{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:46:45Z","timestamp":1790830005786,"version":"4.1.0"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T00:00:00Z","timestamp":1613001600000},"content-version":"vor","delay-in-days":72,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"INSERM UMR 1033","award":["Operational grant"],"award-info":[{"award-number":["Operational grant"]}]},{"DOI":"10.13039\/100000069","name":"NIH\/NIAMS","doi-asserted-by":"publisher","award":["grant AR062103"],"award-info":[{"award-number":["grant AR062103"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["grant AR062103"],"award-info":[{"award-number":["grant AR062103"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Bisphosphonates (BPs) are the most widely used drugs for the treatment of osteoporosis but prolonged use of BPs might increase the risk of atypical femur fracture (AFF). There are only a few studies that address the bone material quality in patients on long-term BP treatment with or without AFFs. We analyzed 52 trans-iliac bone biopsies from patients on long-term BP therapy with (n\u00a0=\u00a026) and without (n\u00a0=\u00a026) AFF. At the microscopic level, the degree of mineralization of bone (DMB) was assessed on whole bone by X-ray digitized microradiography while microhardness by Vickers microindentation, and bone matrix characteristics by Fourier transform infrared microspectroscopy (FTIRM) (mineral\/organic ratio, mineral maturity and crystallinity, and collagen maturity) were measured at random focal areas. The AFF patients were treated longer than non-AFF patients (9.7\u2009\u00b1\u20093.3\u2009years versus 7.9\u2009\u00b1\u20092.7\u2009years). As expected, bone remodeling was low in both groups, without difference between them. The AFF group had significantly higher DMB in cortical bone (+2.9%, p\u00a0=\u00a0.001), which remained so after adjusting for treatment duration (p\u00a0=\u00a0.007), and showed a trend in cancellous bone (+1.6%, p\u00a0=\u00a0.05). Consistent with higher DMB, heterogeneity index (HI) was lower in the AFF than in the non-AFF group, illustrating lower heterogeneity of mineralization in the AFF group. A significant positive correlation between the duration of treatment and DMB in cortical bone was found in AFF, and not in the non-AFF group. Microhardness and bone matrix characteristics were similar between groups. We conclude that the AFF group had a duration-dependent increase in DMB leading to a significantly higher DMB than the non-AFF. Because BPs have high affinity to bone mineral and lining the walls of the osteocyte lacunae, the accumulation of matrix-bound BPs in AFF could lead to inhibition of the osteocyte cytoskeleton blunting their response to mechanical strains, a hypothesis to be further investigated. \u00a9 2021 American Society for Bone and Mineral Research (ASBMR).<\/jats:p>","DOI":"10.1002\/jbmr.4244","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T05:00:09Z","timestamp":1610686809000},"page":"1031-1041","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Duration-Dependent Increase of Human Bone Matrix Mineralization in Long-Term Bisphosphonate Users with Atypical Femur Fracture"],"prefix":"10.1093","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6487-0337","authenticated-orcid":false,"given":"Delphine","family":"Farlay","sequence":"first","affiliation":[{"name":"INSERM, Unit\u00e9s Mixtes de Recherche (UMR) 1033, Universit\u00e9 de Lyon Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Rizzo","sequence":"additional","affiliation":[{"name":"INSERM, Unit\u00e9s Mixtes de Recherche (UMR) 1033, Universit\u00e9 de Lyon Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis-Georges","family":"Ste-Marie","sequence":"additional","affiliation":[{"name":"Department of Medicine Universit\u00e9 de Montr\u00e9al Montr\u00e9al Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"La\u00ebtitia","family":"Michou","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Centre Hospitalier Universitaire (CHU) de Qu\u00e9bec-Universit\u00e9 Laval Research Centre Quebec City Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4317-492X","authenticated-orcid":false,"given":"Suzanne N","family":"Morin","sequence":"additional","affiliation":[{"name":"Department of Medicine McGill University Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijing","family":"Qiu","sequence":"additional","affiliation":[{"name":"Bone & Mineral Research Laboratory Henry Ford Health System Detroit MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5128-7361","authenticated-orcid":false,"given":"Pascale","family":"Chavassieux","sequence":"additional","affiliation":[{"name":"INSERM, Unit\u00e9s Mixtes de Recherche (UMR) 1033, Universit\u00e9 de Lyon Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8214-6385","authenticated-orcid":false,"given":"Roland D","family":"Chapurlat","sequence":"additional","affiliation":[{"name":"INSERM, Unit\u00e9s Mixtes de Recherche (UMR) 1033, Universit\u00e9 de Lyon Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2200-1800","authenticated-orcid":false,"given":"Sudhaker D","family":"Rao","sequence":"additional","affiliation":[{"name":"Bone & Mineral Research Laboratory Henry Ford Health System Detroit MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1910-788X","authenticated-orcid":false,"given":"Jacques P","family":"Brown","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Centre Hospitalier Universitaire (CHU) de Qu\u00e9bec-Universit\u00e9 Laval Research Centre Quebec City Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3594-5699","authenticated-orcid":false,"given":"Georges","family":"Boivin","sequence":"additional","affiliation":[{"name":"INSERM, Unit\u00e9s Mixtes de Recherche (UMR) 1033, Universit\u00e9 de Lyon Lyon 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