Würzler K K, DeWeese T L, Sebald W, Reddi A H
Department of Orthopaedic Surgery, University of California, Davis, Sacramento 95817, USA.
J Craniofac Surg. 1998 Mar;9(2):131-7. doi: 10.1097/00001665-199803000-00009.
Radiotherapy of head and neck tumors very often results in impaired healing of craniomaxillofacial bones in the vicinity. Management of radionecrosis of bones after radiotherapy is an important clinical challenge. Bone morphogenetic proteins (BMPs) induce new bone differentiation. The aim of this study is to investigate the potential of BMPs in ameliorating radiation-induced impaired bone repair. Two 3-mm diameter defects were created in the calvaria of rats. The defects were treated with different doses of recombinant human (rh) BMP-2 using collagen type I as a carrier. Irradiation with a single dose of 1,200 rad was performed 2 or 7 days preoperatively. Unirradiated animals served as controls. New bone formation was assessed by quantitation of radiographs of the calvaria and histology on day 21 after surgery. Untreated, unirradiated defects showed a spontaneous osseous regeneration of 90 +/- 7% of the defect area within 21 days. Irradiation of the site (1,200 rad 2 days preoperatively) resulted in a profound decrease in the bone fill of the untreated defect (5 +/- 2%). Recombinant human BMP-2 in soluble collagen type I carrier delivered to the defect resulted in a significant increase of new bone formation (34 +/- 14%, P < 0.01 for 25 micrograms rhBMP-2; 77 +/- 19% for 35 micrograms rhBMP-2, P < 0.01). Type I collagen carrier alone resulted in only 7 +/- 2% healing. In conclusion, radiation-induced impairment of calvarial repair can be overcome by rhBMP-2. Thus, the concept of BMP-2-induced regeneration has potential applications in reconstructive craniomaxillofacial surgery after irradiation.
头颈部肿瘤放疗常常导致附近颅颌面骨愈合受损。放疗后骨放射性坏死的处理是一项重要的临床挑战。骨形态发生蛋白（BMPs）可诱导新骨分化。本研究旨在探讨BMPs改善辐射诱导的骨修复受损的潜力。在大鼠颅骨上制造两个直径3毫米的缺损。使用I型胶原作为载体，用不同剂量的重组人（rh）BMP-2处理缺损。术前2天或7天进行单次1200拉德的照射。未照射的动物作为对照。术后21天通过颅骨X线片定量分析和组织学评估新骨形成情况。未经处理、未照射的缺损在21天内缺损面积的自发骨再生率为90±7%。对该部位进行照射（术前2天1200拉德）导致未处理缺损的骨填充率大幅下降（5±2%）。将可溶性I型胶原载体中的重组人BMP-2递送至缺损处可显著增加新骨形成（25微克rhBMP-2时为34±14%，P<0.01；35微克rhBMP-2时为77±19%，P<0.01）。单独的I型胶原载体仅导致7±2%的愈合。总之，rhBMP-2可克服辐射诱导的颅骨修复受损。因此，BMP-2诱导再生的概念在放疗后的颅颌面重建手术中有潜在应用。
