Low intensity pulsed ultrasound in the treatment of long bone nonunions: Evaluation of cytokine expression as a tool for objectifying nonunion therapy.

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. CONCLUSION: 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.