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Bisphosphonate-related atypical femoral fracture: Managing a rare but serious complication

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Release date: November 1, 2018
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ABSTRACT

Atypical femoral fracture is a rare but serious complication of long-term bisphosphonate therapy. Although the benefit of preventing osteoporotic fractures greatly outweighs the risk of atypical fracture in bisphosphonate users, concern about atypical fracture risk has led to a decrease in bisphosphonate use. What are the risks, and how do we treat atypical femoral fracture?

KEY POINTS

  • The benefits of bisphosphonate therapy in reducing fracture risk outweigh the risk of atypical fracture.
  • Bisphosphonate use for longer than 5 years greatly increases the risk of atypical femoral fracture.
  • Treatment of atypical femoral fracture varies depending on whether the patient has pain and whether the fracture is complete or incomplete.


 

References

Bisphosphonate therapy minimizes bone loss and reduces fracture risk by up to 50% in patients with osteoporosis,1 but it is also associated with increased risks of osteonecrosis of the jaw and atypical femoral fracture. Although atypical femoral fractures are rare, they can have a devastating effect. Patient concern about this complication has contributed to a decrease in bisphosphonate use by about half in the last decade or so,2,3 and we fear this could result in an increase in hip fracture rates.

In this article, we examine the evidence on bisphosphonate-associated atypical femoral fractures, including risks, pathogenesis, treatment, and prevention.

ATYPICAL FRACTURES INVOLVE THE FEMORAL SHAFT, NOT THE HEAD

An atypical femoral fracture is a transverse fracture of the femoral shaft (diaphysis), defined by both clinical criteria and radiographic appearance.

To be defined as atypical, a femoral fracture must meet 4 of the following 5 criteria4:

  • Occurs with minimal or no trauma
  • Has a predominantly transverse fracture line, originating at the lateral cortex and sometimes becoming oblique as it progresses medially across the femur
  • Extends through both cortices and may be associated with a medial spike (complete fractures); or involves only the lateral cortex (incomplete fractures)
  • Is noncomminuted or minimally comminuted
  • Shows localized periosteal or endosteal thickening (termed “beaking” or “flaring”) of the lateral cortex at the fracture site.

Several minor features are also important but are not required, eg:

  • Cortical thickening of the femoral shaft
  • Unilateral or bilateral prodromal pain preceding the fracture
  • Bilateral incomplete or complete femoral diaphysis fractures
  • Delayed fracture healing.

Atypical femoral fracture can occur anywhere along the shaft, from just distal to the lesser trochanter to just proximal to the supracondylar flare. However, most occur in 2 areas, with 1 cluster centered at about 41 mm from the lesser trochanter (more common in relatively younger patients) and the other at 187 mm.5

ABSOLUTE RISK IS LOW BUT INCREASES WITH LONGER USE

Atypical femoral fractures are rare. Schilcher et al6 reviewed radiographs of 1,234 women who had a subtrochanteric or shaft fracture and found 59 (4.6%) of fractures were atypical. In a systematic review of 14 studies,7 the incidence ranged from 3.0 to 9.8 cases per 100,000 patient-years.

Furthermore, not all atypical femoral fractures are in bisphosphonate users: 7.4% were in nonusers in 1 series8 and 22% in another.9

Nevertheless, most studies show that bis­phosphonate use increases the incidence of atypical femoral fracture, and the incidence increases with duration of use, especially after 3 years.7

An international task force of the American Society for Bone and Mineral Research listed the absolute risk as between 3.2 and 50 cases per 100,000 patient-years, with longer use (> 5 years) increasing the risk to about 100 per 100,000 patient-years.4 After stopping bis­phosphonate therapy, the risk diminished by 70% per year.9

In another study, for 0.1 to 1.9 years of therapy, the age-adjusted atypical fracture rates were 1.78 per 100,000 per year (95% confidence interval [CI] 1.5–2.0), increasing to 113.1 per 100,000 per year (95% CI 69.3–156.8) with exposure from 8 to 9.9 years.10

A case-control study found that more than 5 years of bisphosphonate use increased the fracture risk by an odds ratio of 2.74 (95% CI 1.25–6.02).11

The incidence of typical femoral fracture was higher in those who adhered better to their oral bisphosphonate regimen in some studies,12 but the opposite was true in others.13

The benefits of bisphosphonate therapy in reducing fracture risk, however, outweigh the risk of atypical fracture.4

We do not know whether the rate of atypical femoral fracture is increasing. A review of Kaiser Permanente Northwest records found that the rates of atypical femoral shaft fracture had remained stable from 1996 to 2009. However, 61.9% of patients who met the strict radiographic criteria had taken oral bisphosphonates.14 These data suggest that bisphosphonate use has not increased the overall population-based risk for subtrochanteric and femoral shaft fractures, but that bisphosphonates and other risk factors may have increased the likelihood that such fractures will exhibit atypical radiographic features.

A population-based study in Denmark13 found that alendronate use longer than 10 years was associated with an adjusted 30% lower risk of hip fracture and no increase in the risk of subtrochanteric and femoral shaft fracture. In addition, the risk of subtrochanteric and femoral shaft fracture was lower with high adherence to alendronate treatment (based on medication possession ratio > 80%) compared with low adherence (ratio < 50%) (odds ratio 0.88, 95% CI 0.77–0.99). The risk was not increased in current vs past users.

The Danish study13 used the coding of the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) to identify subtrochanteric and femoral shaft fractures without radiologic review for atypical radiographic features. The lack of specific ICD-10 coding for subtrochanteric and femoral shaft fractures with atypical radiographic features has limited our knowledge of their incidence.

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