Reports of atypical femoral fractures (AFFs) have created uncertainty about the duration of bisphosphonate or receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor therapy for bone health in both patients with cancer and osteoporosis, despite the fact that they are uncommon consequences of treatment for osteoporosis, osteopenia, and bony metastasis. This evidence concerns the gene TNFSF11 and osteoporosis.