title: Low intensity pulsed ultrasound in the treatment of long bone nonunions: Evaluation of cytokine expression as a tool for objectifying nonunion therapy.
abstract: BACKGROUND
  Nonunion is one of the most common complications in bone healing. After several clinical studies, the effect of low intensity pulsed ultrasound (LIPUS) in the treatment of nonunions remains unclear because of the difficulty in evaluating its effect on bone healing. In former studies, the analysis of serum cytokine expression patterns over time has proven to be an objective method for showing the bone healing process and evaluating nonunion therapies. This study evaluates LIPUS as a treatment option for patients with nonunions based on the analysis of serum cytokine expression.
  
  
  METHODS
  In this prospective, single institution study, venous blood samples from 23 patients were taken from October 2012 to October 2013 before starting LIPUS therapy and at the end of week 1 and 2 and after 1, 2, and 3 months. Patients attended clinical and radiological follow-up examinations at the same intervals. After treating all patients according to the LIPUS therapy protocol, we divided them into two groups: Group 1 consisted of patients with healing at the nonunion site, and Group 2 consisted of patients with failed nonunion therapy. We measured transforming growth factor-β1 (TGF-β1), platelet-derived growth factor (PDGF), and basic fibroblastic growth factor (bFGF) at all time-points.
  
  
  RESULTS
  The TGF-β1 serum concentration increased from the pre-treatment value to 1 week within the unsuccessful group. Otherwise, no significant differences between groups in measured cytokines during LIPUS therapy could be detected.
  
  
  CONCLUSIONS
  Our findings suggest that LIPUS does not lead to a significant increase in cytokine levels in patients with nonunions. It is likely that "successful" treatment can be attributed to spontaneous healing. Our results suggest that LIPUS is not a proper treatment for long bone nonunions.
authors.affiliation: HTRG - Heidelberg Trauma Research Group, Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital, Schlierbacher Landstraße 200a, 69118 Heidelberg, Baden-Württemberg, Germany.
authors.forename: Arash
authors.initials: A
authors.lastname: Moghaddam
authors.affiliation: HTRG - Heidelberg Trauma Research Group, Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital, Schlierbacher Landstraße 200a, 69118 Heidelberg, Baden-Württemberg, Germany.
authors.forename: Timur Mert
authors.initials: TM
authors.lastname: Yildirim
authors.affiliation: HTRG - Heidelberg Trauma Research Group, Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital, Schlierbacher Landstraße 200a, 69118 Heidelberg, Baden-Württemberg, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Westhauser
authors.affiliation: BG Trauma Centre Ludwigshafen, Ludwig-Guttmann-Str. 13, 67071 Ludwigshafen, Rheinland-Pfalz, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Danner
authors.affiliation: HTRG - Heidelberg Trauma Research Group, Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital, Schlierbacher Landstraße 200a, 69118 Heidelberg, Baden-Württemberg, Germany.
authors.forename: Tyler
authors.initials: T
authors.lastname: Swing
authors.affiliation: Institute of Medical Biometry and Informatics, University of Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Baden-Württemberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bruckner
authors.affiliation: BG Trauma Centre Ludwigshafen, Ludwig-Guttmann-Str. 13, 67071 Ludwigshafen, Rheinland-Pfalz, Germany.
authors.forename: Bahram
authors.initials: B
authors.lastname: Biglari
keywords: Cytokines; Low intensity pulsed ultrasound; Nonunion; PDGF; TGF-β1; bFGF