Personalizing Osteoporosis Care: Clinical & Genetic Risk Factors for AFFs

The overall objective of this project is to identify clinical and genetic risk factors for Atypical Femur Fractures (AFFs) in Anti-resorptive therapy (ART) users by conducting a case control study of 330 cases of AFFs and 660 controls without AFFs matched for age, sex, race and duration of ART.

Antiresorptive therapy (ART) drugs are effective osteoporosis treatment and help decrease osteoporosis-related fractures. However, their long-term use has been associated with rare but serious atypical femur fractures (AFFs). Fear of these side effects has caused a substantial decline in the use of these effective drugs and rising fracture rates. The investigators propose to compare 330 cases of people with AFFs to 660 matched controls to explore similarities and differences in (1) clinical findings, such as type of ART and length of use, prior fracture, bone density, femur geometry, etc., and (2) genetic variants, and then (3) to validate the top few genetic variants to see if they are indeed present in an additional group of 100 AFF patients and not present in 100 control subjects. This study will determine clinical and genetic risk factors for these debilitating atypical fractures such that at-risk patients in the future can be treated differently to avoid them.