Atypical femur fracture incidence in women increases with duration of bisphosphonate exposure

Abstract

The age-adjusted incidence of atypical femur fracture (AFF) reported in southern California increased with bisphosphonate (BP) exposure, ranging up to 113 per 100,000 person-years for 8-10-year exposure. This study examines the incidence of AFF in a northern California population. Women age 45-89years who initiated oral BP during 2002-2014 in Kaiser Permanente Northern California were followed for AFF outcome, defined by a primarily transverse diaphyseal femur fracture through both cortices, with focal periosteal/endosteal hypertrophy, minimal trauma, and minimal/no comminution. Total BP exposure was determined from dispensed prescriptions. The incidence of AFF, calculated for 2-year BP categories ranging from < 2 to > 10years, was age-adjusted using the 2000 US Census. Among 94,542 women, 107 experienced an AFF during or < 1year after BP cessation (mean exposure 6.6 ± 3.0years and total days' supply 5.7 ± 2.8years at AFF). A strong relationship between AFF incidence and increasing BP exposure was seen, more than doubling for each 2-year category until 8-10years. Among women with 2- to < 4-year BP, the crude and age-adjusted incidence was 18 and 9 per 100,000 person-years but increased over 2- and 5-fold for women with 4- to < 6- and 6- to < 8-year BP, respectively. For those receiving ≥ 8-year BP, the crude and age-adjusted incidence peaked at 196 and 112 per 100,000 person-years exposure. Incidence of AFF increases markedly after 4-6years of BP. These trends align with southern California and confirm a strong BP duration-related risk of this rare but serious event.