:drug therapy
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates