{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:09:05Z","timestamp":1772118545833,"version":"3.50.1"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T00:00:00Z","timestamp":1628726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JBMR Plus"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Atypical femur fractures (AFFs) are well\u2010established serious complication of long\u2010term bisphosphonate and denosumab therapy in patients with osteopenia or osteoporosis. To elucidate underlying mechanism(s) for the development of AFF, we performed a nested case\u2010control study to investigate bone tissue nanomechanical properties and prevailing bone microstructure and tissue\u2010level remodeling status as assessed by bone histomorphometry. We hypothesized that there would be differences in nanomechanical properties between patients with and without AFF and that bone microstructure and remodeling would be related to nanomechanical properties. Thirty\u2010two full\u2010thickness transiliac bone biopsies were obtained from age\u2010 and sex\u2010matched patients on long\u2010term bisphosphonate therapy with (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a016) and without an AFF (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a016). Standard histomorphometric measurements were made in each sample on three different bone envelopes (cancellous, intracortical, and endosteal). Iliac bone wall thickness was significantly lower on all three bone surfaces in patients with AFF than in those without AFF. Surface\u2010based bone formation rate was suppressed similarly in both groups in comparison to healthy premenopausal and postmenopausal women, with no significant difference between the two groups. Nanoindentation was used to assess material properties of cortical and cancellous bone separately. Elastic modulus was higher in cortical than in cancellous bone in patients with AFF as well as compared to the elastic modulus of cortical bone from non\u2010AFF patients. However, the elastic modulus of the cancellous bone was not different between AFF and non\u2010AFF groups or between cortical and cancellous bone of non\u2010AFF patients. Resistance to plastic deformation was decreased in cortical bone in both AFF and non\u2010AFF groups compared to cancellous bone, but to a greater extent in AFF patients. We conclude that long\u2010term bisphosphonate therapy is associated with prolonged suppression of bone turnover resulting in altered cortical remodeling and tissue nanomechanical properties leading to AFF. \u00a9 2021 The Authors.\n                    <jats:italic>JBMR Plus<\/jats:italic>\n                    published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.\n                  <\/jats:p>","DOI":"10.1002\/jbm4.10523","type":"journal-article","created":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T03:51:19Z","timestamp":1623815479000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Bone Nanomechanical Properties and Relationship to Bone Turnover and Architecture in Patients With Atypical Femur Fractures: A Prospective Nested Case\u2010Control Study"],"prefix":"10.1093","volume":"5","author":[{"given":"Lanny V.","family":"Griffin","sequence":"first","affiliation":[{"name":"California Polytechnic State University (Cal Poly)  San Luis Obispo CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Warner","sequence":"additional","affiliation":[{"name":"Bone &amp; Mineral Research Laboratory Henry Ford Health System\/Wayne State University Integrative Biosciences (IBio) Research Facility  Detroit MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saroj","family":"Palnitkar","sequence":"additional","affiliation":[{"name":"Bone &amp; Mineral Research Laboratory Henry Ford Health System\/Wayne State University Integrative Biosciences (IBio) Research Facility  Detroit MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shijing","family":"Qiu","sequence":"additional","affiliation":[{"name":"Bone &amp; Mineral Research Laboratory Henry Ford Health System\/Wayne State University Integrative Biosciences (IBio) Research 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