Impact of Fluoroquinolones on Tendon Health: A Comprehensive Overview for the General Population and Athletes
DOI:
https://doi.org/10.12775/QS.2024.31.55763Keywords
fluoroquinolones, adverse effects, tendinitis, tendon rupture, tendinopathyAbstract
Introduction: Fluoroquinolones are a class of broad-spectrum antibiotics widely used to treat various bacterial infections. Despite their effectiveness, increasing evidence links fluoroquinolones to tendinopathy and tendon rupture, with cases occurring shortly after initiation or even months post-therapy. This review provides a comprehensive overview of the impact of fluoroquinolones on tendon health - highlighting the underlying pathomechanisms, clinical manifestations, and epidemiology of fluoroquinolone-associated tendinopathy.
Purpose of the work: The purpose of this study is to review the effects of fluoroquinolones on tendon health in the general population. Special attention is given to the athletes, who are particularly vulnerable to tendon injuries.
Materials and methods: A comprehensive analysis of research articles available on PubMed, Google Scholar, Web of Science, Embase, and Scopus was conducted using search terms related to: "fluoroquinolones," "tendinopathy," "tendon rupture," "athletes" and "connective tissue damage."
Results: Fluoroquinolones are linked to an increased risk of tendinopathy and tendon rupture, particularly among those with certain risk factors, including athletes. Understanding the mechanisms by which fluoroquinolones affect tendon tissue and recognizing early signs of tendon damage can help mitigate these risks. Prevention strategies, including cautious prescribing fluoroquinolones and targeted rehabilitation programmes, may reduce the adverse effects of fluoroquinolone usage, particularly in high-risk groups like athletes.
References
Barberán J, de la Cuerda A, Tejeda González MI, López Aparicio A, Monfort Vinuesa C, Ramos Sánchez A, Barberán LC. Safety of fluoroquinolones. Rev Esp Quimioter. 2024 Apr;37(2):127-133. doi: 10.37201/req/143.2023. Epub 2023 Dec 22. PMID: 38140798; PMCID: PMC10945095.
Pham TDM, Ziora ZM, Blaskovich MAT. Quinolone antibiotics. Medchemcomm. 2019 Jun 28;10(10):1719-1739. doi: 10.1039/c9md00120d. PMID: 31803393; PMCID: PMC6836748.
LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Fluoroquinolones. 2020 Mar 10. PMID: 31643179.
Farmakologia: podstawy farmakoterapii: podręcznik dla studentów medycyny i lekarz. Warszawa: Wydawnictwo Lekarskie PZWL, 2003. ISBN 83-200-3350-0
Lewis T, Cook J. Fluoroquinolones and tendinopathy: a guide for athletes and sports clinicians and a systematic review of the literature. J Athl Train. 2014 May-Jun;49(3):422-7. doi: 10.4085/1062-6050-49.2.09. Epub 2014 Apr 24. PMID: 24762232; PMCID: PMC4080593.
Tillett E, Loosemore M. Setting standards for the prevention and management of travellers' diarrhoea in elite athletes: an audit of one team during the Youth Commonwealth Games in India. Br J Sports Med. 2009 Dec;43(13):1045-8. doi: 10.1136/bjsm.2009.063396. Epub 2009 Oct 25. PMID: 19858110.
Baggio D, Ananda-Rajah MR. Fluoroquinolone antibiotics and adverse events. Aust Prescr. 2021 Oct;44(5):161-164. doi: 10.18773/austprescr.2021.035. Epub 2021 Oct 1. PMID: 34728881; PMCID: PMC8542490.
Alves C, Mendes D, Marques FB. Fluoroquinolones and the risk of tendon injury: a systematic review and meta-analysis. Eur J Clin Pharmacol. 2019 Oct;75(10):1431-1443. doi: 10.1007/s00228-019-02713-1. Epub 2019 Jul 4. PMID: 31270563.
Khaliq Y, Zhanel GG. Fluoroquinolone-associated tendinopathy: a critical review of the literature. Clin Infect Dis. 2003 Jun 1;36(11):1404-10. doi: 10.1086/375078. Epub 2003 May 20. PMID: 12766835.
Hall MM, Finnoff JT, Smith J. Musculoskeletal complications of fluoroquinolones: guidelines and precautions for usage in the athletic population. PM R. 2011 Feb;3(2):132-42. doi: 10.1016/j.pmrj.2010.10.003. PMID: 21333952.
Lang TR, Cook J, Rio E, Gaida JE. What tendon pathology is seen on imaging in people who have taken fluoroquinolones? A systematic review. Fundam Clin Pharmacol. 2017 Feb;31(1):4-16. doi: 10.1111/fcp.12228. Epub 2016 Oct 5. PMID: 27477928.
Bolon B. Mini-Review: Toxic Tendinopathy. Toxicol Pathol. 2017 Oct;45(7):834-837. doi: 10.1177/0192623317711614. Epub 2017 May 28. PMID: 28553748.
