{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T06:05:45Z","timestamp":1784354745698,"version":"3.55.0"},"reference-count":84,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Inflammopharmacol"],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1007\/s10787-025-01902-y","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T16:00:25Z","timestamp":1758816025000},"page":"5963-5975","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Update on metformin for osteoarthritis treatment"],"prefix":"10.1007","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6742-1428","authenticated-orcid":false,"given":"Ben-Zheng","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He-Xin","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-zhi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Ze","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An-Ren","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1429-8683","authenticated-orcid":false,"given":"Hong-Zhang","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"issue":"1","key":"1902_CR1","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s13075-023-03025-7","volume":"25","author":"N Alimoradi","year":"2023","unstructured":"Alimoradi N, Tahami M, Firouzabadi N, Haem E, Ramezani A (2023) Metformin attenuates symptoms of osteoarthritis: role of genetic diversity of Bcl2 and Cxcl16 in Oa. Arthritis Res Ther 25(1):35. https:\/\/doi.org\/10.1186\/s13075-023-03025-7","journal-title":"Arthritis Res Ther"},{"issue":"2","key":"1902_CR2","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.joca.2021.04.020","volume":"30","author":"KD Allen","year":"2022","unstructured":"Allen KD, Thoma LM, Golightly YM (2022) Epidemiology of osteoarthritis. Osteoarthr Cartil 30(2):184\u2013195. https:\/\/doi.org\/10.1016\/j.joca.2021.04.020","journal-title":"Osteoarthr Cartil"},{"issue":"3","key":"1902_CR3","doi-asserted-by":"publisher","first-page":"R97","DOI":"10.1530\/joe-15-0447","volume":"228","author":"H An","year":"2016","unstructured":"An H, He L (2016) Current understanding of metformin effect on the control of hyperglycemia in diabetes. J Endocrinol 228(3):R97-106. https:\/\/doi.org\/10.1530\/joe-15-0447","journal-title":"J Endocrinol"},{"issue":"9","key":"1902_CR4","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.1007\/s00125-017-4318-z","volume":"60","author":"CJ Bailey","year":"2017","unstructured":"Bailey CJ (2017) Metformin: historical overview. Diabetologia 60(9):1566\u20131576. https:\/\/doi.org\/10.1007\/s00125-017-4318-z","journal-title":"Diabetologia"},{"issue":"3","key":"1902_CR5","doi-asserted-by":"publisher","first-page":"e233646","DOI":"10.1001\/jamanetworkopen.2023.3646","volume":"6","author":"MC Baker","year":"2023","unstructured":"Baker MC, Sheth K, Liu Y, Lu D, Lu R, Robinson WH (2023) Development of osteoarthritis in adults with type 2 diabetes treated with metformin vs a sulfonylurea. JAMA Netw Open 6(3):e233646. https:\/\/doi.org\/10.1001\/jamanetworkopen.2023.3646","journal-title":"JAMA Netw Open"},{"issue":"11","key":"1902_CR6","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1016\/j.joca.2019.06.011","volume":"27","author":"RR Bannuru","year":"2019","unstructured":"Bannuru RR, Osani MC, Vaysbrot EE, Arden NK, Bennell K, Bierma-Zeinstra SMA, Kraus VB, Lohmander LS, Abbott JH, Bhandari M, Blanco FJ, Espinosa R, Haugen IK, Lin J, Mandl LA, Moilanen E, Nakamura N, Snyder-Mackler L, Trojian T, Underwood M, McAlindon TE (2019) Oarsi Guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthr Cartil 27(11):1578\u20131589. https:\/\/doi.org\/10.1016\/j.joca.2019.06.011","journal-title":"Osteoarthr Cartil"},{"issue":"4","key":"1902_CR7","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/j.joca.2021.06.013","volume":"30","author":"A Batushansky","year":"2022","unstructured":"Batushansky A, Zhu S, Komaravolu RK, South S, Mehta-D\u2019souza P, Griffin TM (2022) Fundamentals of Oa. an initiative of osteoarthritis and cartilage. Obesity and metabolic factors in Oa. Osteoarthr Cartil 30(4):501\u2013515. https:\/\/doi.org\/10.1016\/j.joca.2021.06.013","journal-title":"Osteoarthr Cartil"},{"issue":"3","key":"1902_CR8","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/j.apmr.2021.07.801","volume":"103","author":"D Bichsel","year":"2022","unstructured":"Bichsel D, Liechti FD, Schlapbach JM, Wertli MM (2022) Cross-sectional analysis of recommendations for the treatment of hip and knee osteoarthritis in clinical guidelines. Arch Phys Med Rehabil 103(3):559\u201369.e5. https:\/\/doi.org\/10.1016\/j.apmr.2021.07.801","journal-title":"Arch Phys Med Rehabil"},{"issue":"42","key":"1902_CR9","first-page":"V06200477","volume":"182","author":"H Bliddal","year":"2020","unstructured":"Bliddal H (2020) Definition, pathology and pathogenesis of