{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:11:20Z","timestamp":1791925880970,"version":"4.3.4"},"reference-count":64,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T00:00:00Z","timestamp":1686700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003336","name":"Bulgarian National Science Fund","doi-asserted-by":"publisher","award":["KP-06-N33\/9"],"award-info":[{"award-number":["KP-06-N33\/9"]}],"id":[{"id":"10.13039\/501100003336","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Subchondral bone that has intense communication with the articular cartilage might be a potential target for pharmacological treatment in the early stages of osteoarthritis (OA). Considering the emerging data about the role of adipokines in the pathogenesis of OA, the administration of drugs that influence their level is also intriguing. Metformin and alendronate were administered in mice with collagenase-induced OA (CIOA) as a monotherapy and in combination. Safranin O staining was used for the assessment of changes in subchondral bone and articular cartilage. Before and after treatment, serum levels of visfatin and biomarkers of cartilage turnover (CTX-II, MMP-13, and COMP) were assessed. In the current study, the combined administration of alendronate and metformin in mice with CIOA led to the protection against cartilage and subchondral bone damage. In mice with CIOA, metformin led to a decrease in visfatin level. In addition, treatment with metformin, alendronate, or their combination lowered the level of cartilage biomarkers (CTX-II and COMP), while the level of MMP-13 was not influenced. In conclusion, personalized combination treatment in OA according to clinical phenotype, especially in the early stages of the disease, might lead to the identification of a successful disease-modifying therapeutic protocol in OA.<\/jats:p>","DOI":"10.3390\/ijms241210103","type":"journal-article","created":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T02:01:40Z","timestamp":1686708100000},"page":"10103","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Changes in the Subchondral Bone, Visfatin, and Cartilage Biomarkers after Pharmacological Treatment of Experimental Osteoarthritis with Metformin and Alendronate"],"prefix":"10.3390","volume":"24","author":[{"given":"Sevdalina Nikolova","family":"Lambova","sequence":"first","affiliation":[{"name":"Department of Propaedeutics of Internal Diseases, Faculty of Medicine, Medical University\u2014Plovdiv, 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Ivanovska","sequence":"additional","affiliation":[{"name":"Department of Immunology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stela","family":"Stoyanova","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Paisii Hilendarski University of Plovdiv, 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyudmila","family":"Belenska-Todorova","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Sofia University \u201cSt. Kliment Ohridski\u201d, 1407 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elenka","family":"Georgieva","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Paisii Hilendarski University of Plovdiv, 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6560-1945","authenticated-orcid":false,"given":"Tsvetelina","family":"Batsalova","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Paisii Hilendarski University of Plovdiv, 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7998-5214","authenticated-orcid":false,"given":"Dzhemal","family":"Moten","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Paisii Hilendarski University of Plovdiv, 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desislava","family":"Apostolova","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Paisii Hilendarski University of Plovdiv, 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8052-5840","authenticated-orcid":false,"given":"Balik","family":"Dzhambazov","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Paisii Hilendarski University of Plovdiv, 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.joca.2021.10.003","article-title":"Osteoarthritis year in review 2021: Epidemiology & therapy","volume":"30","author":"Quicke","year":"2022","journal-title":"Osteoarthr. 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