Application of BMP for reconstruction of bone defect after the removable of malignant bone tumor

在恶性骨肿瘤的治疗中，肿瘤的广泛切除会造成巨大的骨丢失。骨移植作为一种填充指骨小肿瘤等小缺损区的方法是一种有效的方法。但由于骨盆骨切除造成的巨大骨缺损，以前的方法并未成功重建。此外，恶性肿瘤患者接受过化疗或放射治疗，处于不利状态，因为这些治疗会对骨形成或修复造成负面影响。本研究旨在探讨抗癌药物对成骨反应的影响，以及对肿瘤尤其是骨盆骨肿瘤切除后理想的骨缺损区填充方法的改进。首先，通过植入由骨形态发生蛋白(BMP)和胶原载体组成的具有皮下成骨能力的微丸，研究了抗癌药物对成骨反应的影响。抗癌药物接受组…较少对照组在2~3周内以软骨成骨的方式成功成骨，抗癌药物组未见成熟骨形成，但有软骨样形成。接下来，我们利用大鼠股骨骨折模型考察了抗癌药物对骨折修复的影响。抗癌药物组骨折修复能力较弱。用抗血管内皮生长因子抗体进行免疫组织化学研究，抗癌药物组BMP颗粒周围的阳性染色较少，表明该药物对新骨形成所需的新血管形成有负面影响。最后制作了兔骨盆巨大骨缺损模型。作为充填缺损处的一种治疗方法，我们应用了三磷酸钙水门汀。单纯的糊剂并不能达到足够的愈合，但钛丝和糊剂的结合成功地有效地替代了骨缺损。较少

In a treatment of malignant bone tumor, huge loss of bone is caused by tumor wide resection. As a filling up the small defect such as small tumor of digital bone, bone transplant is a useful method. But huge bone defect caused by removal of the pelvic bone has not been successfully reconstructed by previous method. Furthermore, the patient suffering from malignant tumor has chemotherapy or radiation therapy, is in a disadvantage state because these treatment cause a negative affect for bone formation or repair. This study focused on the effect of the anti-cancer drug for bone forming reaction, and improvement of the ideal method for filling up the defect caused by tumor resection, especially pelvic bone tumor. First, we examined the influence of anti-cancer drug for bone-forming reaction by means of the implantation of pellet consisted of bone morphogenetic protein (BMP) and collagen carrier, which has an ability of forming subcutaneous bone. Anti cancer drug receiving group has less a … More bility of bone formation than control group; successful bone formation has been achieved in control group in 2 or 3 weeks by means of enchondral bone formation, on the other hand no mature bone formation but chondroid formation was seen in anti-cancer drug group. Next, we examined the influence of anti-cancer drug for fracture repair using rat femoral bone fracture model. Less ability for fracture repair was revealed in anti-cancer drug group. By an immunohistochemical study using anti-VEGF antibody, less positive staining around BMP pellet was seen in anti-cancer drug group, that indicates the drug had influenced a negative effect for new vascular formation which had been needed for new bone formation. Finally, we made the rabbit model bearing huge bone defect in pelvis. As a treatment of filling up the defect, we applied the triphosphate calcium cement paste. The paste alone did not cause the sufficient healing, but the combination of titanium wire and the paste caused successful and powerful replacement for the bone defect. Less