title: Use of the oral platelet inhibitors dipyridamole and acetylsalicylic acid is associated with increased risk of fracture.
abstract: BACKGROUND
  Platelet inhibitors are widely used in the treatment and prevention of coronary artery disease. In addition to acetylsalicylic acid, two major groups of platelet inhibitors are used; phosphodiesterase inhibitors including dipyridamole, and thienopyridines (ticlopidine and clopidogrel). Clopidogrel is the most widely used, and in combination with acetylsalicylic acid it is the standard of care for acute coronary syndromes and percutaneous coronary interventions. However, the modes of action involve pathways that are involved in the metabolic activity in bone cells and pharmacologic modulation of these pathways may therefore have effects on bone.
  
  
  METHODS
  In the current study, we assessed the association between platelet inhibitor use and fracture incidence in a population-based epidemiological study performed within the Danish population consisting of approximately 5.3 million individuals, where all patients sustaining a fracture during the year of 2000 were included (124,655 cases). The hypotheses were to investigate if use of thienopyridines or phosphodiesterase inhibitors were associated with increased risk of fractures after adjustment for potential confounders.
  
  
  RESULTS
  We found that treatment with dipyridamole is associated with increased overall fracture risk, but not to the risk of osteoporotic fractures. In contrast, low-dose acetylsalicylic acid is associated to increased risk of overall fractures and fractures of the hip. Finally, in the current study clopidogrel is not associated with increased fracture risk.
  
  
  CONCLUSIONS
  Use of some oral platelet inhibitors is associated with increased risk of fractures, and more studies are warranted to determine the potential effect of platelet inhibitors on bone metabolism in vivo.
authors.affiliation: The Osteoporosis Clinic, Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Vestergaard
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Steinberg
authors.forename: Peter
authors.initials: P
authors.lastname: Schwarz
authors.forename: Niklas Rye
authors.initials: NR
authors.lastname: Jørgensen
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D001241:Aspirin / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D000077144:Clopidogrel; D004176:Dipyridamole / Q000009:adverse effects* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D050723:Fractures, Bone / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000139:chemically induced* / Q000150:complications; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D012306:Risk; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D004176:Dipyridamole; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin