{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T12:43:36Z","timestamp":1793105016189,"version":"4.5.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T00:00:00Z","timestamp":1753747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to determine if a higher proportion of Retrievers with cranial cruciate ligament disease (CCLD) had previous systemic exposure to fluoroquinolones or glucocorticoids compared to Retrievers without CCLD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Animals<\/jats:title><jats:p>Client-owned, Labrador and Golden Retrievers and Retriever crosses, aged 2\u201312\u202fyears old, were enrolled from Kansas State University and Washington State University with CCLD (cases) and without CCLD (nCCLD; healthy controls).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study was designed as a retrospective, multi-institutional case\u2013control study. Medical records (2019\u20132023) were reviewed for systemic and topical exposure to fluoroquinolones or glucocorticoids within 6\u202fmonths of CCLD exam or visit (nCCLD) or anytime throughout life prior to injury or visit. Data were analyzed using univariate and multivariate logistic regression analyses. The results were reported as coefficients, standard errors, <jats:italic>p<\/jats:italic>-values, and odds ratios with 95% confidence intervals. A <jats:italic>p<\/jats:italic>-value of &amp;lt;0.05 was considered significant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 419 dogs (216 cases and 203 controls) were enrolled in this study. The odds ratios of CCLD after systemic fluoroquinolone exposure were three times (CI: 1.01\u20138.90) higher than the odds ratios of CCLD without fluoroquinolone exposure. The odds ratios of CCLD after systemic glucocorticoid exposure were 3.51 times (CI: 1.94\u20136.37) higher than the odds ratios of CCLD without glucocorticoid exposure. Topical administration was not found to pose the same risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The findings of this study suggest that the administration of systemic fluoroquinolones or systemic glucocorticoids was identified as a risk factor for the development of CCLD in Retriever breeds. Prospective studies are needed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical relevance<\/jats:title><jats:p>Although not all risk factors for CCLD can be mitigated, systemic fluoroquinolones and\/or glucocorticoids should be used cautiously in Retriever breeds.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fvets.2025.1625530","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T04:10:47Z","timestamp":1753762247000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Fluoroquinolones and glucocorticoids as risk factors for cranial cruciate ligament disease in Retrievers"],"prefix":"10.3389","volume":"12","author":[{"given":"Jessica","family":"Bunch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"KuKanich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimena","family":"Kilian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexa","family":"Korsberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Butch","family":"KuKanich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Martinez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1818","DOI":"10.2460\/javma.232.12.1818","article-title":"Prevalence of and risk factors for hip dysplasia and cranial cruciate ligament deficiency in dogs","volume":"232","author":"Witsberger","year":"2008","journal-title":"J Am Vet Med Assoc"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1111\/j.1532-950X.2010.00654.x","article-title":"A review of the pathogenesis of canine cranial cruciate ligament disease as a basis for future preventive strategies","volume":"39","author":"Griffon","year":"2010","journal-title":"Vet Surg"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2460\/javma.23.01.0004","article-title":"Cranial cruciate ligament disease is perceived to be prevalent and is misunderstood in field trial sport","volume":"261","author":"Hynes","year":"2023","journal-title":"J Am Vet Med Assoc"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1335939","DOI":"10.3389\/fvets.2024.1335939","article-title":"Risk factors for the development of stifle injuries in canine agility athletes","volume":"11","author":"Kieves","year":"2024","journal-title":"Front Vet Sci"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1111\/j.1532-950X.2009.00532.x","article-title":"Age, Tibial plateau angle, sex, and weight as risk factors for contralateral rupture of the cranial cruciate ligament in Labradors","volume":"38","author":"Buote","year":"2009","journal-title":"Vet Surg"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s12917-022-03146-2","article-title":"Risk factors for cranial cruciate ligament rupture in dogs participating in canine agility","volume":"18","author":"Sellon","year":"2022","journal-title":"BMC Vet Res"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"318","DOI":"10.2460\/javma.24.06.0406","article-title":"Age of neutering contributes to risk of cruciate ligament rupture in Labrador retrievers","volume":"263","author":"DeForge","year":"2025","journal-title":"J Am Vet Med Assoc"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1007\/s40264-013-0089-8","article-title":"Tendon injury and fluoroquinolone use: a systematic review","volume":"36","author":"Stephenson","year":"2013","journal-title":"Drug