title: Myocardial infarction risk among patients with fractures receiving bisphosphonates.
abstract: OBJECTIVE
  To determine if bisphosphonates are associated with reduced risk of acute myocardial infarction (AMI).
  
  
  METHODS
  A cohort of 14,256 veterans 65 years or older with femoral or vertebral fractures was selected from national administrative databases operated by the US Department of Veterans Affairs and was derived from encounters at Veterans Affairs facilities between October 1, 1998, and September 30, 2006. The time to first AMI was assessed in relationship to bisphosphonate exposure as determined by records from the Pharmacy Benefits Management Database. Time to event analysis was performed using multivariate Cox proportional hazards regression. An adjusted survival analysis curve and a Kaplan-Meier survival curve were analyzed.
  
  
  RESULTS
  After controlling for atherosclerotic cardiovascular disease risk factors and medications, bisphosphonate use was associated with an increased risk of incident AMI (hazard ratio, 1.38; 95% CI, 1.08-1.77; P=.01). The timing of AMI correlated closely with the timing of bisphosphonate therapy initiation.
  
  
  CONCLUSIONS
  Our observations in this study conflict with our hypothesis that bisphosphonates have antiatherogenic effects. These findings may alter the risk-benefit ratio of bisphosphonate use for treatment of osteoporosis, especially in elderly men. However, further analysis and confirmation of these findings by prospective clinical trials is required.
authors.affiliation: Mercy Arthritis and Osteoporosis Center, Urbandale, IA. Electronic address: cpittman@mercydesmoines.org.
authors.forename: Cory B
authors.initials: CB
authors.lastname: Pittman
authors.affiliation: Denver Health and Hospital Authority, Denver, CO; Denver Veterans Affairs Medical Center, Denver, CO; University of Colorado School of Medicine, Aurora, CO.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Davis
authors.affiliation: Department of Medicine, St. Louis Veterans Affairs Medical Center, Washington University School of Medicine, St. Louis, MO.
authors.forename: Angelique L
authors.initials: AL
authors.lastname: Zeringue
authors.affiliation: Denver Veterans Affairs Medical Center, Denver, CO; University of Colorado School of Medicine, Aurora, CO.
authors.forename: Liron
authors.initials: L
authors.lastname: Caplan
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Florida College of Medicine-Jacksonville, St. Louis, MO.
authors.forename: Kent R
authors.initials: KR
authors.lastname: Wehmeier
authors.affiliation: Department of Psychiatry, St. Louis Veterans Affairs Medical Center, Washington University School of Medicine, St. Louis, MO.
authors.forename: Jeffrey F
authors.initials: JF
authors.lastname: Scherrer
authors.affiliation: Department of Biostatistics, St. Louis University College for Public Health & Social Justice, St. Louis, MO.
authors.forename: Hong
authors.initials: H
authors.lastname: Xian
authors.affiliation: Veterans Affairs Pharmacy Benefits Management, Hines, IL.
authors.forename: Francesca E
authors.initials: FE
authors.lastname: Cunningham
authors.affiliation: Department of Medicine, St. Louis Veterans Affairs Medical Center, Washington University School of Medicine, St. Louis, MO.
authors.forename: Jay R
authors.initials: JR
authors.lastname: McDonald
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Florida College of Medicine-Jacksonville, St. Louis, MO; St. Olaf College, Northfield, MN.
authors.forename: Alexis
authors.initials: A
authors.lastname: Arnold
authors.affiliation: Veterans Affairs Health Service Research and Development, Washington, DC.
authors.forename: Seth A
authors.initials: SA
authors.lastname: Eisen
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000009:adverse effects; D015984:Causality; D015331:Cohort Studies; D015897:Comorbidity; D016208:Databases, Factual / Q000706:statistics & numerical data; D004164:Diphosphonates / Q000009:adverse effects*; D005260:Female; D005264:Femoral Fractures / Q000188:drug therapy / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D008297:Male; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000453:epidemiology*; D010024:Osteoporosis / Q000188:drug therapy* / Q000453:epidemiology*; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors; D016103:Spinal Fractures / Q000188:drug therapy / Q000453:epidemiology*; D016019:Survival Analysis; D014481:United States / Q000453:epidemiology; D014493:United States Department of Veterans Affairs / Q000706:statistics & numerical data; D014728:Veterans
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates
keywords: AMI; BMD; HR; ICD-9-CM; International Classification of Diseases, Ninth Revision, Clinical Modification; NCBP; VA; Veterans Affairs; acute myocardial infarction; bone mineral density; hazard ratio; nitrogen-containing bisphosphonate