Fischer Christian, Doll Julian, Tanner Michael, Bruckner Thomas, Zimmermann Gerald, Helbig Lars, Biglari Bahram, Schmidmaier Gerhard, Moghaddam Arash
Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Trauma and Reconstructive Surgery, Heidelberg University Hospital. HTRG - Heidelberg Trauma Research Group, Heidelberg, D-69118 Germany.
Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Trauma and Reconstructive Surgery, Heidelberg University Hospital. HTRG - Heidelberg Trauma Research Group, Heidelberg, D-69118 Germany.
Injury. 2016 Feb;47(2):342-9. doi: 10.1016/j.injury.2015.11.007. Epub 2015 Dec 17.
Biochemical processes during bone regeneration can be analysed via quantification of peripheral serum cytokine levels. To date, serum levels of cytokines in patients treated with masquelet technique and patients with normal bone healing have not been compared. This comparison is supposed to deliver novel insights into the process of bone regeneration. Our aim was to validate this established method in the monitoring of bone regeneration after non-union treatment in masquelet technique.
Between 04/2008 and 01/2014 three groups were recruited: G1 (10 patients) with long bone non-unions, treated successfully with masquelet therapy, G2 (6 patients) with unsuccessful masquelet therapy and G3 (10 patients) with long bone fractures and normal bone healing. Peripheral blood samples were collected over a period of six months following a standardised time pattern in combination with clinical and radiologic follow up. TGF-ß1, PDGF-AB and IGF-1 were measured using commercially available immunoassays.
TGF-ß1 levels in G1 and G2 demonstrated a parallel and lower overall concentration over time compared to G3. G3 showed a significant TGF-ß1 peak 2 weeks after surgery compared to G1 (p=0.0054). PDGF-AB concentrations were always lower in G2 than in G1 and G3. G3 peaked at week 2 with a significant higher value than in G2 (p=0.0177). IGF-1 showed lower overall serum concentrations in G2 than in G1 and G3. G1 had a peak level during the fourth week of follow-up. Compared to G2 this peak was significant (p=0.0015).
This study shows that successful bone regeneration via masquelet technique only partially imitates cytokine expression of physiological bone healing. High expressions of IGF-1 correspond to a successful masquelet therapy while TGF-ß seems to play a minor role. These results assume that objective analysis of an effective non-union therapy with cytokine expression analysis is possible even with a small number of patients.
骨再生过程中的生化过程可通过外周血清细胞因子水平的定量分析来进行研究。迄今为止,尚未对采用Masquelet技术治疗的患者与骨愈合正常的患者的血清细胞因子水平进行比较。这种比较有望为骨再生过程提供新的见解。我们的目的是验证这种既定方法在监测Masquelet技术治疗骨不连后的骨再生情况中的有效性。
在2008年4月至2014年1月期间招募了三组患者:G1组(10例患者)为长骨骨不连,采用Masquelet疗法成功治疗;G2组(6例患者)为Masquelet疗法治疗失败;G3组(10例患者)为长骨骨折且骨愈合正常。按照标准化的时间模式,在六个月的时间内采集外周血样本,并结合临床和影像学随访。使用市售免疫测定法检测转化生长因子-β1(TGF-β1)、血小板衍生生长因子-AB(PDGF-AB)和胰岛素样生长因子-1(IGF-1)。
与G3组相比,G1组和G2组的TGF-β1水平随时间推移总体浓度呈平行且较低的状态。与G1组相比,G3组在术后2周出现显著的TGF-β1峰值(p = 0.0054)。G2组的PDGF-AB浓度始终低于G1组和G3组。G3组在第2周达到峰值,其值显著高于G2组(p = 0.0177)。G2组的IGF-1总体血清浓度低于G1组和G3组。G1组在随访的第四周达到峰值水平。与G2组相比,该峰值具有显著性(p = 0.0015)。
本研究表明,通过Masquelet技术成功实现骨再生仅部分模仿了生理性骨愈合的细胞因子表达。IGF-1的高表达对应着Masquelet疗法的成功,而TGF-β似乎起次要作用。这些结果表明,即使患者数量较少,通过细胞因子表达分析对有效的骨不连治疗进行客观分析也是可行的。