Evaluation of matrix metalloproteases as early biomarkers for bone regeneration during the applied Masquelet therapy for non-unions.

INTRODUCTION: In the current study, we sought to determine if serum concentrations of MMPs correlate with bone regeneration occurring during the course of the Masquelet-therapy and to identify if MMPs may serve as early biomarkers reflecting successful bone regeneration and tissue remodeling. MATERIAL AND METHODS: This study was designed as a prospective clinical observer study. We compared serum samples over the time of treatment, as a matched-pair analysis, from 10 patients who were treated successfully with the Masquelet-therapy (Responder) with 10 patients who did not respond to the Masquelet-therapy (Non-Responder). The quantitative measurement was performed with Luminex Performance Human High Sensitivity Assays according to manufacturer's instructions. The lab technician performing the Luminex assays was blinded to both patient data and clinical outcome. RESULTS: Analysis of the expression pattern of MMP-2, -8 and -9 showed significant differences between groups. Two days after the first step of the Masquelet therapy Responder showed peak values of MMP-8 and MMP-9 that where significantly higher (p = 0.003 and p = 0.042, respectively) than in Non-Responder. In contrast serum levels of MMP-2 were lower after the first step of the Masquelet therapy in the Non-Responder group. The ratio of MMP-9 and MMP-2 was significantly higher in the Responder group two days after step I (p = 0.031) as well as 4 weeks after step II (p = 0.030). CONCLUSION: The findings of the current study emphasize the potential role of MMPs as biomarkers in bone remodeling. In particular, a distinct expression of MMP-2 correlates with successful bone regeneration, whereas initial overexpression of MMP-2 serum levels might identify patients that have a higher risk for a poor outcome of the Masquelet-therapy. Furthermore, we were able to introduce the serum analysis of the ratio of MMP-9 and MMP-2 as promising novel modality for early prediction of the outcome of the Masquelet therapy. Further analysis of this ratio over time subsequent to the second step might serve as an early indicator of a favorable response to the induced membrane technique.

CCL-2 as a possible early marker for remission after traumatic spinal cord injury.

STUDY DESIGN: Prospective observational study. OBJECTIVES: To describe the correlation between CCL-2, CCL-3, CCL-4 and CXCL-5 serum levels and remission after traumatic spinal cord injury (SCI) in a human protocol compared with animal studies. SETTING: Germany, Rhineland-Palatinate (Rheinland-Pfalz). METHODS: We examined the serum levels of CCL-2, CCL-3, CCL-4 and CXCL-5 over a 12-week period; in particular, at admission and 4, 9 and 12 h, 1 and 3 days and 1, 2, 4, 8 and 12 weeks after trauma. According to our study design, we matched 10 patients with TSCI and neurological remission with 10 patients with an initial ASIA A grade and no neurological remission. In all, 10 patients with vertebral fracture without neurological deficits served as control. Our analysis was performed using a Luminex Cytokine Panel. Multivariate logistic regression models were used to examine the predictive value with respect to neurological remission vs no neurological remission. RESULTS: The results of our study showed differences in the serum expression patterns of CCL-2 in association with the neurological remission (CCL-2 at admission P=0.013). Serum levels of CCL-2 and CCL-4 were significantly different in patients with and without neurological remission. The favored predictive model resulted in an area under the curve (AUC) of 93.1% in the receiver operating characteristic (ROC) analysis. CONCLUSIONS: Our results indicate that peripheral serum analysis is a suitable concept for predicting the patient's potential for neurological remission after TSCI. Furthermore, the initial CCL-2 concentration provides an additional predictive value compared with the NLI (neurological level of injury). Therefore, the present study introduces a promising approach for future monitoring concepts and tracking techniques for current therapies. The results indicate that future investigations with an enlarged sample size are needed in order to develop monitoring, prognostic and scoring systems.