Even though these fractures are relatively rare, recent data show “consistent evidence of increased AFF incidence with longer duration of bisphosphonate treatment, especially greater than five years,” said Dr. Shane.14
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In a 2020 study of 1.1 million women aged 50 and older, including 18% who had used bisphosphonates, incidence of atypical femur fractures was very low, or 1.74 cases per 10,000 person-years, and very few cases were seen among women who had never taken the drugs. AFFs were highest among women between ages 65 and 84, and more prevalent in Asian women than white women. AFF incidence decreased over the time span since the women discontinued bisphosphonates, the study found. “Within just three months of stopping, incidence of AFFs decreased markedly,” encouraging data for people who are considering a drug holiday, Dr. Shane said.
According to the study, important risk factors for AFFs include glucocorticoid use, shorter height and higher body weight, but no association was found between AFF risk and bone mineral density, and no statistically significant increased risk among women who smoke. The estimated number of hip and clinical fractures prevented by five years of bisphosphonates outweighed the number of AFFs in both white and Asian women in the study.15
We have to find more effective ways to communicate that osteoporotic fractures have devastating effects on people’s lives.—Elizabeth Shane, MD
Atypical Femur Fractures Pathogenesis
Because AFFs often cause prodromal pain, unlike other hip fractures, they may have a distinct pathogenesis, and “it’s very likely that they are a form of stress or insufficiency fracture,” Dr. Shane said. AFFs affect bones subjected to repetitive loading, and microcracks often develop in areas where tensional stress is high, or where the convex curve of the femur straightens and tensile forces concentrate.12
“We also think that there is increased homogeneity of osteons, because bisphosphonates increase tissue age and mineralization, permitting these microcracks to accumulate and coalesce over time, then gradually aggregate and propagate across the bone,” Dr. Shane explained.
Women with a varus hip angle, bowed femurs or smaller bones may be at risk for AFFs, because these factors place stress on the lateral femur, she said. This extra stress may account for cortical thickening common in AFFs, but is not associated with bisphosphonate use.16
Stress fractures also heal differently, which may lead to delayed healing. “They heal by osteoclasts resorbing damaged bone and then osteoblasts depositing new bone at that site.17 But bisphosphonates localize at the site of microdamage and stress fractures, and they inhibit osteoclast-mediated bone resorption. Over time, bisphosphonates could both facilitate the development of microcracks and delay their repair, allowing them to progress to a stress fracture,” Dr. Shane said.18