Atypical femur fracture risk increases with longer bisphosphonate use, drops after discontinuation
Researchers studied women ages 50 years or older who took bisphosphonates and were enrolled in the Kaiser Permanente Southern California health care system.
Among women who used bisphosphonates, the absolute risk of atypical femur fracture risk was very low compared to reductions in the risk of hip and other fractures and rapidly decreased after bisphosphonate discontinuation, a recent study found.
Researchers studied women ages 50 years or older who took bisphosphonates and were enrolled in the Kaiser Permanente Southern California health care system. Kaiser Permanente was one funding source, and the study began with a pilot grant from Merck Sharp & Dohme, which had no role in the conduct of the study and did not see or review results.
Patients were followed from January 2007 to November 2017. The primary outcome was atypical femur fracture, as recorded in electronic health records. The effects of one to 10 years of bisphosphonate use on risk of associated atypical fractures versus benefit of other fracture prevention were modeled. Results were published by the New England Journal of Medicine on Aug. 20.
Among 196,129 women, 277 atypical femur fractures occurred and 9,102 hip fractures occurred. After multivariable adjustment, the risk for atypical fracture increased with longer duration of bisphosphonate use. Compared with less than three months of use, the hazard ratio was 8.86 (95% CI, 2.79 to 28.20) for three to less than five years of use and 43.51 (95% CI, 13.70 to 138.15) for eight years or more of use. Stopping bisphosphonate therapy was associated with a rapid decrease in the risk for atypical fracture (4.50 per 10,000 person-years among current users, 1.81 per 10,000 person-years at >3 to 15 mo since discontinuation, and approximately 0.50 per 10,000 person-years at >15 mo after discontinuation).
Other risk factors for atypical fracture included race. Asian women had higher rates of atypical fracture than white women (5.95 vs. 1.09 per 10,000 person-years; hazard ratio for Asian women vs. white women, 4.84 [95% CI, 3.57 to 6.56]) but lower rates of hip fracture. Decreases in the risk of osteoporotic and hip fractures associated with one to 10 years of bisphosphonate use far outweighed the increased risk of atypical fracture among white women but less so among Asian women, the authors noted. With three years of therapy, 149 hip fractures were prevented and two bisphosphonate-associated atypical fractures occurred in white women, as compared with 91 and eight, respectively, in Asian women.
“We found that the risk of atypical femur fracture increased significantly with longer duration of bisphosphonate treatment—particularly beyond 5 years of use—even after multivariate adjustment in this diverse cohort of bisphosphonate-treated patients,” the authors wrote. “It is important that the absolute risk of atypical femur fracture remained small as compared with risks of other osteoporotic fractures, most obviously in Whites, although the risk-benefit balance appeared less favorable for Asian women.”
The authors noted that the reduction in atypical fractures with discontinuation might support drug holidays, but the effects on other osteoporotic fractures must also be considered.