Haubruck P, Heller R, Apitz P, Kammerer A, Alamouti A, Daniel V, Schmidmaier G, Moghaddam A
Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Trauma and Reconstructive Surgery, Heidelberg University Hospital, Schlierbacher Landstrasse 200a, D-69118 Heidelberg, Germany.
Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Trauma and Reconstructive Surgery, Heidelberg University Hospital, Schlierbacher Landstrasse 200a, D-69118 Heidelberg, Germany.
Injury. 2018 Oct;49(10):1732-1738. doi: 10.1016/j.injury.2018.07.015. Epub 2018 Jul 24.
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.
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.
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).
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.
在本研究中，我们试图确定血清基质金属蛋白酶（MMPs）浓度是否与Masquelet技术治疗过程中发生的骨再生相关，并确定MMPs是否可作为反映成功骨再生和组织重塑的早期生物标志物。
本研究设计为一项前瞻性临床观察研究。我们采用配对分析方法，比较了10例接受Masquelet技术成功治疗的患者（反应者）和10例对Masquelet技术无反应的患者（无反应者）在治疗期间的血清样本。根据制造商的说明，使用Luminex性能人类高灵敏度检测方法进行定量测量。进行Luminex检测的实验室技术人员对患者数据和临床结果均不知情。
MMP-2、-8和-9表达模式的分析显示两组之间存在显著差异。在Masquelet治疗第一步后的两天，反应者的MMP-8和MMP-9峰值显著高于无反应者（分别为p = 0.003和p = 0.042）。相比之下，无反应者组在Masquelet治疗第一步后MMP-2的血清水平较低。在第一步后两天（p = 0.031）以及第二步后4周（p = 0.030），反应者组中MMP-9与MMP-2的比值显著更高。
本研究结果强调了MMPs作为骨重塑生物标志物的潜在作用。特别是，MMP-2的独特表达与成功的骨再生相关，而MMP-2血清水平的初始过度表达可能识别出Masquelet治疗效果不佳风险较高的患者。此外，我们能够引入MMP-9与MMP-2比值的血清分析作为早期预测Masquelet治疗结果的有前景的新方法。在第二步之后对该比值随时间的进一步分析可能作为对诱导膜技术良好反应的早期指标。
