atypical femoral neck fracture and bisphosphonates

Last edited 08/2020 and last reviewed 12/2021

Atypical femoral fracture is a rare adverse effect of bisphosphonates reported in patients receiving long-term treatment for osteoporosis (1).

• it is considered a class effect of bisphosphonates
  • a Europe-wide review of bisphosphonates and atypical stress fractures conducted in 2008 reported that an increased risk of atypical stress fractures of the proximal femoral shaft was seen in patients using alendronic acid, but a further Europe-wide review carried out on this subject in May 2011 concluded that atypical fractures of the femur may occur rarely with the use of any bisphosphonate (1) These fractures are often bilateral and may occur after minimal or no trauma
    
    
• the contralateral femur should be examined in bisphosphonate treated patients who presents with a femoral shaft fracture
  
  
• some patients may experience thigh or groin pain (often associated with features of stress fractures on radiograph) weeks or months before presenting with a completed femoral fracture
  
  
• poor healing of these fractures has also been reported (1)

Discontinuation of bisphosphonate therapy should be considered in patients who are suspected to have an atypical femur fracture

• the decision should be based on an assessment of the benefits and risks of treatment for the individual
• patients should be advised to report any thigh, hip, or groin pain and anyone reporting such symptoms should be evaluated for an incomplete femur fracture

The need for continued therapy with bisphosphonates should be re-evaluated in individual patients at regular intervals based on the benefits and potential risks, particularly after 5 or more years of use (1)

• the reported cases of atypical fractures are far lower than the number of osteoporotic fractures prevented (1)
• balance of risks and benefits of individual bisphosphonates in their authorised indications remain favourable

Black et al (2) studied women 50 years of age or older who were receiving bisphosphonates - women were followed from January 1, 2007, to November 30, 2017. The primary outcome was atypical femur fracture. Data on risk factors, including bisphosphonate use, were obtained from electronic health records. Fractures were radiographically adjudicated

• among 196,129 women, 277 atypical femur fractures occurred
• risk of atypical fracture increased with longer duration of bisphosphonate use:
• the hazard ratio as compared with less than 3 months increased from 8.86 (95% confidence interval [CI], 2.79 to 28.20) for 3 years to less than 5 years to 43.51 (95% CI, 13.70 to 138.15) for 8 years or more
• other risk factors included race (hazard ratio for Asians vs. Whites, 4.84; 95% CI, 3.57 to 6.56), height, weight, and glucocorticoid use
• bisphosphonate discontinuation was associated with a rapid decrease in the risk of atypical fracture
• decreases in the risk of osteoporotic and hip fractures during 1 to 10 years of bisphosphonate use far outweighed the increased risk of atypical fracture among Whites but less so among Asians
• after 3 years, 149 hip fractures were prevented and 2 bisphosphonate-associated atypical fractures occurred in Whites, as compared with 91 and 8, respectively, in Asians
• study authors concluded that:
• risk of atypical femur fracture increased with longer duration of bisphosphonate use and rapidly decreased after bisphosphonate discontinuation
• Asians had a higher risk than Whites
• absolute risk of atypical femur fracture remained very low as compared with reductions in the risk of hip and other fractures with bisphosphonate treatment

Reference:

• 1. Medicines and Healthcare products Regulatory Agency (MHRA). Bisphosphonates: atypical femoral fractures. Drug Safety Update 2011;4(11)
• 2. Black DM et al.Atypical Femur Fracture Risk versus Fragility Fracture Prevention with Bisphosphonates. N Engl J Med 2020; 383:743-753