osteoarthritis. Ugeskr Laeger 182(42):V06200477","journal-title":"Ugeskr Laeger"},{"issue":"5","key":"1902_CR10","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1038\/s41574-019-0176-8","volume":"15","author":"M Bl\u00fcher","year":"2019","unstructured":"Bl\u00fcher M (2019) Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol 15(5):288\u2013298. https:\/\/doi.org\/10.1038\/s41574-019-0176-8","journal-title":"Nat Rev Endocrinol"},{"issue":"1s","key":"1902_CR11","doi-asserted-by":"publisher","first-page":"S41","DOI":"10.1016\/j.otsr.2017.04.017","volume":"104","author":"F Canovas","year":"2018","unstructured":"Canovas F, Dagneaux L (2018) Quality of life after total knee arthroplasty. Orthop Traumatol Surg Res 104(1s):S41\u2013S46. https:\/\/doi.org\/10.1016\/j.otsr.2017.04.017","journal-title":"Orthop Traumatol Surg Res"},{"issue":"1","key":"1902_CR12","doi-asserted-by":"publisher","first-page":"1636","DOI":"10.1080\/07853890.2022.2085883","volume":"54","author":"Z Cao","year":"2022","unstructured":"Cao Z, Wu Y, Li Q, Li Y, Wu J (2022) A causal relationship between childhood obesity and risk of osteoarthritis: results from a two-sample Mendelian randomization analysis. Ann Med 54(1):1636\u20131645. https:\/\/doi.org\/10.1080\/07853890.2022.2085883","journal-title":"Ann Med"},{"key":"1902_CR13","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11164796","author":"S Chen","year":"2022","unstructured":"Chen S, Ruan G, Zeng M, Chen T, Cao P, Zhang Y, Li J, Wang X, Li S, Tang S, Lu S, Fan T, Li Y, Han W, Tan J, Ding C, Zhu Z (2022) Association between metformin use and risk of total knee arthroplasty and degree of knee pain in knee osteoarthritis patients with diabetes and\/or obesity: a retrospective study. J Clin Med. https:\/\/doi.org\/10.3390\/jcm11164796","journal-title":"J Clin Med"},{"issue":"12","key":"1902_CR14","doi-asserted-by":"publisher","first-page":"1743","DOI":"10.1002\/acr.22897","volume":"68","author":"BR Deshpande","year":"2016","unstructured":"Deshpande BR, Katz JN, Solomon DH, Yelin EH, Hunter DJ, Messier SP, Suter LG, Losina E (2016) Number of persons with symptomatic knee osteoarthritis in the us: impact of race and ethnicity, age, sex, and obesity. Arthritis Care Res (Hoboken) 68(12):1743\u20131750. https:\/\/doi.org\/10.1002\/acr.22897","journal-title":"Arthritis Care Res (Hoboken)"},{"issue":"2","key":"1902_CR15","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1378\/chest.118.2.503","volume":"118","author":"CA Dinarello","year":"2000","unstructured":"Dinarello CA (2000) Proinflammatory cytokines. Chest 118(2):503\u2013508. https:\/\/doi.org\/10.1378\/chest.118.2.503","journal-title":"Chest"},{"issue":"5","key":"1902_CR16","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","volume":"149","author":"SJ Dixon","year":"2012","unstructured":"Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, Morrison B 3rd, Stockwell BR (2012) Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149(5):1060\u20131072. https:\/\/doi.org\/10.1016\/j.cell.2012.03.042","journal-title":"Cell"},{"issue":"9","key":"1902_CR17","doi-asserted-by":"publisher","first-page":"2213","DOI":"10.1111\/os.13809","volume":"15","author":"X Du","year":"2023","unstructured":"Du X, Liu ZY, Tao XX, Mei YL, Zhou DQ, Cheng K, Gao SL, Shi HY, Song C, Zhang XM (2023) Research progress on the pathogenesis of knee osteoarthritis. Orthop Surg 15(9):2213\u20132224. https:\/\/doi.org\/10.1111\/os.13809","journal-title":"Orthop Surg"},{"issue":"23","key":"1902_CR18","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.21037\/atm-20-3042","volume":"8","author":"KJ Fan","year":"2020","unstructured":"Fan KJ, Wu J, Wang QS, Xu BX, Zhao FT, Wang TY (2020) Metformin inhibits inflammation and bone destruction in collagen-induced arthritis in rats. Ann Transl Med 8(23):1565. https:\/\/doi.org\/10.21037\/atm-20-3042","journal-title":"Ann Transl Med"},{"issue":"2","key":"1902_CR19","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.18632\/aging.102635","volume":"12","author":"X Feng","year":"2020","unstructured":"Feng X, Pan J, Li J, Zeng C, Qi W, Shao Y, Liu X, Liu L, Xiao G, Zhang H, Bai X, Cai D (2020) Metformin attenuates cartilage degeneration in an experimental osteoarthritis model by regulating Ampk\/Mtor. Aging (Albany NY) 12(2):1087\u20131103. https:\/\/doi.org\/10.18632\/aging.102635","journal-title":"Aging (Albany NY)"},{"issue":"19","key":"1902_CR20","doi-asserted-by":"publisher","first-page":"1926","DOI":"10.1001\/jama.2019.3805","volume":"321","author":"J Flory","year":"2019","unstructured":"Flory J, Lipska K (2019) Metformin in 2019. JAMA 321(19):1926\u20131927. https:\/\/doi.org\/10.1001\/jama.2019.3805","journal-title":"JAMA"},{"issue":"10","key":"1902_CR21","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1038\/s41574-019-0242-2","volume":"15","author":"M Foretz","year":"2019","unstructured":"Foretz M, Guigas B, Viollet B (2019) Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus. Nat Rev Endocrinol 15(10):569\u2013589. https:\/\/doi.org\/10.1038\/s41574-019-0242-2","journal-title":"Nat Rev Endocrinol"},{"issue":"8","key":"1902_CR22","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1038\/s41574-023-00833-4","volume":"19","author":"M Foretz","year":"2023","unstructured":"Foretz M, Guigas B, Viollet B (2023) Metformin: update on mechanisms of action and repurposing potential. Nat Rev Endocrinol 19(8):460\u2013476. https:\/\/doi.org\/10.1038\/s41574-023-00833-4","journal-title":"Nat Rev Endocrinol"},{"issue":"1","key":"1902_CR23","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.jacc.2017.11.011","volume":"71","author":"KM Gadde","year":"2018","unstructured":"Gadde KM, Martin CK, Berthoud HR, Heymsfield SB (2018) Obesity: pathophysiology and management. J Am Coll Cardiol 71(1):69\u201384. https:\/\/doi.org\/10.1016\/j.jacc.2017.11.011","journal-title":"J Am Coll Cardiol"},{"issue":"6","key":"1902_CR24","first-page":"537","volume":"115","author":"GR Galakatos","year":"2018","unstructured":"Galakatos GR (2018) Direct anterior total hip arthroplasty. Mo Med 115(6):537\u2013541","journal-title":"Mo Med"},{"key":"1902_CR25","doi-asserted-by":"publisher","first-page":"155043","DOI":"10.1016\/j.cyto.2020.155043","volume":"129","author":"YH Gao","year":"2020","unstructured":"Gao YH, Zhao CW, Liu B, Dong N, Ding L, Li YR, Liu JG, Feng W, Qi X, Jin XH (2020) An update on the association between metabolic syndrome and osteoarthritis and on the potential role of leptin in osteoarthritis. Cytokine 129:155043. https:\/\/doi.org\/10.1016\/j.cyto.2020.155043","journal-title":"Cytokine"},{"key":"1902_CR26","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24076405","author":"R Giorgino","year":"2023","unstructured":"Giorgino R, Albano D, Fusco S, Peretti GM, Mangiavini L, Messina C (2023) Knee osteoarthritis: epidemiology, pathogenesis, and mesenchymal stem cells: what else is new? An update. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms24076405","journal-title":"Int J Mol Sci"},{"issue":"9991","key":"1902_CR27","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1016\/s0140-6736(14)60802-3","volume":"386","author":"S Glyn-Jones","year":"2015","unstructured":"Glyn-Jones S, Palmer AJ, Agricola R, Price AJ, Vincent TL, Weinans H, Carr AJ (2015) Osteoarthritis. Lancet 386(9991):376\u2013387. https:\/\/doi.org\/10.1016\/s0140-6736(14)60802-3","journal-title":"Lancet"},{"issue":"12","key":"1902_CR28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0261127","volume":"16","author":"H Guo","year":"2021","unstructured":"Guo H, Ding D, Wang L, Yan J, Ma L, Jin Q (2021) Metformin attenuates osteoclast-mediated abnormal subchondral bone remodeling and alleviates osteoarthritis via Ampk\/Nf-\u039ab\/Erk signaling pathway. PLoS ONE 16(12):e0261127. https:\/\/doi.org\/10.1371\/journal.pone.0261127","journal-title":"PLoS ONE"},{"key":"1902_CR29","doi-asserted-by":"publisher","DOI":"10.3390\/cells11193012","author":"M He","year":"2022","unstructured":"He M, Lu B, Opoku M, Zhang L, Xie W, Jin H, Chen S, Li Y, Deng Z (2022) Metformin prevents or delays the development and progression of osteoarthritis: new insight and mechanism of action. Cells. https:\/\/doi.org\/10.3390\/cells11193012","journal-title":"Cells"},{"issue":"10","key":"1902_CR30","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1007\/s40265-015-0416-8","volume":"75","author":"U Hostalek","year":"2015","unstructured":"Hostalek U, Gwilt M, Hildemann S (2015) Therapeutic use of metformin in prediabetes and diabetes prevention. Drugs 75(10):1071\u20131094. https:\/\/doi.org\/10.1007\/s40265-015-0416-8","journal-title":"Drugs"},{"issue":"10182","key":"1902_CR31","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1016\/s0140-6736(19)30417-9","volume":"393","author":"DJ Hunter","year":"2019","unstructured":"Hunter DJ, Bierma-Zeinstra S (2019) Osteoarthritis. Lancet 393(10182):1745\u20131759. https:\/\/doi.org\/10.1016\/s0140-6736(19)30417-9","journal-title":"Lancet"},{"issue":"6","key":"1902_CR32","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1038\/nrrheum.2017.53","volume":"13","author":"A Ioan-Facsinay","year":"2017","unstructured":"Ioan-Facsinay A, Kloppenburg M (2017) Osteoarthritis: inflammation and fibrosis in adipose tissue of osteoarthritic joints. Nat Rev Rheumatol 13(6):325\u2013326. https:\/\/doi.org\/10.1038\/nrrheum.2017.53","journal-title":"Nat Rev Rheumatol"},{"key":"1902_CR33","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22052619","author":"S Jang","year":"2021","unstructured":"Jang S, Lee K, Ju JH (2021) Recent updates of diagnosis, pathophysiology, and treatment on osteoarthritis of the knee. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms22052619","journal-title":"Int J Mol Sci"},{"issue":"4","key":"1902_CR34","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1038\/s41580-020-00324-8","volume":"22","author":"X Jiang","year":"2021","unstructured":"Jiang X, Stockwell BR, Conrad M (2021) Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol 22(4):266\u2013282. https:\/\/doi.org\/10.1038\/s41580-020-00324-8","journal-title":"Nat Rev Mol Cell Biol"},{"key":"1902_CR35","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/978-3-319-76735-2_3","volume":"1059","author":"G Jim\u00e9nez","year":"2018","unstructured":"Jim\u00e9nez G, Cobo-Molinos J, Antich C, L\u00f3pez-Ruiz E (2018) Osteoarthritis: trauma vs disease. Adv Exp Med Biol 1059:63\u201383. https:\/\/doi.org\/10.1007\/978-3-319-76735-2_3","journal-title":"Adv Exp Med Biol"},{"issue":"3","key":"1902_CR36","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1001\/jama.2016.17822","volume":"317","author":"J Jin","year":"2017","unstructured":"Jin J (2017) Stem cell treatments. JAMA 317(3):330. https:\/\/doi.org\/10.1001\/jama.2016.17822","journal-title":"JAMA"},{"issue":"2","key":"1902_CR37","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1038\/s41584-018-0123-4","volume":"15","author":"IA Jones","year":"2019","unstructured":"Jones IA, Togashi R, Wilson ML, Heckmann N, Vangsness CT Jr. (2019) Intra-articular treatment options for knee osteoarthritis. Nat Rev Rheumatol 15(2):77\u201390. https:\/\/doi.org\/10.1038\/s41584-018-0123-4","journal-title":"Nat Rev Rheumatol"},{"issue":"2","key":"1902_CR38","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1002\/art.41142","volume":"72","author":"SL Kolasinski","year":"2020","unstructured":"Kolasinski SL, Neogi T, Hochberg MC, Oatis C, Guyatt G, Block J, Callahan L, Copenhaver C, Dodge C, Felson D, Gellar K, Harvey WF, Hawker G, Herzig E, Kwoh CK, Nelson AE, Samuels J, Scanzello C, White D, Wise B, Altman RD, DiRenzo D, Fontanarosa J, Giradi G, Ishimori M, Misra D, Shah AA, Shmagel AK, Thoma LM, Turgunbaev M, Turner AS, Reston J (2020) 2019 American college of rheumatology\/arthritis foundation guideline for the management of osteoarthritis of the hand, hip, and knee. Arthritis Rheumatol 72(2):220\u2013233. https:\/\/doi.org\/10.1002\/art.41142","journal-title":"Arthritis Rheumatol"},{"issue":"1","key":"1902_CR39","doi-asserted-by":"publisher","first-page":"11571","DOI":"10.1038\/s41598-022-15871-7","volume":"12","author":"FTT Lai","year":"2022","unstructured":"Lai FTT, Yip BHK, Hunter DJ, Rabago DP, Mallen CD, Yeoh EK, Wong SYS, Sit RW (2022) Metformin use and the risk of total knee replacement among diabetic patients: a propensity-score-matched retrospective cohort study. Sci Rep 12(1):11571. https:\/\/doi.org\/10.1038\/s41598-022-15871-7","journal-title":"Sci Rep"},{"key":"1902_CR40","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241210103","author":"SN Lambova","year":"2023","unstructured":"Lambova SN, Ivanovska N, Stoyanova S, Belenska-Todorova L, Georgieva E, Batsalova T, Moten D, Apostolova D, Dzhambazov B (2023) Changes in the subchondral bone, visfatin, and cartilage biomarkers after pharmacological treatment of experimental osteoarthritis with metformin and alendronate. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms241210103","journal-title":"Int J Mol Sci"},{"issue":"1","key":"1902_CR41","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1210\/endrev\/bnaa023","volume":"42","author":"TE LaMoia","year":"2021","unstructured":"LaMoia TE, Shulman GI (2021) Cellular and molecular mechanisms of metformin action. Endocr Rev 42(1):77\u201396. https:\/\/doi.org\/10.1210\/endrev\/bnaa023","journal-title":"Endocr Rev"},{"issue":"1","key":"1902_CR42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s43019-022-00132-8","volume":"34","author":"DH Lee","year":"2022","unstructured":"Lee DH, Kim SJ, Kim SA, Ju GI (2022) Past, present, and future of cartilage restoration: from localized defect to arthritis. Knee Surg Relat Res 34(1):1. https:\/\/doi.org\/10.1186\/s43019-022-00132-8","journal-title":"Knee Surg Relat Res"},{"key":"1902_CR43","doi-asserted-by":"publisher","DOI":"10.1172\/jci141008","author":"A Levescot","year":"2021","unstructured":"Levescot A, Chang MH, Schnell J, Nelson-Maney N, Yan J, Mart\u00ednez-Bonet M, Grieshaber-Bouyer R, Lee PY, Wei K, Blaustein RB, Morris A, Wactor A, Iwakura Y, Lederer JA, Rao DA, Charles JF, Nigrovic PA (2021) Il-1\u03b2-driven osteoclastogenic Tregs accelerate bone erosion in arthritis. J Clin Invest. https:\/\/doi.org\/10.1172\/jci141008","journal-title":"J Clin Invest"},{"key":"1902_CR44","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.00304","volume":"7","author":"D