Saf"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"633","DOI":"10.2165\/00002018-200528070-00005","article-title":"Corticosteroid-associated tendinopathies: an analysis of the published literature and spontaneous pharmacovigilance data","volume":"28","author":"Blanco","year":"2005","journal-title":"Drug Saf"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e33","DOI":"10.1097\/PHM.0000000000000816","article-title":"Two unique cases of ciprofloxacin-associated avulsion of ligament and tendon","volume":"97","author":"Smith","year":"2018","journal-title":"Am J Phys Med Rehabil"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"e20331","DOI":"10.1016\/j.heliyon.2023.e20331","article-title":"Prevalence, risk factors and treatment outcomes of fluoroquinolones-associated tendinopathy in tuberculosis patients at university hospital, Thailand","volume":"9","author":"Chongboonwatana","year":"2023","journal-title":"Heliyon"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1177\/03635465000280031401","article-title":"The effect of ciprofloxacin on tendon, paratenon, and capsular fibroblast metabolism","volume":"28","author":"Williams","year":"2000","journal-title":"Am J Sports Med"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.taap.2011.08.019","article-title":"The effects of levofloxacin on rabbit anterior cruciate ligament cells in vitro","volume":"257","author":"Deng","year":"2011","journal-title":"Toxicol Appl Pharmacol"},{"key":"ref14","first-page":"93","article-title":"The metabolic effects of quinolones and steroids on human ligament cells: an in vitro study","volume":"34","author":"Luciani","year":"2020","journal-title":"J Biol Regul Homeost Agents"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1682","DOI":"10.2106\/00004623-199511000-00006","article-title":"Effects of local injection of corticosteroids on the healing of ligaments. A follow-up report","volume":"77","author":"Wiggins","year":"1995","journal-title":"J Bone Joint Surg Am"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"e0262206","DOI":"10.1371\/journal.pone.0262206","article-title":"Effects of long-term and high-dose administration of glucocorticoids on the cranial cruciate ligament in healthy beagle dogs","volume":"17","author":"Shimada","year":"2022","journal-title":"PLoS One"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.pmrj.2010.10.003","article-title":"Musculoskeletal complications of fluoroquinolones: guidelines and precautions for usage in the athletic population","volume":"3","author":"Hall","year":"2011","journal-title":"PM&R"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"422","DOI":"10.4085\/1062-6050-49.2.09","article-title":"Fluoroquinolones and tendinopathy: a guide for athletes and sports clinicians and a systematic review of the literature","volume":"49","author":"Lewis","year":"2014","journal-title":"J Athl Train"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1404","DOI":"10.1086\/375078","article-title":"Fluoroquinolone-associated tendinopathy: a critical review of the literature","volume":"36","author":"Khaliq","year":"2003","journal-title":"Clin Infect Dis"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1002\/phar.1761","article-title":"Fluoroquinolone-associated tendinopathy: does levofloxacin pose the greatest risk?","volume":"36","author":"Bidell","year":"2016","journal-title":"Pharmacother J Hum Pharmacol Drug Ther"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1093\/bmb\/ldz006","article-title":"Biological and chemical changes in fluoroquinolone-associated tendinopathies: a systematic review","volume":"130","author":"Bisaccia","year":"2019","journal-title":"Br Med Bull"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1002\/jor.24475","article-title":"Tendon and ligament healing and current approaches to tendon and ligament regeneration","volume":"38","author":"Leong","year":"2020","journal-title":"J Orthop Res"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.1002\/jbmr.3199","article-title":"Tendons and ligaments: connecting developmental biology to musculoskeletal disease pathogenesis","volume":"32","author":"Asahara","year":"2017","journal-title":"J Bone Miner Res"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"91","DOI":"10.3415\/VCOT-10-04-0055","article-title":"Update on the aetiopathogenesis of canine cranial cruciate ligament disease","volume":"24","author":"Comerford","year":"2011","journal-title":"Vet Comp Orthop Traumatol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"811","DOI":"10.2460\/javma.1999.215.06.811","article-title":"Breed, sex, and body weight as risk factors for rupture of the cranial cruciate ligament in young dogs","volume":"215","author":"Duval","year":"1999","journal-title":"J Am Vet Med Assoc"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"305","DOI":"10.2754\/avb200069040305","article-title":"Predisposition of dog breeds to rupture of the cranial cruciate ligament","volume":"69","author":"Ne\u010das","year":"2000","journal-title":"Acta Vet Brno"}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2025.1625530\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T04:10:47Z","timestamp":1753762247000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2025.1625530\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,29]]},"references-count":26,"alternative-id":["10.3389\/fvets.2025.1625530"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2025.1625530","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,29]]},"article-number":"1625530"}}