{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:50:49Z","timestamp":1787028649351,"version":"build-2736575974"},"reference-count":51,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T00:00:00Z","timestamp":1713312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["5xMille 2020"],"award-info":[{"award-number":["5xMille 2020"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["7333288"],"award-info":[{"award-number":["7333288"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"name":"IRCCS Istituto Ortopedico Rizzoli (Ricerca Corrente)","award":["5xMille 2020"],"award-info":[{"award-number":["5xMille 2020"]}]},{"name":"IRCCS Istituto Ortopedico Rizzoli (Ricerca Corrente)","award":["7333288"],"award-info":[{"award-number":["7333288"]}]},{"name":"H2020 ORTHOUNION Project","award":["5xMille 2020"],"award-info":[{"award-number":["5xMille 2020"]}]},{"name":"H2020 ORTHOUNION Project","award":["7333288"],"award-info":[{"award-number":["7333288"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Fracture healing is a very complex and well-orchestrated regenerative process involving many cell types and molecular pathways. Despite the high efficiency of this process, unsatisfying healing outcomes, such as non-union, occur for approximately 5\u201310% of long bone fractures. Although there is an obvious need to identify markers to monitor the healing process and to predict a potential failure in callus formation to heal the fracture, circulating bone turnover markers\u2019 (BTMs) utility as biomarkers in association with radiographic and clinical examination still lacks evidence so far. Methods: A systematic review on the association between BTMs changes and fracture healing in long bone non-union was performed following PRISMA guidelines. The research papers were identified via the PubMed, Cochrane, Cinahl, Web of Science, Scopus, and Embase databases. Studies in which the failure of fracture healing was associated with osteoporosis or genetic disorders were not included. Results: A total of 172 studies were collected and, given the inclusion criteria, 14 manuscripts were included in this review. Changes in circulating BTMs levels were detected during the healing process and across groups (healed vs. non-union patients and healthy vs. patients with non-union). However, we found high heterogeneity in patients\u2019 characteristics (fracture site, gender, and age) and in sample scheduling, which made it impossible to perform a meta-analysis. Conclusions: Clinical findings and radiographic features remain the two important components of non-union diagnosis so far. We suggest improving blood sample standardization and clinical data collection in future research to lay the foundations for the effective use of BTMs as tools for diagnosing non-union.<\/jats:p>","DOI":"10.3390\/jcm13082333","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T06:21:12Z","timestamp":1713421272000},"page":"2333","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Association between Bone Turnover Markers and Fracture Healing in Long Bone Non-Union: A Systematic Review"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3783-7803","authenticated-orcid":false,"given":"Francesca","family":"Perut","sequence":"first","affiliation":[{"name":"Biomedical Science and Technologies and Nanobiotechnology Laboratory, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5437-6543","authenticated-orcid":false,"given":"Laura","family":"Roncuzzi","sequence":"additional","affiliation":[{"name":"Biomedical Science and Technologies and Nanobiotechnology Laboratory, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1065-6137","authenticated-orcid":false,"given":"Enrique","family":"G\u00f3mez-Barrena","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery and Traumatology, Hospital Universitario La Paz-IdiPAZ, 28046 Madrid, Spain"},{"name":"Facultad de Medicina, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Baldini","sequence":"additional","affiliation":[{"name":"Biomedical Science and Technologies and Nanobiotechnology Laboratory, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"},{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.1007\/s11999-008-0416-z","article-title":"The Global Burden of Musculoskeletal Injuries: Challenges and Solutions","volume":"466","author":"Mock","year":"2008","journal-title":"Clin. 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