title: Adverse effects of proton pump inhibitor drugs: clues and conclusions.
abstract: OBJECTIVE
  To review evidence relating to the strength of associations that have appeared in largely observational studies, between high-dose or long-term use of proton pump inhibitor drugs and certain possibly attributable side-effects, which emerge from studies confounded by other variables. In retrospective studies not designed to assess safety, evidence of causality is generally lacking.
  
  
  RESULTS
  The associations of fractures of hip, wrist, forearm and other sites appear weak and only slightly higher than the risks in control populations matched for age. They may increase with drug exposure, but probably do so only in individuals in whom other risk factors are also operational (smoking, alcohol, poor nutrition, steroids, etc.). The risks of Clostridium difficile colitis, other enteric infections, small bowel bacterial overgrowth and possibly spontaneous bacterial peritonitis also appear increased. Impaired gastric secretion may adversely affect the absorption of various nutrients, but their clinical impact is ill defined. Potentially more important are the consequences of hypergastrinemia, including rebound hypersecretion of acid, and possible development of various cancers, including carcinoid tumors. Effects of other drugs, including clopidogrel, on metabolism are reviewed, but clouded by uncertainties.
  
  
  CONCLUSIONS
  The safety of long-term PPI administration needs serious prospective study.
authors.affiliation: Division of Gastroenterology and Hepatology, Raymond G. Murphy VA Medical Center, University of New Mexico School of Medicine, Albuquerque, New Mexico 87108, USA. denis.mccarthy2@va.gov
authors.forename: Denis M
authors.initials: DM
authors.lastname: McCarthy
mesh_terms: D002276:Carcinoid Tumor / Q000453:epidemiology*; D016360:Clostridioides difficile; D003015:Clostridium Infections / Q000453:epidemiology; D003092:Colitis / Q000382:microbiology*; D004347:Drug Interactions; D050723:Fractures, Bone / Q000453:epidemiology; D005744:Gastric Acid / Q000378:metabolism*; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D008286:Malabsorption Syndromes / Q000453:epidemiology; D010538:Peritonitis; D054328:Proton Pump Inhibitors / Q000009:adverse effects*; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000453:epidemiology*
chemical_list: D054328:Proton Pump Inhibitors