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The pathogenesis of osteonecrosis has not been fully elucidated yet, and there is an unmet need for predictive biomarkers of bone complications. We aimed to assess the utility of angiogenesis and bone turnover biomarkers as predictors of osteonecrosis in Gaucher disease. Methods: Angiogenesis and bone turnover biomarkers were measured in 146 Gaucher disease patients (70M:76F, median age 49.5 [IQR 36.7 to 61]) with\/without osteonecrosis enrolled in the UK-based registry GAUCHERITE [enrolment 2015\u20132017]. Receiver-operating characteristic curve analysis was used to compare the osteonecrosis predictive value of angiogenesis and bone turnover biomarkers and determine the optimal cut-off values for each biomarker. Results: Sixty-two patients had osteonecrosis before study enrolment, 11 had osteonecrosis during follow-up, and 73 remained osteonecrosis-free. Patients with osteonecrosis showed increased osteopontin and matrix metalloproteinase (MMP)-2 levels and decreased MMP-9 and vascular endothelial growth factor (VEGF)-C compared with those free from osteonecrosis. MMP-9 predicted future osteonecrosis with higher sensitivity and specificity (area under the receiver operating characteristic curve [AUC] 0.84 [95% CI 0.84\u20130.99]; sensitivity\/specificity 82%\/75%; cutoff value \u2264 72,420 pg\/mL) than osteopontin, MMP-2 and VEGF-C when taken alone. The combination of MMP-9 and VEGF-C further increased the discriminating accuracy. Conclusions: The osteopontin\u2013MMPs\u2013VEGF axis is dysregulated in Gaucher disease patients with osteonecrosis. The combination of MMP-9 and VEGF-C circulating levels may serve to identify Gaucher disease patients at risk of osteonecrosis.<\/jats:p>","DOI":"10.3390\/metabo14110601","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T06:41:22Z","timestamp":1730961682000},"page":"601","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Changes in Angiogenesis and Bone Turnover Markers in Patients with Gaucher Disease Developing Osteonecrosis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5432-8808","authenticated-orcid":false,"given":"Simona","family":"D\u2019Amore","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK"},{"name":"Department of Precision and Regenerative Medicine\u2014Ionian Pole, School of Medicine, \u201cAldo Moro\u201d University of Bari, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth Eric","family":"Poole","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4703-7447","authenticated-orcid":false,"given":"Uma","family":"Ramaswami","sequence":"additional","affiliation":[{"name":"Lysosomal Storage Disorders Unit, Royal Free Hospital NHS Foundation Trust, London NW3 2QG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4531-9173","authenticated-orcid":false,"given":"Derralynn","family":"Hughes","sequence":"additional","affiliation":[{"name":"Lysosomal Storage Disorders Unit, Royal Free Hospital NHS Foundation Trust, London NW3 2QG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen","family":"Page","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2293-9698","authenticated-orcid":false,"given":"Antonio Giovanni","family":"Solimando","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine\u2014Ionian Pole, School of Medicine, \u201cAldo Moro\u201d University of Bari, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4567-8216","authenticated-orcid":false,"given":"Angelo","family":"Vacca","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine\u2014Ionian Pole, School of Medicine, \u201cAldo Moro\u201d University of Bari, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4951-9941","authenticated-orcid":false,"given":"Timothy Martin","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9427-9900","authenticated-orcid":false,"given":"Patrick","family":"Deegan","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s00109-021-02174-z","article-title":"Gaucher disease\u2014More than just a rare lipid storage disease","volume":"100","author":"Roh","year":"2022","journal-title":"J. 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Oncol."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/14\/11\/601\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:28:06Z","timestamp":1760113686000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/14\/11\/601"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,7]]},"references-count":52,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["metabo14110601"],"URL":"https:\/\/doi.org\/10.3390\/metabo14110601","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,7]]}}}