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Atypical Femoral Fractures and Bisphosphonate Use
  N Engl J Med 2010; 362:1848-1849May 13, 2010
To the Editor:
Since 2007, there have been several reports suggesting a potential association between the use of bisphosphonates and the occurrence of subtrochanteric or so-called atypical femoral fracture.1-4 However, a recent registry-based cross-sectional study did not show a greater frequency of such fractures in patients receiving alendronate.5 Thus, the association between atypical femoral fractures and bisphosphonate use remains an open issue.
We reviewed 152 femoral fractures (not including hip) that occurred in 152 patients who were admitted to a tertiary center during a 60-month period from June 2003 through May 2008. The mean (±SD) age of the patients was 78±5 years, and 132 of the patients were women. A senior orthopedic surgeon who was unaware of the patients' baseline characteristics and medication use reviewed the fracture radiographs of every patient in random sequence on two separate occasions (Cohen's k=0.8), identifying those fractures that fit the criteria for an atypical fracture (i.e., a lateral transverse or <30-degree oblique fracture line in an area of cortical thickening with a medial unicortical beak), as described previously.3,4
Twenty of the 152 fractures were classified as atypical. After unblinding of the database, 17 patients in this group were found to be receiving current oral bisphosphonate treatment. Of these patients, 15 were taking alendronate (mean treatment duration, 5.1 years), and 2 were taking risedronate (mean treatment duration, 3 years). Of the 132 patients whose radiographs did not fulfill the criteria for atypical fracture, 2 patients (1.5%) were taking alendronate, and 1 patient was taking risedronate (0.8%), with mean treatment durations of 3.5 years and 1 year, respectively.The atypical fracture pattern appeared to be 96.7% specific to patients receiving bisphosphonates.
Several additional risk factors were associated with atypical femur fracture. These included a history of low-energy fracture (odds ratio, 3.2; 95% confidence interval [CI], 2.1 to 17.1; P<0.001), the use of glucocorticoid therapy for more than 6 months (odds ratio, 5.2; 95% CI, 1.3 to 31.0; P=0.01), active rheumatoid arthritis (odds ratio, 16.5; 95% CI, 1.4 to 142.3; P<0.001), and a level of serum 25-hydroxyvitamin D of less than 16 ng per milliliter (40 nmol per liter) (odds ratio, 3.5; 95% CI, 1.7 to 18.7; P<0.001).
Although there is an association between atypical subtrochanteric femur fracture and oral bisphosphonate use, clinicians should remember that bisphosphonates significantly reduce the risk of fragility fractures in patients with osteoporosis and that overall the antifracture effects of bisphosphonates far outweigh their potential risks.
Christian M. Girgis, M.B., B.S.
Doron Sher, M.B., B.S., F.R.A.C.S.
Markus J. Seibel, M.D., Ph.D.
University of Sydney, Sydney, NSW, Australia
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