Bidell MR, Lodise TP. Fluoroquinolone-Associated Tendinopathy: Does Levofloxacin Pose the Greatest Risk? Pharmacotherapy. 2016 Jun;36(6):679-93. doi: 10.1002/phar.1761. Epub 2016 Jun 11. PMID: 27138564.
Benjamin M, Kaiser E, Milz S. Structure-function relationships in tendons: a review. J Anat. 2008 Mar;212(3):211-28. doi: 10.1111/j.1469-7580.2008.00864.x. PMID: 18304204; PMCID: PMC2408985.
Kjaer M. Role of extracellular matrix in adaptation of tendon and skeletal muscle to mechanical loading. Physiol Rev. 2004 Apr;84(2):649-98. doi: 10.1152/physrev.00031.2003. PMID: 15044685.
Longo UG, Ronga M, Maffulli N. Achilles tendinopathy. Sports Med Arthrosc Rev. 2009 Jun;17(2):112-26. doi: 10.1097/JSA.0b013e3181a3d625. PMID: 19440139.
Sharma P, Maffulli N. Biology of tendon injury: healing, modeling and remodeling. J Musculoskelet Neuronal Interact. 2006 Apr-Jun;6(2):181-90. PMID: 16849830.
Kannus P. Structure of the tendon connective tissue. Scand J Med Sci Sports. 2000 Dec;10(6):312-20. doi: 10.1034/j.1600-0838.2000.010006312.x. PMID: 11085557.
Juras V, Winhofer Y, Szomolanyi P, Vosshenrich J, Hager B, Wolf P, Weber M, Luger A, Trattnig S. Multiparametric MR Imaging Depicts Glycosaminoglycan Change in the Achilles Tendon during Ciprofloxacin Administration in Healthy Men: Initial Observation. Radiology. 2015 Jun;275(3):763-71. doi: 10.1148/radiol.15140484. Epub 2015 Feb 4. PMID: 25654669; PMCID: PMC4441530.
Gough AW, Kasali OB, Sigler RE, Baragi V. Quinolone arthropathy--acute toxicity to immature articular cartilage. Toxicol Pathol. 1992;20(3 Pt 1):436-49; discussion 449-50. doi: 10.1177/019262339202000313. PMID: 1295072.
Sendzik J, Lode H, Stahlmann R. Quinolone-induced arthropathy: an update focusing on new mechanistic and clinical data. Int J Antimicrob Agents. 2009 Mar;33(3):194-200. doi: 10.1016/j.ijantimicag.2008.08.004. Epub 2008 Oct 2. PMID: 18835137.
Sheng ZG, Peng S, Wang CY, Li HB, Hajela RK, Wang YE, Li QQ, Liu MF, Dong YS, Han G. Apoptosis in microencapsulated juvenile rabbit chondrocytes induced by ofloxacin: role played by beta(1)-integrin receptor. J Pharmacol Exp Ther. 2007 Jul;322(1):155-65. doi: 10.1124/jpet.106.118224. Epub 2007 Mar 30. PMID: 17400890.
Badal S, Her YF, Maher LJ 3rd. Nonantibiotic Effects of Fluoroquinolones in Mammalian Cells. J Biol Chem. 2015 Sep 4;290(36):22287-97. doi: 10.1074/jbc.M115.671222. Epub 2015 Jul 23. PMID: 26205818; PMCID: PMC4571980.
Van der Linden PD, Sturkenboom MC, Herings RM, Leufkens HG, Stricker BH. Fluoroquinolones and risk of Achilles tendon disorders: case-control study. BMJ. 2002 Jun 1;324(7349):1306-7. doi: 10.1136/bmj.324.7349.1306. PMID: 12039823; PMCID: PMC113766.
Ștefan CS, Nechita A, Dragostin OM, Fulga A, Lisă EL, Vatcu R, Dragostin I, Velicescu C, Fulga I. Drugs Associated with Adverse Effects in Vulnerable Groups of Patients. Clin Pract. 2024 May 31;14(3):1010-1020. doi: 10.3390/clinpract14030080. PMID: 38921258; PMCID: PMC11203099.
Akali AU, Niranjan NS. Management of bilateral Achilles tendon rupture associated with ciprofloxacin: a review and case presentation. J Plast Reconstr Aesthet Surg. 2008 Jul;61(7):830-4. doi: 10.1016/j.bjps.2006.08.005. Epub 2007 Apr 3. PMID: 17409040.
Kirchgesner T, Larbi A, Omoumi P, Malghem J, Zamali N, Manelfe J, Lecouvet F, Vande Berg B, Djebbar S, Dallaudière B. Drug-induced tendinopathy: from physiology to clinical applications. Joint Bone Spine. 2014 Dec;81(6):485-92. doi: 10.1016/j.jbspin.2014.03.022. Epub 2014 Jun 21. PMID: 24962977.
