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Over the past few years, several studies have demonstrated that bone and the surrounding muscle tissue interact not only anatomically and mechanically but also through biochemical pathways and mediators. Severe damage to the surrounding musculature at the fracture site causes an insufficiency in muscle\u2010derived osteoprogenitor cells that are crucial for fracture healing. As an endocrine tissue, skeletal muscle produces many myokines that act on different bone cells, such as osteoblasts, osteoclasts, osteocytes, and mesenchymal stem cells. Investigating how muscle influences fracture healing at cellular, molecular, and hormonal levels provides translational therapeutic solutions to this clinical challenge. This review provides an overview about the contributions of surrounding muscle tissue in directing fracture healing. The focus of the review is on describing the interactions between bone and muscle in both healthy and fractured environments. We discuss current progress in identifying the bone\u2013muscle molecular pathways and strategies to harness these pathways as cues for accelerating fracture healing. In addition, we review the existing challenges and research opportunities in the field.<\/jats:p>","DOI":"10.1002\/jor.25746","type":"journal-article","created":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T14:15:42Z","timestamp":1700662542000},"page":"249-258","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The critical impact of traumatic muscle loss on fracture healing: Basic science and clinical aspects"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5089-8693","authenticated-orcid":false,"given":"Maryam","family":"Rahmati","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery University of California, Davis Sacramento California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Haffner","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of California, Davis Sacramento California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of California, Davis Sacramento California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan Kent","family":"Leach","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of California, Davis Sacramento California USA"},{"name":"Department of Biomedical Engineering University of California, Davis Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augustine M.","family":"Saiz","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of California, Davis Sacramento California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,29]]},"reference":[{"key":"e_1_2_3_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamasurg.2016.2775"},{"key":"e_1_2_3_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/1460408615591625"},{"key":"e_1_2_3_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11657-020-0706-y"},{"key":"e_1_2_3_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00104-015-0050-8"},{"key":"e_1_2_3_6_1","doi-asserted-by":"publisher","DOI":"10.5435\/00124635-201102000-00003"},{"key":"e_1_2_3_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005373-198408000-00009"},{"key":"e_1_2_3_8_1","first-page":"1","article-title":"Muscle\u2010bone interactions during fracture healing","volume":"15","author":"Davis KM","year":"2015","journal-title":"J Musculoskelet Neuronal Interact"},{"key":"e_1_2_3_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/joor.12747"},{"key":"e_1_2_3_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9010071"},{"key":"e_1_2_3_11_1","doi-asserted-by":"publisher","DOI":"10.3233\/SHTI280"},{"key":"e_1_2_3_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-19438-4"},{"key":"e_1_2_3_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2023.116833"},{"key":"e_1_2_3_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2389"},{"key":"e_1_2_3_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-018-4570-1"},{"key":"e_1_2_3_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2019.05.018"},{"key":"e_1_2_3_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21041178"},{"key":"e_1_2_3_18_1","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-199072020-00023"},{"key":"e_1_2_3_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00423-003-0379-1"},{"key":"e_1_2_3_20_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.G.01192"},{"key":"e_1_2_3_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2011.12.007"},{"key":"e_1_2_3_22_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tec.2012.0290"},{"key":"e_1_2_3_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.21553"},{"key":"e_1_2_3_24_1","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.88B3.16465"},{"key":"e_1_2_3_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa012604"},{"key":"e_1_2_3_26_1","doi-asserted-by":"publisher","DOI":"10.3928\/01477447-20100722-02"},{"key":"e_1_2_3_27_1","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-199310000-00003"},{"key":"e_1_2_3_28_1","first-page":"1801","article-title":"Long\u2010term persistence of disability following severe lower\u2010limb trauma. 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