Distal tibial fracture repair in a neurofibromatosis type 1-deficient mouse treated with recombinant bone morphogenetic protein and a bisphosphonate
Distal tibial fracture repair in a neurofibromatosis type 1-deficient mouse treated with recombinant bone morphogenetic protein and a bisphosphonate
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DOI：
10.1302/0301-620x.93b8.25940
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发表时间：
2011-08-01
影响因子：
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通讯作者：
Little, D. G.
中科院分区：
文献类型：
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作者：
Schindeler, A.;Birke, O.;Little, D. G.
先天性胫骨假关节是1型神经纤维瘤病（NF 1）的一种罕见表现，但由于合成代谢不足和分解代谢过量而难以治疗。骨移植和最近的重组人骨形态发生蛋白（rhBMPs）已被确定为促合成代谢刺激物，具有改善手术后结果的潜力。作为一种额外的药物干预，我们描述了rhBMP-2和双膦酸盐唑来膦酸在NF 1缺陷型骨折修复小鼠模型中的联合使用。骨折为开放性骨折，特征为骨膜剥离。所有小鼠均接受10 μ g rhBMP-2，该rhBMP-2在骨折周围的羧甲基纤维素载体中递送作为合成代谢刺激。双膦酸盐治疗的小鼠也接受了5次0.02 mg/kg唑来膦酸的腹腔注射，当仅使用rhBMP而不使用唑来膦酸促进修复时，Nf 1（+/-）小鼠中75%的骨折在3周时仍然不愈合，而对照组为7%（p < 0.001）。术后全身使用唑来膦酸使骨折不愈合率减半至37.5%（p < 0.07）。这些数据支持了这样一个观点，即预防骨丢失联合促合成代谢可能改善先天性胫骨假胸合并NF 1患儿手术治疗后的结局。
Congenital pseudarthrosis of the tibia is an uncommon manifestation of neurofibromatosis type 1 (NF1), but one that remains difficult to treat due to anabolic deficiency and catabolic excess. Bone grafting and more recently recombinant human bone morphogenetic proteins (rhBMPs) have been identified as pro-anabolic stimuli with the potential to improve the outcome after surgery. As an additional pharmaceutical intervention, we describe the combined use of rhBMP-2 and the bisphosphonate zoledronic acid in a mouse model of NF1-deficient fracture repair.Fractures were generated in the distal tibiae of neurofibromatosis type 1-deficient (Nf1(+/-)) mice and control mice. Fractures were open and featured periosteal stripping. All mice received 10 mu g rhBMP-2 delivered in a carboxymethylcellulose carrier around the fracture as an anabolic stimulus. Bisphosphonate-treated mice also received five doses of 0.02 mg/kg zoledronic acid given by intraperitoneal injection.When only rhBMP but no zoledronic acid was used to promote repair, 75% of fractures in Nf1(+/-) mice remained ununited at three weeks compared with 7% of controls (p < 0.001). Systemic post-operative administration of zoledronic acid halved the rate of ununited fractures to 37.5% (p < 0.07).These data support the concept that preventing bone loss in combination with anabolic stimulation may improve the outcome following surgical treatment for children with congenital pseudarthoris of the tibia and NF1.