title: Bisphosphonate use and the risk of subtrochanteric or femoral shaft fractures in older women.
abstract: BACKGROUND
  Osteoporosis is associated with significant morbidity and mortality. Oral bisphosphonates have become a mainstay of treatment, but concerns have emerged that long-term use of these drugs may suppress bone remodeling, leading to unusual fractures.
  
  
  OBJECTIVE
  To determine whether prolonged bisphosphonate therapy is associated with an increased risk of subtrochanteric or femoral shaft fracture.
  
  
  METHODS
  A population-based, nested case-control study to explore the association between bisphosphonate use and fractures in a cohort of women aged 68 years or older from Ontario, Canada, who initiated therapy with an oral bisphosphonate between April 1, 2002, and March 31, 2008. Cases were those hospitalized with a subtrochanteric or femoral shaft fracture and were matched to up to 5 controls with no such fracture. Study participants were followed up until March 31, 2009.
  
  
  METHODS
  The primary analysis examined the association between hospitalization for a subtrochanteric or femoral shaft fracture and duration of bisphosphonate exposure. To test the specificity of the findings, the association between bisphosphonate use and fractures of the femoral neck or intertrochanteric region, which are characteristic of osteoporotic fractures, was also examined.
  
  
  RESULTS
  We identified 716 women who sustained a subtrochanteric or femoral shaft fracture following initiation of bisphosphonate therapy and 9723 women who sustained a typical osteoporotic fracture of the intertrochanteric region or femoral neck. Compared with transient bisphosphonate use, treatment for 5 years or longer was associated with an increased risk of subtrochanteric or femoral shaft fracture (adjusted odds ratio, 2.74; 95% confidence interval, 1.25-6.02). A reduced risk of typical osteoporotic fractures occurred among women with more than 5 years of bisphosphonate therapy (adjusted odds ratio, 0.76; 95% confidence interval, 0.63-0.93). Among 52,595 women with at least 5 years of bisphosphonate therapy, a subtrochanteric or femoral shaft fracture occurred in 71 (0.13%) during the subsequent year and 117 (0.22%) within 2 years.
  
  
  CONCLUSIONS
  Among older women, treatment with a bisphosphonate for more than 5 years was associated with an increased risk of subtrochanteric or femoral shaft fractures; however, the absolute risk of these fractures is low.
authors.affiliation: Institute for Clinical Evaluative Sciences, and Li Ka Shing Knowledge Institute of St. Michael's Hospital, 30 Bond St, Toronto, Ontario, M5B 1W8. parkwylliel@smh.ca
authors.forename: Laura Y
authors.initials: LY
authors.lastname: Park-Wyllie
authors.forename: Muhammad M
authors.initials: MM
authors.lastname: Mamdani
authors.forename: David N
authors.initials: DN
authors.lastname: Juurlink
authors.forename: Gillian A
authors.initials: GA
authors.lastname: Hawker
authors.forename: Nadia
authors.initials: N
authors.lastname: Gunraj
authors.forename: Peter C
authors.initials: PC
authors.lastname: Austin
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Whelan
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Weiler
authors.forename: Andreas
authors.initials: A
authors.lastname: Laupacis
mesh_terms: D000284:Administration, Oral; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D005260:Female; D005264:Femoral Fractures / Q000453:epidemiology* / Q000209:etiology; D006620:Hip Fractures / Q000453:epidemiology* / Q000209:etiology; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D016017:Odds Ratio; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control; D012306:Risk
chemical_list: D004164:Diphosphonates