{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T17:05:39Z","timestamp":1789491939694,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T00:00:00Z","timestamp":1722211200000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["esskajournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J. exp. orthop."],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To identify biomarkers in human blood or urine at an early stage of knee osteoarthritis (OA) and to elucidate if any can accurately differentiate between healthy controls and early knee OA patients and be considered as a candidate for widespread clinical use for early diagnosis of the disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Medline, Embase and Web of Science were screened to identify comparative studies measuring differences in blood or urine biomarkers between healthy controls and knee OA patients at an early stage (grade 1 or 2 Kellgren\u2013Laurence). Two independent reviewers screened the abstracts for eligibility, reviewed the full texts, assessed the methodological quality and extracted the data. The Joanna Briggs Institute critical appraisal tool for diagnostic test accuracy studies was used to assess the quality of the included studies. Due to relevant heterogeneity, meta\u2010analysis was not appropriate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Five studies met the eligibility criteria. The examined biomarkers were adropin, collagen type II metabolite, C\u2010terminal cross\u2010linked telopeptide of type II collagen, C\u2010terminal cross\u2010linked telopeptide of type I collagen, cartilage oligomeric matrix protein, matrix metalloproteinase 3, N\u2010terminal propeptide of procollagen type IIA, type I procollagen N\u2010terminal propeptides, N\u2010terminal osteocalcin, angiopoietin\u20102, follistatin, granulocyte colony\u2010stimulating factor, hepatocyte growth factor, interleukin\u20108, leptin, platelet\u2010derived growth factor\u2010BB, platelet endothelial cell adhesion molecule\u20101, vascular endothelial growth factor and calprotectin and totalling 19 biomarkers. All of the biomarkers were studied only once in the selected papers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>There is no reliable biomarker available to differentiate between early knee OA in patients and healthy controls, but a potential role of a cluster of biomarkers to close this gap. There are several limitations, including inappropriate study designs, small sample sizes, nonconsecutive patient groups and inadequate statistical methods for evaluating biomarker performance in studies included.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Level of Evidence<\/jats:title>\n                    <jats:p>Level III.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jeo2.12105","type":"journal-article","created":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T09:16:28Z","timestamp":1722244588000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Blood and urine biomarkers for the diagnosis of early stages of knee osteoarthritis: A systematic review"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0108-5750","authenticated-orcid":false,"given":"Marko","family":"Ostojic","sequence":"first","affiliation":[{"name":"Department of Orthopaedics and Traumatology University Hospital Mostar Mostar Bosnia and Herzegovina"},{"name":"Osteon Orthopedics Trauma and Sports Medicine Clinic Mostar Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6813-043X","authenticated-orcid":false,"given":"Joao Pedro","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Coimbra Coimbra Portugal"},{"name":"Orthopaedic Department, Hospitais da Universidade de Coimbra Unidade Local de Sa\u00fade de Coimbra Coimbra Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Kordic","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Traumatology 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