Li","year":"2020","unstructured":"Li D, Li S, Chen Q, Xie X (2020a) The prevalence of symptomatic knee osteoarthritis in relation to age, sex, area, region, and body mass index in China: a systematic review and meta-analysis. Front Med 7:304. https:\/\/doi.org\/10.3389\/fmed.2020.00304","journal-title":"Front Med"},{"issue":"1","key":"1902_CR45","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s13075-020-2129-y","volume":"22","author":"H Li","year":"2020","unstructured":"Li H, Ding X, Terkeltaub R, Lin H, Zhang Y, Zhou B, He K, Li K, Liu Z, Wei J, Yang Y, Xie H, Zeng C, Lei G (2020b) Exploration of metformin as novel therapy for osteoarthritis: preventing cartilage degeneration and reducing pain behavior. Arthritis Res Ther 22(1):34. https:\/\/doi.org\/10.1186\/s13075-020-2129-y","journal-title":"Arthritis Res Ther"},{"issue":"5","key":"1902_CR46","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1136\/annrheumdis-2019-216713","volume":"79","author":"J Li","year":"2020","unstructured":"Li J, Zhang B, Liu WX, Lu K, Pan H, Wang T, Oh CD, Yi D, Huang J, Zhao L, Ning G, Xing C, Xiao G, Liu-Bryan R, Feng S, Chen D (2020c) Metformin limits osteoarthritis development and progression through activation of Ampk signalling. Ann Rheum Dis 79(5):635\u2013645. https:\/\/doi.org\/10.1136\/annrheumdis-2019-216713","journal-title":"Ann Rheum Dis"},{"issue":"4","key":"1902_CR47","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.1093\/rheumatology\/keac467","volume":"62","author":"D Li","year":"2023","unstructured":"Li D, Ruan G, Zhang Y, Zhao Y, Zhu Z, Ou Q, Huang H, Chen J, Han W, Tang S, Li J, Wang L, Chen T, Bai X, Cai D, Ding C (2023) Metformin attenuates osteoarthritis by targeting chondrocytes, synovial macrophages and adipocytes. Rheumatology (Oxford) 62(4):1652\u20131661. https:\/\/doi.org\/10.1093\/rheumatology\/keac467","journal-title":"Rheumatology (Oxford)"},{"issue":"11","key":"1902_CR48","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1016\/j.joca.2022.05.005","volume":"30","author":"YZ Lim","year":"2022","unstructured":"Lim YZ, Wang Y, Estee M, Abidi J, Kumar MU, Hussain SM, Wluka AE, Little CB, Cicuttini FM (2022) Metformin as a potential disease-modifying drug in osteoarthritis: a systematic review of pre-clinical and human studies. Osteoarthr Cartil 30(11):1434\u20131442. https:\/\/doi.org\/10.1016\/j.joca.2022.05.005","journal-title":"Osteoarthr Cartil"},{"key":"1902_CR49","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1093\/bmb\/lds038","volume":"105","author":"A Litwic","year":"2013","unstructured":"Litwic A, Edwards MH, Dennison EM, Cooper C (2013) Epidemiology and burden of osteoarthritis. Br Med Bull 105:185\u2013199. https:\/\/doi.org\/10.1093\/bmb\/lds038","journal-title":"Br Med Bull"},{"issue":"7","key":"1902_CR50","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1038\/nrrheum.2016.65","volume":"12","author":"RF Loeser","year":"2016","unstructured":"Loeser RF, Collins JA, Diekman BO (2016) Ageing and the pathogenesis of osteoarthritis. Nat Rev Rheumatol 12(7):412\u2013420. https:\/\/doi.org\/10.1038\/nrrheum.2016.65","journal-title":"Nat Rev Rheumatol"},{"issue":"1","key":"1902_CR51","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0191242","volume":"13","author":"CH Lu","year":"2018","unstructured":"Lu CH, Chung CH, Lee CH, Hsieh CH, Hung YJ, Lin FH, Tsao CH, Hsieh PS, Chien WC (2018) Combination Cox-2 inhibitor and metformin attenuate rate of joint replacement in osteoarthritis with diabetes: a nationwide, retrospective, matched-cohort study in Taiwan. PLoS ONE 13(1):e0191242. https:\/\/doi.org\/10.1371\/journal.pone.0191242","journal-title":"PLoS ONE"},{"issue":"9","key":"1902_CR52","doi-asserted-by":"publisher","first-page":"152","DOI":"10.3238\/arztebl.2010.0152","volume":"107","author":"JW Michael","year":"2010","unstructured":"Michael JW, Schl\u00fcter-Brust KU, Eysel P (2010) The epidemiology, etiology, diagnosis, and treatment of osteoarthritis of the knee. Dtsch Arztebl Int 107(9):152\u2013162. https:\/\/doi.org\/10.3238\/arztebl.2010.0152","journal-title":"Dtsch Arztebl Int"},{"issue":"2","key":"1902_CR53","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1002\/art.40692","volume":"71","author":"D Misra","year":"2019","unstructured":"Misra D, Fielding RA, Felson DT, Niu J, Brown C, Nevitt M, Lewis CE, Torner J, Neogi T (2019) Risk of knee osteoarthritis with obesity, sarcopenic obesity, and sarcopenia. Arthritis Rheumatol 71(2):232\u2013237. https:\/\/doi.org\/10.1002\/art.40692","journal-title":"Arthritis Rheumatol"},{"key":"1902_CR54","doi-asserted-by":"publisher","DOI":"10.3390\/cells10030681","author":"HS Na","year":"2021","unstructured":"Na HS, Kwon JY, Lee SY, Lee SH, Lee AR, Woo JS, Jung K, Cho KH, Choi