Kannan Abhishek, Minardi Silvia, Ellenbogen David J, Hallman Mitchell J, Greene Allison C, Yamaguchi Jonathan T, Plantz Mark A, Jeong Soyoen, Sana Kennedy C, Shah Vivek, Yun Chawon, Hsu Erin L, Hsu Wellington K
Department of Orthopaedic Surgery Northwestern University Chicago Illinois USA.
Center for Regenerative Nanomedicine Simpson Querrey Institute Chicago Illinois USA.
JOR Spine. 2021 Dec 13;4(4):e1177. doi: 10.1002/jsp2.1177. eCollection 2021 Dec.
Local steroid administration during anterior cervical spine surgery has been shown to improve postoperative dysphagia. However, concerns over potential complications remain. This study aims to evaluate the effect of local steroid administration on bone regeneration and spine fusion in a preclinical model, as well as the impact on osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in a 3D culture system.
Forty-five rats underwent bilateral L4-L5 posterolateral lumbar fusion (PLF) utilizing local delivery of low-dose recombinant human bone morphogenetic protein-2 (rhBMP-2; 0.5 μg/implant). Rats were divided into three groups: no steroid (control), low dose (0.5 mg/kg), and high dose (2.5 mg/kg) of triamcinolone. Bone growth and fusion were assessed using radiography, blinded manual palpation, and micro-CT analysis and were visualized by histology. The impact of triamcinolone exposure on osteogenic differentiation of hBM-MSCs was evaluated by gene expression analysis, alkaline phosphatase activity assay, and alizarin red staining.
No significant differences in fusion scores or rates were seen in the low- or high-dose steroid treatment groups relative to untreated controls. Quantification of new bone formation via micro-CT imaging revealed no significant between-group differences in the volume of newly regenerated bone. Triamcinolone also had no negative impact on pro-osteogenic gene transcript levels, and ALP activity was enhanced in the presence of triamcinolone. Mineral deposition appeared comparable in cultures grown with and without triamcinolone.
Local steroid application does not seem to inhibit rhBMP-2-mediated spine fusion in rats, though our study may not be adequately powered to detect differences in fusion as measured by manual palpation or bone volume as measured by micro-CT. These findings suggest that local triamcinolone may not increase pseudarthrosis in spine fusion procedures. Further large animal and clinical studies to verify its safety and efficacy are warranted.
颈椎前路手术中局部应用类固醇已被证明可改善术后吞咽困难。然而,对潜在并发症的担忧依然存在。本研究旨在评估在临床前模型中局部应用类固醇对骨再生和脊柱融合的影响,以及在三维培养系统中对人骨髓间充质干细胞(hBM-MSCs)成骨分化的影响。
45只大鼠接受双侧L4-L5后外侧腰椎融合术(PLF),采用局部递送低剂量重组人骨形态发生蛋白-2(rhBMP-2;0.5μg/植入物)。大鼠分为三组:无类固醇组(对照组)、低剂量(0.5mg/kg)和高剂量(2.5mg/kg)曲安奈德组。使用X线摄影、盲法手动触诊和显微CT分析评估骨生长和融合情况,并通过组织学观察。通过基因表达分析、碱性磷酸酶活性测定和茜素红染色评估曲安奈德暴露对hBM-MSCs成骨分化的影响。
与未治疗的对照组相比,低剂量或高剂量类固醇治疗组的融合评分或融合率无显著差异。通过显微CT成像对新骨形成进行定量分析,结果显示新再生骨体积在组间无显著差异。曲安奈德对促骨生成基因转录水平也没有负面影响,并且在有曲安奈德存在的情况下碱性磷酸酶活性增强。在有和没有曲安奈德的培养物中,矿物质沉积似乎相当。
局部应用类固醇似乎不会抑制大鼠中rhBMP-2介导的脊柱融合,尽管我们的研究可能没有足够的效力来检测通过手动触诊测量的融合差异或通过显微CT测量的骨体积差异。这些发现表明,局部应用曲安奈德可能不会增加脊柱融合手术中的假关节形成。有必要进行进一步的大型动物和临床研究以验证其安全性和有效性。