De Jesus JO, Parker L, Frangos AJ, Nazarian LN. Accuracy of MRI, MR arthrography, and ultrasound in the diagnosis of rotator cuff tears: a meta-analysis. AJR Am J Roentgenol. 2009 Jun;192(6):1701-7. doi: 10.2214/AJR.08.1241. PMID: 19457838.
Maffulli N, Sharma P, Luscombe KL. Achilles tendinopathy: aetiology and management. J R Soc Med. 2004 Oct;97(10):472-6. doi: 10.1177/0141076809701004. PMID: 15459257; PMCID: PMC1079614.
Magra M, Maffulli N. Matrix metalloproteases: a role in overuse tendinopathies. Br J Sports Med. 2005 Nov;39(11):789-91. doi: 10.1136/bjsm.2005.017855. PMID: 16244185; PMCID: PMC1725078.
Gaida JE, Cook JL, Bass SL. Adiposity and tendinopathy. Disabil Rehabil. 2008;30(20-22):1555-62. doi: 10.1080/09638280701786864. PMID: 18608380.
Godoy-Santos AL, Bruschini H, Cury J, Srougi M, de Cesar-Netto C, Fonseca LF, Maffulli N. Fluoroquinolones and the Risk of Achilles Tendon Disorders: Update on a Neglected Complication. Urology. 2018 Mar;113:20-25. doi: 10.1016/j.urology.2017.10.017. Epub 2017 Oct 23. PMID: 29074337.
Van der Linden PD, van de Lei J, Nab HW, Knol A, Stricker BH. Achilles tendinitis associated with fluoroquinolones. Br J Clin Pharmacol. 1999 Sep;48(3):433-7. doi: 10.1046/j.1365-2125.1999.00016.x. PMID: 10510157; PMCID: PMC2014320.
Wilton LV, Pearce GL, Mann RD. A comparison of ciprofloxacin, norfloxacin, ofloxacin, azithromycin and cefixime examined by observational cohort studies. Br J Clin Pharmacol. 1996 Apr;41(4):277-84. doi: 10.1046/j.1365-2125.1996.03013.x. PMID: 8730972; PMCID: PMC2042595.
Pantalone A, Abate M, D'Ovidio C, Carnevale A, Salini V. Diagnostic failure of ciprofloxacin-induced spontaneous bilateral Achilles tendon rupture: case-report and medical-legal considerations. Int J Immunopathol Pharmacol. 2011 Apr-Jun;24(2):519-22. doi: 10.1177/039463201102400227. PMID: 21658328.
Tsai WC, Hsu CC, Chen HC, Hsu YH, Lin MS, Wu CW, Pang JH. Ciprofloxacin-mediated inhibition of tenocyte migration and down-regulation of focal adhesion kinase phosphorylation. Eur J Pharmacol. 2009 Apr 1;607(1-3):23-6. doi: 10.1016/j.ejphar.2009.02.006. Epub 2009 Feb 14. PMID: 19232343.
Corrao G, Zambon A, Bertù L, Mauri A, Paleari V, Rossi C, Venegoni M. Evidence of tendinitis provoked by fluoroquinolone treatment: a case-control study. Drug Saf. 2006;29(10):889-96. doi: 10.2165/00002018-200629100-00006. PMID: 16970512.
Williams RJ 3rd, Attia E, Wickiewicz TL, Hannafin JA. The effect of ciprofloxacin on tendon, paratenon, and capsular fibroblast metabolism. Am J Sports Med. 2000 May-Jun;28(3):364-9. doi: 10.1177/03635465000280031401. PMID: 10843129.
Greene BL. Physical therapist management of fluoroquinolone-induced Achilles tendinopathy. Phys Ther. 2002 Dec;82(12):1224-31. PMID: 12444881.
Fahlström M, Jonsson P, Lorentzon R, Alfredson H. Chronic Achilles tendon pain treated with eccentric calf-muscle training. Knee Surg Sports Traumatol Arthrosc. 2003 Sep;11(5):327-33. doi: 10.1007/s00167-003-0418-z. Epub 2003 Aug 26. PMID: 12942235.
Sayana MK, Maffulli N. Eccentric calf muscle training in non-athletic patients with Achilles tendinopathy. J Sci Med Sport. 2007 Feb;10(1):52-8. doi: 10.1016/j.jsams.2006.05.008. Epub 2006 Jul 7. PMID: 16828343.
Gürbay A, Garrel C, Osman M, Richard MJ, Favier A, Hincal F. Cytotoxicity in ciprofloxacin-treated human fibroblast cells and protection by vitamin E. Hum Exp Toxicol. 2002 Dec;21(12):635-41. doi: 10.1191/0960327102ht305oa. PMID: 12540033.
Tsai WC, Yang YM. Fluoroquinolone-associated tendinopathy. Chang Gung Med J. 2011 Sep-Oct;34(5):461-7. PMID: 22035890.
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