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No real explanations for the mechanisms underlying the basis for development of where AFF develop while on BPs has emerged. The present hypothesis will discuss the possibility that part of the risk for an AFF is a secondary effect of BPs on a subset of vascular cells in a genetically at\u2010risk population, leading to localized deregulation of the endothelial cell (EC)\u2010bone cell\u2010matrix units in nutrient channels\/canals of the femur and increased risk for AFF. This concept of targeting ECs is consistent with location of AFF in the femur, the bilateral risk for occurrence of AFF, and the requirement for long term exposure to the drugs.<\/jats:p>","DOI":"10.1002\/bies.202200206","type":"journal-article","created":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T08:32:45Z","timestamp":1676881965000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Are secondary effects of bisphosphonates on the vascular system of bone contributing to increased risk for atypical femoral fractures in osteoporosis?"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8580-294X","authenticated-orcid":false,"given":"David A.","family":"Hart","sequence":"first","affiliation":[{"name":"Department of Surgery Faculty of Kinesiology McCaig Institute for Bone &amp; Joint Health University of Calgary  Calgary Alberta 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