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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2017,8,15]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Since the first reports of atypical femoral fractures (AFFs), a clinical phenomenon in which patients experience catastrophic brittle fractures of the femoral shaft with minimal trauma, the risk associated with bisphosphonates, the most widely prescribed pharmaceuticals for osteoporosis, has become increasingly well-established. However, the underlying cause of AFFs and their causal relationship to bisphosphonates is unknown. Here we examine bone tissue from women with AFFs and show that long-term bisphosphonate treatment degrades the fracture-resistance toughening mechanisms that are inherent to healthy bone. 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