JW, Lee DH, Min HK, Park SH, Kim SJ, Cho ML (2021) Metformin attenuates monosodium-iodoacetate-induced osteoarthritis via regulation of pain mediators and the autophagy-lysosomal pathway. Cells. https:\/\/doi.org\/10.3390\/cells10030681","journal-title":"Cells"},{"key":"1902_CR55","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.907750","volume":"13","author":"U Nedunchezhiyan","year":"2022","unstructured":"Nedunchezhiyan U, Varughese I, Sun AR, Wu X, Crawford R, Prasadam I (2022) Obesity, inflammation, and immune system in osteoarthritis. Front Immunol 13:907750. https:\/\/doi.org\/10.3389\/fimmu.2022.907750","journal-title":"Front Immunol"},{"issue":"4","key":"1902_CR56","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1080\/14728214.2018.1547706","volume":"23","author":"WM Oo","year":"2018","unstructured":"Oo WM, Yu SP, Daniel MS, Hunter DJ (2018) Disease-modifying drugs in osteoarthritis: current understanding and future therapeutics. Expert Opin Emerg Drugs 23(4):331\u2013347. https:\/\/doi.org\/10.1080\/14728214.2018.1547706","journal-title":"Expert Opin Emerg Drugs"},{"issue":"14","key":"1902_CR57","doi-asserted-by":"publisher","first-page":"e33455","DOI":"10.1097\/md.0000000000033455","volume":"102","author":"JM Park","year":"2023","unstructured":"Park JM (2023) Association between obesity and osteoarthritis in the south korean older population: a nationwide population-based study. Medicine (Baltimore) 102(14):e33455. https:\/\/doi.org\/10.1097\/md.0000000000033455","journal-title":"Medicine (Baltimore)"},{"issue":"1","key":"1902_CR58","doi-asserted-by":"publisher","first-page":"127","DOI":"10.4049\/jimmunol.1800006","volume":"203","author":"MJ Park","year":"2019","unstructured":"Park MJ, Moon SJ, Baek JA, Lee EJ, Jung KA, Kim EK, Kim DS, Lee JH, Kwok SK, Min JK, Kim SJ, Park SH, Cho ML (2019) Metformin augments anti-inflammatory and chondroprotective properties of mesenchymal stem cells in experimental osteoarthritis. J Immunol 203(1):127\u2013136. https:\/\/doi.org\/10.4049\/jimmunol.1800006","journal-title":"J Immunol"},{"issue":"11 Suppl 3","key":"1902_CR59","doi-asserted-by":"publisher","first-page":"S108","DOI":"10.1097\/phm.0000000000000115","volume":"93","author":"AM Pourcho","year":"2014","unstructured":"Pourcho AM, Smith J, Wisniewski SJ, Sellon JL (2014) Intraarticular platelet-rich plasma injection in the treatment of knee osteoarthritis: review and recommendations. Am J Phys Med Rehabil 93(11 Suppl 3):S108\u2013S121. https:\/\/doi.org\/10.1097\/phm.0000000000000115","journal-title":"Am J Phys Med Rehabil"},{"key":"1902_CR60","doi-asserted-by":"publisher","DOI":"10.3390\/nu13072254","author":"M Rojas","year":"2021","unstructured":"Rojas M, Ch\u00e1vez-Castillo M, Pirela D, Parra H, Nava M, Chac\u00edn M, Angarita L, A\u00f1ez R, Salazar J, Ortiz R, Dur\u00e1n Ag\u00fcero S, Gravini-Donado M, Berm\u00fadez V, D\u00edaz-Camargo E (2021) Metabolic syndrome: is it time to add the central nervous system? Nutrients. https:\/\/doi.org\/10.3390\/nu13072254","journal-title":"Nutrients"},{"key":"1902_CR61","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-016-0254-3","volume":"23","author":"H Saeed","year":"2016","unstructured":"Saeed H, Ahsan M, Saleem Z, Iqtedar M, Islam M, Danish Z, Khan AM (2016) Mesenchymal stem cells (Mscs) as skeletal therapeutics - an update. J Biomed Sci 23:41. https:\/\/doi.org\/10.1186\/s12929-016-0254-3","journal-title":"J Biomed Sci"},{"issue":"1","key":"1902_CR62","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ecl.2013.09.009","volume":"43","author":"SL Samson","year":"2014","unstructured":"Samson SL, Garber AJ (2014) Metabolic syndrome. Endocrinol Metab Clin North Am 43(1):1\u201323. https:\/\/doi.org\/10.1016\/j.ecl.2013.09.009","journal-title":"Endocrinol Metab Clin North Am"},{"issue":"2","key":"1902_CR63","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1302\/0301-620x.104b2.Bjj-2022-0007","volume":"104-b","author":"CEH Scott","year":"2022","unstructured":"Scott CEH, Clement ND, Davis ET, Haddad FS (2022) Modern total hip arthroplasty: peak of perfection or room for improvement? Bone Joint J 104-b(2):189\u2013192. https:\/\/doi.org\/10.1302\/0301-620x.104b2.Bjj-2022-0007","journal-title":"Bone Joint J"},{"key":"1902_CR64","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241210166","author":"CH Tang","year":"2023","unstructured":"Tang CH (2023) Research of pathogenesis and novel therapeutics in arthritis 3.0. