Division of Orthopaedic Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
J Orthop Res. 2014 Oct;32(10):1252-63. doi: 10.1002/jor.22661. Epub 2014 Jun 25.
The goal of soft tissue sarcoma management in the extremities is limb preservation, often combining surgery and external beam radiation. In patients who have undergone this therapy in the thigh, pathologic fracture is a serious, late complication. Non-union rates of 80-90% persist. No reliable biologic solution exists. A rat model combining one 18 Gy dose of radiation and diaphyseal periosteal excision reliably generates atrophic non-union of femoral fractures. We hypothesized that augmentation with OP-1 would increase union rate. Female Sprague-Dawley retired breeder rats were randomized to Control, Disease (external beam radiotherapy and periosteal stripping), Control + OP-1 (80 µg) and Disease + OP-1 groups. Animals underwent prophylactic fixation and controlled left femur fracture. Twenty-eight, 35, and 42 days post-fracture were end-points. Femora were analyzed using MicroCT, Back Scattered Electron Microscopy, and Histomorphometry. We observed a 2% union rate in the Disease groups (±OP-1 treatment). The union rate in Control groups was 97%. MicroCT demonstrated a lack of callus volume in Disease groups. Heterotopic ossification was observed in some OP-1 treated animals. The ineffectiveness of OP-1 in stimulating fracture union in this model suggests the endogenous repair mechanism has been compromised beyond the capabilities of osteoinductive biologics.
四肢软组织肉瘤的治疗目标是保留肢体，通常结合手术和外照射放疗。在接受大腿部位这种治疗的患者中，病理性骨折是一种严重的、晚期并发症。非愈合率仍高达 80%-90%。目前尚无可靠的生物学解决方案。我们建立了一个大鼠模型，通过单次 18Gy 剂量的辐射和骨干骨膜切除，可靠地导致股骨骨折出现萎缩性不愈合。我们假设使用 OP-1 进行增强会增加愈合率。雌性 Sprague-Dawley 退休种鼠被随机分为对照组、疾病组（外照射放疗和骨膜剥离）、对照组+OP-1（80µg）和疾病组+OP-1 组。动物接受预防性固定和控制左侧股骨骨折。骨折后 28、35 和 42 天为终点。使用 MicroCT、背散射电子显微镜和组织形态计量学对股骨进行分析。我们观察到疾病组的愈合率为 2%（±OP-1 治疗）。对照组的愈合率为 97%。MicroCT 显示疾病组的骨痂体积缺乏。一些接受 OP-1 治疗的动物出现异位骨化。OP-1 在该模型中刺激骨折愈合的无效性表明，内源性修复机制已受损，超出了骨诱导生物制剂的能力。
