Bone Abstracts

Background: Bisphosphonate use is associated with an increased risk of atypical femoral fractures in women. The risk in men and the risk pattern dependent on treatment duration, recent use and type of bisphosphonate however remains unclear.

Methods: All 5715 Swedish men and women, 55 years or older, with a fracture of the femoral shaft in the three-year period 2008–2010 were identified by the national patient registry. Radiographs were reviewed and we found 160 female and 12 male patients with atypical fracture. Medical background information was also obtained from register data. The relative and absolute risk of atypical fractures associated with bisphosphonate use was estimated in a nationwide cohort analysis. The 172 case patients were compared with 952 control patients with ordinary shaft fractures.

Results: The age-adjusted relative risk (RR) of atypical fracture in the cohort analysis was 55 (95% CI 39 to 79) in women and 54 (CI 15-192) in men. Among bisphosphonate users, women had a three-fold higher risk (RR 3.08; CI 1.13–8.42) compared to men. The average absolute risk with bisphosphonate use was 5 per 10 000 (CI 4 to 6) person-years of use in women and 2 per 10 000 (CI 0 to 3) in men. The relative risk increased for every year of use and reached 126 (CI 55 to 288) after 4 or more years. The multivariable-adjusted odds ratio of sustaining an atypical fracture after 4–5 years of bisphosphonate use was 116 (CI 58–234). The risk diminished by 70% for each year after cessation of treatment. The odds with alendronate use was 3 times higher than with risedronate use.

Conclusion: Women have a higher risk of atypical fracture than men. The risk-benefit ratio for bisphosphonate deteriorates with long-term treatment. The rapid decrease in risk after cessation suggests that the pathophysiological mechanism is related to targeted remodeling.