title: Fluoroquinolones impair tendon healing in a rat rotator cuff repair model: a preliminary study.
abstract: BACKGROUND
  Recent studies suggest that fluoroquinolone antibiotics predispose tendons to tendinopathy and/or rupture. However, no investigations on the reparative capacity of tendons exposed to fluoroquinolones have been conducted.
  
  
  OBJECTIVE
  Fluoroquinolone-treated animals will have inferior biochemical, histological, and biomechanical properties at the healing tendon-bone enthesis compared with controls.
  
  
  METHODS
  Controlled laboratory study.
  
  
  METHODS
  Ninety-two rats underwent rotator cuff repair and were randomly assigned to 1 of 4 groups: (1) preoperative (Preop), whereby animals received fleroxacin for 1 week preoperatively; (2) pre- and postoperative (Pre/Postop), whereby animals received fleroxacin for 1 week preoperatively and for 2 weeks postoperatively; (3) postoperative (Postop), whereby animals received fleroxacin for 2 weeks postoperatively; and (4) control, whereby animals received vehicle for 1 week preoperatively and for 2 weeks postoperatively. Rats were euthanized at 2 weeks postoperatively for biochemical, histological, and biomechanical analysis. All data were expressed as mean ± standard error of the mean (SEM). Statistical comparisons were performed using either 1-way or 2-way ANOVA, with P < .05 considered significant.
  
  
  RESULTS
  Reverse transcriptase quantitative polymerase chain reaction (RTqPCR) analysis revealed a 30-fold increase in expression of matrix metalloproteinase (MMP)-3, a 7-fold increase in MMP-13, and a 4-fold increase in tissue inhibitor of metalloproteinases (TIMP)-1 in the Pre/Postop group compared with the other groups. The appearance of the healing enthesis in all treated animals was qualitatively different than that in controls. The tendons were friable and atrophic. All 3 treated groups showed significantly less fibrocartilage and poorly organized collagen at the healing enthesis compared with control animals. There was a significant difference in the mode of failure, with treated animals demonstrating an intrasubstance failure of the supraspinatus tendon during testing. In contrast, only 1 of 10 control samples failed within the tendon substance. The healing enthesis of the Pre/Postop group displayed significantly reduced ultimate load to failure compared with the Preop, Postop, and control groups. There was no significant difference in load to failure in the Preop group compared with the Postop group. Pre/Postop animals demonstrated significantly reduced cross-sectional area compared with the Postop and control groups. There was also a significant reduction in area between the Preop and control groups.
  
  
  CONCLUSIONS
  In this preliminary study, fluoroquinolone treatment negatively influenced tendon healing.
  
  
  CONCLUSIONS
  These findings indicate that there was an active but inadequate repair response that has potential clinical implications for patients who are exposed to fluoroquinolones before tendon repair surgery.
authors.affiliation: Laboratory for Soft Tissue Research, Hospital for Special Surgery, New York, New York, USA foxa@hss.edu ajsfox27@hotmail.com.
authors.forename: Alice J S
authors.initials: AJ
authors.lastname: Fox
authors.affiliation: Laboratory for Soft Tissue Research, Hospital for Special Surgery, New York, New York, USA.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Schär
authors.affiliation: Laboratory for Soft Tissue Research, Hospital for Special Surgery, New York, New York, USA.
authors.forename: Florian
authors.initials: F
authors.lastname: Wanivenhaus
authors.affiliation: Laboratory for Soft Tissue Research, Department of Biomechanics, Hospital for Special Surgery, New York, New York, USA.
authors.forename: Tony
authors.initials: T
authors.lastname: Chen
authors.affiliation: Laboratory for Soft Tissue Research, Hospital for Special Surgery, New York, New York, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Attia
authors.affiliation: Laboratory for Soft Tissue Research, Hospital for Special Surgery, New York, New York, USA.
authors.forename: Nikolaus B
authors.initials: NB
authors.lastname: Binder
authors.affiliation: Laboratory for Soft Tissue Research, Hospital for Special Surgery, New York, New York, USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Otero
authors.affiliation: Department of Biomechanics, Hospital for Special Surgery, New York, New York, USA.
authors.forename: Susannah L
authors.initials: SL
authors.lastname: Gilbert
authors.affiliation: Healthcare Research Institute, Hospital for Special Surgery, New York, New York, USA.
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Nguyen
authors.affiliation: Laboratory for Soft Tissue Research, Hospital for Special Surgery, New York, New York, USA.
authors.forename: Salma
authors.initials: S
authors.lastname: Chaudhury
authors.affiliation: Laboratory for Soft Tissue Research, Hospital for Special Surgery, New York, New York, USA.
authors.forename: Russell F
authors.initials: RF
authors.lastname: Warren
authors.affiliation: Laboratory for Soft Tissue Research, Hospital for Special Surgery, New York, New York, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rodeo
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects*; D051445:Fibrocartilage / Q000473:pathology; D016576:Fleroxacin / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D008853:Microscopy; D023421:Models, Animal; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017006:Rotator Cuff / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D013314:Stress, Mechanical; D013710:Tendons / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000890:Anti-Infective Agents; D012333:RNA, Messenger; C576839:TIMP1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat; D019278:Matrix Metalloproteinase 3; D016576:Fleroxacin
keywords: fleroxacin; fluoroquinolone; rotator cuff repair; tendinopathy; tendon healing