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms241210166","journal-title":"Int J Mol Sci"},{"issue":"2","key":"1902_CR65","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1038\/s41422-020-00441-1","volume":"31","author":"D Tang","year":"2021","unstructured":"Tang D, Chen X, Kang R, Kroemer G (2021) Ferroptosis: molecular mechanisms and health implications. Cell Res 31(2):107\u2013125. https:\/\/doi.org\/10.1038\/s41422-020-00441-1","journal-title":"Cell Res"},{"issue":"3","key":"1902_CR66","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/j.rdc.2018.03.009","volume":"44","author":"N Taylor","year":"2018","unstructured":"Taylor N (2018) Nonsurgical management of osteoarthritis knee pain in the older adult: an update. Rheum Dis Clin North Am 44(3):513\u2013524. https:\/\/doi.org\/10.1016\/j.rdc.2018.03.009","journal-title":"Rheum Dis Clin North Am"},{"issue":"7","key":"1902_CR67","doi-asserted-by":"publisher","first-page":"1928","DOI":"10.1002\/art.30333","volume":"63","author":"R Terkeltaub","year":"2011","unstructured":"Terkeltaub R, Yang B, Lotz M, Liu-Bryan R (2011) Chondrocyte amp-activated protein kinase activity suppresses matrix degradation responses to proinflammatory cytokines interleukin-1\u03b2 and tumor necrosis factor \u0391. Arthr Rheum 63(7):1928\u20131937. https:\/\/doi.org\/10.1002\/art.30333","journal-title":"Arthr Rheum"},{"issue":"1","key":"1902_CR68","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.joca.2019.06.015","volume":"28","author":"AM Valdes","year":"2020","unstructured":"Valdes AM (2020) Metabolic syndrome and osteoarthritis pain: common molecular mechanisms and potential therapeutic implications. Osteoarthr Cartil 28(1):7\u20139. https:\/\/doi.org\/10.1016\/j.joca.2019.06.015","journal-title":"Osteoarthr Cartil"},{"key":"1902_CR69","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.cytogfr.2018.10.002","volume":"44","author":"T Wang","year":"2018","unstructured":"Wang T, He C (2018) Pro-inflammatory cytokines: the link between obesity and osteoarthritis. Cytokine Growth Factor Rev 44:38\u201350. https:\/\/doi.org\/10.1016\/j.cytogfr.2018.10.002","journal-title":"Cytokine Growth Factor Rev"},{"issue":"1","key":"1902_CR70","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1186\/s13075-019-1915-x","volume":"21","author":"Y Wang","year":"2019","unstructured":"Wang Y, Hussain SM, Wluka AE, Lim YZ, Abram F, Pelletier JP, Martel-Pelletier J, Cicuttini FM (2019) Association between metformin use and disease progression in obese people with knee osteoarthritis: data from the osteoarthritis initiative-a prospective cohort study. Arthritis Res Ther 21(1):127. https:\/\/doi.org\/10.1186\/s13075-019-1915-x","journal-title":"Arthritis Res Ther"},{"issue":"6","key":"1902_CR71","doi-asserted-by":"publisher","first-page":"605","DOI":"10.5582\/bst.2018.01263","volume":"12","author":"C Wang","year":"2019","unstructured":"Wang C, Yang Y, Zhang Y, Liu J, Yao Z, Zhang C (2019) Protective effects of metformin against osteoarthritis through upregulation of sirt3-mediated pink1\/parkin-dependent mitophagy in primary chondrocytes. Biosci Trends 12(6):605\u2013612. https:\/\/doi.org\/10.5582\/bst.2018.01263","journal-title":"Biosci Trends"},{"key":"1902_CR72","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010059","author":"P Wei","year":"2022","unstructured":"Wei P, Bao R (2022) Intra-articular mesenchymal stem cell injection for knee osteoarthritis: mechanisms and clinical evidence. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms24010059","journal-title":"Int J Mol Sci"},{"issue":"12","key":"1902_CR73","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-019-0868-z","volume":"21","author":"C Xie","year":"2019","unstructured":"Xie C, Chen Q (2019) Adipokines: new therapeutic target for osteoarthritis? Curr Rheumatol Rep 21(12):71. https:\/\/doi.org\/10.1007\/s11926-019-0868-z","journal-title":"Curr Rheumatol Rep"},{"key":"1902_CR74","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19113534","author":"Y Yan","year":"2018","unstructured":"Yan Y, Zhou XE, Xu HE, Melcher K (2018) Structure and physiological regulation of Ampk. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms19113534","journal-title":"Int J Mol Sci"},{"issue":"1","key":"1902_CR75","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1186\/s13018-022-03225-y","volume":"17","author":"J Yan","year":"2022","unstructured":"Yan J, Feng G, Ma L, Chen Z, Jin Q (2022) Metformin alleviates osteoarthritis in mice by inhibiting chondrocyte ferroptosis and improving subchondral osteosclerosis and angiogenesis. J Orthop Surg Res 17(1):333. https:\/\/doi.org\/10.1186\/s13018-022-03225-y","journal-title":"J Orthop Surg Res"},{"issue":"1","key":"1902_CR76","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-023-03571-5","volume":"18","author":"S Yan","year":"2023","unstructured":"Yan S, Dong W, Li Z, Wei J, Han T, Wang J, Lin F (2023) Metformin regulates chondrocyte senescence and proliferation through Microrna-34a\/Sirt1 pathway in osteoarthritis. J Orthop Surg Res 18(1):198. https:\/\/doi.org\/10.1186\/s13018-023-03571-5","journal-title":"J