Abstract
Background
Bisphosphonates are effective in reducing hip and osteoporotic fractures. However, concerns about atypical femoral fractures have contributed to substantially reduced use of bisphosphonate, and the incidence of hip fractures may increase. Significant uncertainties remain about the association between atypical femoral fractures and bisphosphonates and other risk factors.
Methods
We study women aged 50 or older who received bisphosphonates and who were enrolled in the Kaiser Permanente health care system in Southern California; women were followed from January 1, 2007, to November 30, 2017. The primary outcome was atypical femoral fracture. Data on risk factors, including use of bisphosphonate, were obtained from electronic health records. Fractions were radiographically assessed. Multivariable Cox models were used. The risk-benefit profile was modeled for 1 to 10 years of use of bisphosphonate to compare associated atypical fractures with other common fractures.
The results
Among 196,129 women, there were 277 atypical femoral fractures. After multivariate adjustment, the risk of atypical fracture increased with prolonged use of bisphosphonate: the hazard ratio increased from 8,86 (95% confidence interval compared to less than 3 months) [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. Discontinuation of bisphosphonate was associated with a rapid decrease in the risk of atypical fracture. Reducing the risk of osteoporotic and hip fractures during 1 to 10 years of bisphosphonate use was more severe than the increased risk of atypical fracture among whites, but less than among Asians. After 3 years, 149 hip fractures were prevented and 2 animal phosphonate-associated atypical fractures occurred in Whites, compared with 91 and 8, respectively, in Asians.
Conclusions
The risk of atypical femoral fracture increased with prolonged duration of bisphosphonate use and decreased rapidly after stopping bisphosphonate. Asians had a higher risk than whites. The absolute risk of atypical femoral fracture remained very low compared to reduction in the risk of hip and other fractures with bisphosphonate treatment. (Funded by Kaiser Permanente and others.)
