{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T02:58:58Z","timestamp":1774321138374,"version":"3.50.1"},"reference-count":54,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T00:00:00Z","timestamp":1731283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008993","name":"Universiy of Zagreb","doi-asserted-by":"publisher","award":["10106-24-1503"],"award-info":[{"award-number":["10106-24-1503"]}],"id":[{"id":"10.13039\/100008993","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Introduction: Non-unions are fractures that do not heal properly, resulting in a false joint formation at the fracture site. This condition leads to major health issues and imposes a burden on national healthcare systems. The etiology of non-unions is still not fully understood; therefore, we aimed to identify potential systemic factors that may contribute to their formation. Materials and methods: We conducted a cross-sectional concomitant proteomic and metabolomic pilot study of blood plasma in patients with non-unions (N = 11) and compared them with patients with bone fracture in the normal active healing phase (N = 12). Results: We found five significantly upregulated proteins in the non-union group: immunoglobulin heavy variable 3\u201374, immunoglobulin lambda variable 2\u201318, low-density lipoprotein receptor-related protein 4, zinc-alpha-2-glycoprotein, and serum amyloid A-1 protein; and we found one downregulated protein: cystatin-C. The metabolomic study found differences in alanine, aspartate and glutamate metabolism pathways between two groups. Conclusions: The combined results of proteomic and metabolomic analyses suggest that the dysregulation of lipid metabolism may contribute to non-union formation.<\/jats:p>","DOI":"10.3390\/bioengineering11111135","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T03:52:07Z","timestamp":1731297127000},"page":"1135","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Systemic Lipid Metabolism Dysregulation as a Possible Driving Force of Fracture Non-Unions?"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9814-3178","authenticated-orcid":false,"given":"Lovorka","family":"Grgurevi\u0107","sequence":"first","affiliation":[{"name":"Center for Translational and Clinical Research, Department of Proteomics, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Anatomy, \u201cDrago Perovic\u201d, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"Biomedical Research Center Salata, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ru\u0111er","family":"Novak","sequence":"additional","affiliation":[{"name":"Center for Translational and Clinical Research, Department of Proteomics, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"Biomedical Research Center Salata, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucija","family":"Jambro\u0161i\u0107","sequence":"additional","affiliation":[{"name":"Center for Translational and Clinical Research, Department of Proteomics, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6537-9566","authenticated-orcid":false,"given":"Marko","family":"Mo\u010dibob","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5051-1843","authenticated-orcid":false,"given":"Morana","family":"Jaganjac","sequence":"additional","affiliation":[{"name":"Laboratory for Oxidative Stress, Division of Molecular Medicine, Ruder Boskovic Institute, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1715-1625","authenticated-orcid":false,"given":"Mirna","family":"Halasz","sequence":"additional","affiliation":[{"name":"Laboratory for Oxidative Stress, Division of Molecular Medicine, Ruder Boskovic Institute, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7782-1646","authenticated-orcid":false,"given":"Grgur","family":"Salai","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, University Hospital Dubrava, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stela","family":"Hrka\u010d","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Allergology and Rheumatology, University Hospital Dubrava, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9008-7645","authenticated-orcid":false,"given":"Milan","family":"Milo\u0161evi\u0107","sequence":"additional","affiliation":[{"name":"Department for Environmental and Occupational Health, Andrija Stampar School of Public Health, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomislav","family":"Vlahovi\u0107","sequence":"additional","affiliation":[{"name":"Clinic of Traumatology, University Hospital Center \u201cSestre Milosrdnice\u201d, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeronim","family":"Romi\u0107","sequence":"additional","affiliation":[{"name":"Clinic of Traumatology, University Hospital Center \u201cSestre Milosrdnice\u201d, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dra\u017een","family":"Mati\u010di\u0107","sequence":"additional","affiliation":[{"name":"Clinics for Surgery, Orthopedics and Ophthalmology, Faculty of Veterinary Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dinko","family":"Vidovi\u0107","sequence":"additional","affiliation":[{"name":"Clinic of Traumatology, University Hospital Center \u201cSestre Milosrdnice\u201d, 10000 Zagreb, Croatia"},{"name":"School of Dental Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Surgery, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bahney, C.S., Zondervan, R.L., Allison, P., Theologis, A., Ashley, J.W., Ahn, J., Miclau, T., Marcucio, R.S., and Hankenson, K.D. 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