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We established inferior alveolar nerve injury (IANI) and inferior alveolar nerve transection (IANT) models characterized by disorganized periosteum, increased osteoclasts, and unbalanced neuropeptide expression. Zoledronate injection disrupted neuropeptide expression <jats:bold>in the IANI and IANT models<\/jats:bold> by decreasing calcitonin gene\u2013related peptide (CGRP) and increasing substance P (SP); associated with this, BRONJ prevalence was significantly higher in the IANT model, followed by the IANI model and the sham control. CGRP treatment significantly reduced BRONJ occurrence, whereas SP administration had the opposite effect. <jats:italic>In vitro<\/jats:italic>, RAW 264.7 cells were treated with BPs and then CGRP and\/or SP to study changes in zoledronate toxicity; combined application of CGRP and SP decreased zoledronate toxicity, whereas CGRP or SP applied alone showed no effects. These results demonstrate that sensory denervation facilitates the occurrence of BRONJ and that CGRP used therapeutically may prevent BRONJ progression, provided that SP is also present. Further studies are necessary to determine the optimal ratio of CGRP to SP for promoting bone healing and to uncover the mechanism by which CGRP and SP cooperate.<\/jats:p>","DOI":"10.1111\/nyas.14540","type":"journal-article","created":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T01:43:25Z","timestamp":1607651005000},"page":"56-73","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Sensory denervation increases potential of bisphosphonates to induce osteonecrosis via disproportionate expression of calcitonin gene\u2013related peptide and substance P"],"prefix":"10.1111","volume":"1487","author":[{"given":"Dongni","family":"Xie","sequence":"first","affiliation":[{"name":"Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Stomatological Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yamei","family":"Xu","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Stomatological Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yao","family":"Yang","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Stomatological Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyi","family":"Hua","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Stomatological Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oral Implantology Stomatological Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Oral Implantology Stomatological Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingqing","family":"Wu","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Stomatological Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,12,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-200101000-00003"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-007-0540-8"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-0843"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-43798-z"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joms.2009.03.005"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-016-0810-7"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ccr3.751"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2008.09.012"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01592.x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.735795"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2010.11.007"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01664"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-2391(96)90166-4"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-0825.2010.01677.x"},{"key":"e_1_2_9_16_1","first-page":"S76","article-title":"Alendronate transiently impairs removal of alveolar bone and healing of the root socket after tooth extraction in rats","volume":"23","author":"Aguirre J.I.","year":"2008","journal-title":"J. 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