Abstract
The current study investigates if contrast-enhanced ultrasound (CEUS) or cytokine expression analysis (CEA) evaluating vascularization are capable of predicting the outcome of non-union therapy. Patients with tibial non-unions were surgically treated and participated in our follow-up program including perioperative collection of blood as well as CEUS analysis. Two groups were formed: Responders in group 1 (G1, N = 8) and Non-Responders in group 2 (G2, N = 5). Serum cytokine expression and local microperfusion were compared and correlated to the radiologic outcome. Evaluation of TNF-α expression revealed significantly lower values prior to first surgery in G1 (G1: 9.66 ± 0.96 pg/mL versus G2: 12.63 ± 1.2 pg/mL; p = 0.045); whereas after treatment both CEA and CEUS indicated a higher potential for angiogenesis in Responders. Logistic regression modelling revealed the highest predictive power regarding eventual osseous consolidation for the combination of both CEUS and serum CEA. The results provide first evidence regarding a link between changes in the serum expression of distinct pro-angiogenic cytokines and alterations in the local microperfusion assessed via both non-invasive and radiation-free diagnostic modalities. In addition, a combination of CEUS and CEA is a promising novel tool in early prediction of the outcome of non-union therapy.
Highlights
Fracture non-unions are common and occur in up to 30% [1]
This study aimed to investigate the diagnostic performance of contrast-enhanced ultrasound (CEUS) and peripheral cytokine expression analysis (CEA)
Initial studies investigating in the diagnostic performance of CEUS in context with tibial non-unions provided promising first results regarding the capabilities of CEUS
Summary
100,000 fractures develop a non-union each year in the United States alone [2]. The tibia is most susceptible to failed bone regeneration [3] and resulting non-unions have severe implications for Diagnostics 2018, 8, 55; doi:10.3390/diagnostics8030055 www.mdpi.com/journal/diagnostics. The “diamond concept” defines core factors that are mandatory for successful bone regeneration and non-union healing, emphasizing the importance of sufficient vascularity [4,5,6]. The Masquelet-therapy was developed to treat large-defect-sized non-unions by inducing angiogenesis and enhancing local bone biology resulting in osseous regeneration [7]. Earliest radiologic determination (X-ray and computed tomography) regarding the success of treatment is only possible after 6 months [1,2] and is limited due to radiation exposure [2]. Radiation-free diagnostic alternatives capable of an early determination of the outcome are warranted
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