{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T17:07:22Z","timestamp":1787764042359,"version":"build-2784847793"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100002429","name":"Amgen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002429","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Bone &amp; Mineral Res"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Prolonged use of antiresorptives such as the bisphosphonate alendronate (ALN) and the RANKL inhibitor denosumab (DMAb) are associated with rare cases of atypical femoral fracture (AFF). The etiology of AFF is unclear, but it has been hypothesized that potent osteoclast inhibitors may reduce bone fatigue resistance. The purpose of this study was to quantify the relationship between antiresorptive treatment and fatigue life (cycles to failure) in bone from ovariectomized cynomolgus monkeys. We analyzed humeral bone from 30 animals across five treatment groups. Animals were treated for 12\u2009months with subcutaneous (sc) vehicle (VEH), sc DMAb (25\u2009mg\/kg\/month), or intravenous (iv) ALN (50\u2009\u03bcg\/kg\/month). Another group received 6\u2009months VEH followed by 6\u2009months DMAb (VEH\u2010DMAb), and the final group received 6\u2009months ALN followed by 6\u2009months DMAb (ALN\u2010DMAb). A total of 240 cortical beam samples were cyclically tested in four\u2010point bending at 80, 100, 120, or 140\u2009MPa peak stress. High\u2010resolution imaging and density measurements were performed to evaluate bone microstructure and composition. Samples from the ALN (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u20090.014), ALN\u2010DMAb (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u20090.008), and DMAb (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u20090.001) groups illustrated higher fatigue\u2010life measurements than VEH. For example, at 140\u2009MPa the VEH group demonstrated a median\u2009\u00b1\u2009interquartile range (IQR) fatigue life of 1987\u2009\u00b1\u200910593\u2009cycles, while animals in the ALN, ALN\u2010DMAb, and DMAb groups survived 9850\u2009\u00b1\u200913648 (+395% versus VEH), 10493\u2009\u00b1\u200916796 (+428%), and 14495\u2009\u00b1\u200949299 (+629%) cycles, respectively. All antiresorptive treatment groups demonstrated lower porosity, smaller pore size, greater pore spacing, and lower number of canals versus VEH (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u20090.001). Antiresorptive treatment was also associated with greater apparent density, dry density, and ash density (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0\u2264\u20090.03). We did not detect detrimental changes following antiresorptive treatments that would explain their association with AFF. In contrast, 12\u2009months of treatment may have a protective effect against fatigue fractures. \u00a9 2022 American Society for Bone and Mineral Research (ASBMR).\n                  <\/jats:p>","DOI":"10.1002\/jbmr.4758","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T07:23:24Z","timestamp":1671434604000},"page":"403-413","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Twelve Months of Denosumab and\/or Alendronate Is Associated With Improved Bone Fatigue Life, Microarchitecture, and Density in Ovariectomized Cynomolgus Monkeys"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6445-7291","authenticated-orcid":false,"given":"Ifaz T.","family":"Haider","sequence":"first","affiliation":[{"name":"Human Performance Lab, Faculty of Kinesiology University of Calgary  Calgary AB Canada"},{"name":"McCaig Institute for Bone and Joint Health, Cumming School of Medicine University of Calgary  Calgary AB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay L.","family":"Loundagin","sequence":"additional","affiliation":[{"name":"Human Performance Lab, Faculty of Kinesiology University of Calgary  Calgary AB Canada"},{"name":"McCaig Institute for Bone and Joint Health, Cumming School of Medicine University of Calgary  Calgary AB Canada"},{"name":"Department of Anatomy, Physiology and Pharmacology University of Saskatchewan  Saskatoon SK Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3995-4306","authenticated-orcid":false,"given":"Andrew","family":"Sawatsky","sequence":"additional","affiliation":[{"name":"Human Performance Lab, Faculty of Kinesiology University of Calgary  Calgary AB Canada"},{"name":"McCaig Institute for Bone and Joint Health, Cumming School of Medicine University of Calgary  Calgary AB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7209-1368","authenticated-orcid":false,"given":"Paul J.","family":"Kostenuik","sequence":"additional","affiliation":[{"name":"Phylon Pharma Services  Newbury Park CA USA"},{"name":"School of Dentistry University of Michigan (Adjunct)  Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2930-5997","authenticated-orcid":false,"given":"Steven K.","family":"Boyd","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone and Joint Health, Cumming School of Medicine University of Calgary  Calgary AB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3623-9764","authenticated-orcid":false,"given":"W. 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