Gruber Helen E, Ashraf Nomaan, Cox Michael D, Ingram Jane A, Templin Megan, Wattenbarger John Michael
Department of Orthopaedic Surgery.
Dickson Advanced Analytics, Carolinas Medical Center, Charlotte, NC.
J Pediatr Orthop. 2019 Oct;39(9):479-486. doi: 10.1097/BPO.0000000000001093.
Although physeal fractures and physeal bars can result in significant clinical consequences to growth and development of the injured physis, little orthopaedic research has focused upon this topic. Our objective was to extend a previously developed rat model to examine the immunohistochemical features following surgical application of techniques disrupting the physis.
Physes were surgically disrupted using fracture (control), epiphyseal scrape (ES), or epiphyseal drill (ED). After 1, 3, 6, 10, or 21 days, animals were euthanized, sites processed for histology and immunohistochemical localization of vascular endothelial growth factor (VEGF), Factor VIII, Sox-9, PTHrP (parathyroid hormone-related protein) and PTHrP-R (parathyroid hormone-related protein receptor) in resting, proliferative, and hypertrophic physeal zones. Incidence of physeal bars, vertical septa and islands within the metaphysis was quantified. Semiquantitative analysis of immunohistochemistry was performed.
Physeal bars, vertical septa, and displaced cartilage islands were present each of the surgical treatments. Fisher's exact test showed a statistically significant increase in the presence of physeal bars (P=0.002) and vertical septa (P=0.012) in the ED group at 10 and 21 days. Analysis of VEGF showed significant differences among the surgical treatments involving the resting zone, and the proliferative zone for days 1, 6, and 21 (P≤0.02) with greater mean scores present in the fracture (control) group, followed by the ED group; the lowest scores were present in the ES group. PTHrP-R immunolocalization showed significant differences among treatments in the hypertrophic zone at days 6 and 21 (P=0.022 and 0.044, respectively).
On the basis of the type of surgical treatment, results show significant differences in the presence of VEGF (reflecting the vascular bed) in the resting and proliferating zones at days 1, 6, and 21. VEGF localization was less abundant in the ED group (which had more physeal bars), suggesting that lack of vascular ingrowth plays a role in physeal bar formation.
Basic science data presented here provide insight into the importance of the various regions of the physis and its repair and continued growth after physeal fracture. We suggest that a better understanding of the cellular basis of physeal arrest following physeal fracture may have future relevance for the development of treatments to prevent or correct arrest.
尽管骺板骨折和骺板骨桥可对受伤骺板的生长发育造成严重临床后果，但骨科领域针对该主题的研究较少。我们的目的是扩展先前建立的大鼠模型，以研究破坏骺板的手术技术应用后的免疫组化特征。
采用骨折（对照组）、骨骺刮除术（ES）或骨骺钻孔术（ED）对骺板进行手术破坏。在术后1、3、6、10或21天，对动物实施安乐死，对手术部位进行组织学处理，并对静止、增殖和肥大骺板区域的血管内皮生长因子（VEGF）、凝血因子VIII、Sox-9、甲状旁腺激素相关蛋白（PTHrP）和甲状旁腺激素相关蛋白受体（PTHrP-R）进行免疫组化定位。对干骺端骺板骨桥、垂直骨嵴和骨岛的发生率进行量化。对免疫组化结果进行半定量分析。
每种手术治疗方式均出现了骺板骨桥、垂直骨嵴和移位的软骨岛。Fisher精确检验显示，在第10天和2l天，ED组的骺板骨桥（P = 0.002）和垂直骨嵴（P = 0.012）发生率有统计学意义的增加。VEGF分析显示，在涉及静止区以及第1、6和21天的增殖区的手术治疗之间存在显著差异（P≤0.02），骨折（对照）组的平均得分更高，其次是ED组；ES组得分最低。PTHrP-R免疫定位显示，在第6天和21天的肥大区，各治疗组之间存在显著差异（分别为P = 0.022和0.044）。
基于手术治疗方式，结果显示在第1、6和21天，静止区和增殖区的VEGF（反映血管床）存在显著差异。ED组（骺板骨桥更多）的VEGF定位较少，提示血管长入不足在骺板骨桥形成中起作用。
本文提供的基础科学数据有助于深入了解骺板各区域的重要性及其在骺板骨折后的修复和持续生长情况。我们认为，更好地理解骺板骨折后骺板停滞的细胞基础可能对预防或纠正停滞的治疗方法的开发具有未来意义。