Orthop Surg Res"},{"key":"1902_CR77","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-024-01496-x","author":"YZ Yang","year":"2024","unstructured":"Yang YZ, Cheng QH, Zhang AR, Qiu Y, Guo HZ (2024) Progress in the treatment of osteoarthritis with avocado-soybean unsaponifiable. Inflammopharmacology. https:\/\/doi.org\/10.1007\/s10787-024-01496-x","journal-title":"Inflammopharmacology"},{"issue":"1","key":"1902_CR78","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/s40519-023-01538-3","volume":"28","author":"J Yuan","year":"2023","unstructured":"Yuan J, Wang D, Zhang Y, Dou Q (2023) Genetically predicted obesity and risk of hip osteoarthritis. Eat Weight Disord 28(1):11. https:\/\/doi.org\/10.1007\/s40519-023-01538-3","journal-title":"Eat Weight Disord"},{"issue":"12","key":"1902_CR79","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1691\/ph.2020.0762","volume":"75","author":"M Zhang","year":"2020","unstructured":"Zhang M, Liu Y, Huan Z, Wang Y, Xu J (2020) Metformin protects chondrocytes against IL-1\u03b2 induced injury by regulation of the AMPK\/NF-\u03ba B signaling pathway. Pharmazie 75(12):632\u2013636. https:\/\/doi.org\/10.1691\/ph.2020.0762","journal-title":"Pharmazie"},{"issue":"11","key":"1902_CR80","doi-asserted-by":"publisher","first-page":"1506","DOI":"10.1016\/j.joca.2022.06.010","volume":"30","author":"Y Zhang","year":"2022","unstructured":"Zhang Y, Li D, Zhu Z, Chen S, Lu M, Cao P, Chen T, Li S, Xue S, Zhang Y, Zhu J, Ruan G, Ding C (2022) Evaluating the impact of metformin targets on the risk of osteoarthritis: a Mendelian randomization study. Osteoarthr Cartil 30(11):1506\u20131514. https:\/\/doi.org\/10.1016\/j.joca.2022.06.010","journal-title":"Osteoarthr Cartil"},{"key":"1902_CR81","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24065355","author":"M Zheng","year":"2023","unstructured":"Zheng M, Zhu Y, Wei K, Pu H, Peng R, Xiao J, Liu C, Sun X (2023) Metformin attenuates the inflammatory response via the regulation of synovial M1 macrophage in osteoarthritis. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms24065355","journal-title":"Int J Mol Sci"},{"key":"1902_CR82","doi-asserted-by":"publisher","DOI":"10.1038\/srep43245","volume":"7","author":"S Zhou","year":"2017","unstructured":"Zhou S, Lu W, Chen L, Ge Q, Chen D, Xu Z, Shi D, Dai J, Li J, Ju H, Cao Y, Qin J, Chen S, Teng H, Jiang Q (2017) Ampk deficiency in chondrocytes accelerated the progression of instability-induced and ageing-associated osteoarthritis in adult mice. Sci Rep 7:43245. https:\/\/doi.org\/10.1038\/srep43245","journal-title":"Sci Rep"},{"issue":"49","key":"1902_CR83","doi-asserted-by":"publisher","first-page":"E1672","DOI":"10.1503\/cmaj.220952","volume":"194","author":"Z Zhu","year":"2022","unstructured":"Zhu Z, Huang JY, Ruan G, Cao P, Chen S, Zhang Y, Han W, Chen T, Cai X, Liu J, Tang Y, Yu N, Wang Q, Hunter DJ, Wei JC, Ding C (2022) Metformin use and associated risk of total joint replacement in patients with type 2 diabetes: a population-based matched cohort study. CMAJ 194(49):E1672\u2013E1684. https:\/\/doi.org\/10.1503\/cmaj.220952","journal-title":"CMAJ"},{"issue":"3","key":"1902_CR84","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1021\/acscentsci.7b00028","volume":"3","author":"O Zilka","year":"2017","unstructured":"Zilka O, Shah R, Li B, Friedmann Angeli JP, Griesser M, Conrad M, Pratt DA (2017) On the mechanism of cytoprotection by Ferrostatin-1 and Liproxstatin-1 and the role of lipid peroxidation in ferroptotic cell death. ACS Cent Sci 3(3):232\u2013243. https:\/\/doi.org\/10.1021\/acscentsci.7b00028","journal-title":"ACS Cent Sci"}],"container-title":["Inflammopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10787-025-01902-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10787-025-01902-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10787-025-01902-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T19:04:51Z","timestamp":1761332691000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10787-025-01902-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,25]]},"references-count":84,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["1902"],"URL":"https:\/\/doi.org\/10.1007\/s10787-025-01902-y","relation":{},"ISSN":["0925-4692","1568-5608"],"issn-type":[{"value":"0925-4692","type":"print"},{"value":"1568-5608","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,25]]},"assertion":[{"value":"24 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 September 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 September 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not applicable to this article.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participation"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}