Comparison of a novel oxysterol molecule and rhBMP2 fusion rates in a rabbit posterolateral lumbar spine model.
Comparison of a novel oxysterol molecule and rhBMP2 fusion rates in a rabbit posterolateral lumbar spine model.
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DOI：
10.1016/j.spinee.2014.11.014
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发表时间：
2015-04-01
期刊：
影响因子：
--
通讯作者：
Parhami F
中科院分区：
文献类型：
--
作者：
Scott TP;Phan KH;Tian H;Suzuki A;Montgomery SR;Johnson JS;Atti E;Tetratis S;Pereira RC;Wang JC;Daubs MD;Stappenbeck F;Parhami F
腰椎融合术后骨不连率高达25%。骨形态发生蛋白-2（rhBMP-2）已被用作促进骨融合的生物学辅助物。然而，最近人们对BMP 2的关注。氧固醇133（Oxy 133）已被证明可促进啮齿类动物腰椎模型的良好融合率，并提供了rhBMP 2的潜在替代品。本研究的目的是使用后外侧腰椎兔脊柱融合模型在随机对照试验中比较rhBMP 2和Oxy 133的融合率。这是一项随机对照动物研究。24只雄性成年白色新西兰兔（3- 3.5 kg）在L4-L5进行双侧后外侧腰椎融合术。将家兔分为4组：对照组（A）、30 μg rhBMP 2组（B）、20 mg Oxy 133组（C）和60 mg Oxy 133组（D）。在第4周，通过荧光镜检查评价融合，在第8周处死家兔，通过X线片、手动触诊和microCT评价融合。Parhami博士是MAX BioPharma的创始人，Stappenbeck博士是化学总监，MAX BioPharma已从UCLA获得Oxy 133的许可权，两者都在这里介绍的技术中拥有经济利益。加州大学洛杉矶分校持有MAX BioPharma的股权。所有其他作者都没有利益冲突。本文报告的研究部分得到了NIH/NIAMS资助RO 1AR 059794的支持，部分得到了购买家兔并提供Oxy 133的MAX BioPharma的支持。8周时影像学分析的融合率为：A组40.0%，B组91.7%，C组91.7%，D组100%。通过处死后切除脊柱的手动触诊评估融合块，显示以下融合率：A组0%，B组83.3%，C组83.3%，D组90%。MicroCT扫描证实了这些发现。在兔模型中的这些发现表明，20 mg剂量和60 mg剂量的Oxy 133促进的融合与30 μg rhBMP 2诱导的融合相当，并且显著大于对照组。目前的研究结果证实，Oxy 133是一个有前途的候选人的治疗发展作为替代rhBMP 2，以促进脊柱融合。
The non-union rate following lumbar spinal fusion is as high as 25%. Bone morphogenetic protein-2 (rhBMP2) has been used as a biological adjunct to promote bony fusion. However, recently there have been concerns about BMP2. Oxysterol 133 (Oxy133) has been shown to promote excellent fusion rates in rodent lumbar spine models and offers a potential alternative to rhBMP2. The purpose of this study was to compare the fusion rate of rhBMP2 and Oxy133 in a randomized controlled trial using a posterolateral lumbar rabbit spinal fusion model. This was a randomized control animal study. Twenty-four male adult white New Zealand rabbits (3–3.5kg) underwent bilateral posterolateral lumbar spinal fusion at L4–L5. Rabbits were divided into 4 groups: control (A), 30 µg rhBMP2 (B), 20 mg Oxy133 (C), and 60 mg Oxy133 (D). At 4 weeks, fusion was evaluated by fluoroscopy, and at 8 weeks the rabbits were sacrificed and fusion was evaluated radiographically, by manual palpation, and with microCT. Dr. Parhami is a founder and Dr. Stappenbeck is the Director of Chemistry at MAX BioPharma, which has licensed the rights to Oxy133 from UCLA, both have financial interests in the technology presented here. UCLA holds equity in MAX BioPharma. All other authors have no conflicts of interest. Studies reported here were supported in part by the NIH/NIAMS grant RO1AR059794 and in part by MAX BioPharma that purchased the rabbits and provided Oxy133. Fusion rates by radiographic analysis at 8 weeks were: group A 40.0%, group B 91.7%, group C 91.7%, and group D 100%. Evaluation of fusion masses by manual palpation of excised spines after sacrifice showed the following fusion rates: group A 0%, group B 83.3%, group C 83.3%, and group D 90%. MicroCT scanning confirmed these findings. These findings in a rabbit model demonstrate that both 20 mg dose and 60 mg dose Oxy133 promote fusion that is equivalent to fusion induced by 30 µg rhBMP2 and significantly greater than the control group. The present findings confirm that Oxy133 is a promising candidate for therapeutic development as an alternative to rhBMP2 to promote spinal fusion.
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影响因子：
4.8
作者：
Garrett, Mark P.;Kakarla, Udaya K.;Sonntag, Volker K. H.
通讯作者：
Sonntag, Volker K. H.
影响因子：
6.2
作者：
Kha, HT;Basseri, B;Parhami, F
通讯作者：
Parhami, F
影响因子：
6.2
作者：
Montgomery, Scott R.;Nargizyan, Taya;Meliton, Vicente;Nachtergaele, Sigrid;Rohatgi, Rajat;Stappenbeck, Frank;Jung, Michael E.;Johnson, Jared S.;Aghdasi, Bayan;Tian, Haijun;Weintraub, Gil;Inoue, Hirokazu;Atti, Elisa;Tetradis, Sotirios;Pereira, Renata C.;Hokugo, Akishige;Alobaidaan, Raed;Tan, Yanlin;Hahn, Theodor J.;Wang, Jeffrey C.;Parhami, Farhad
通讯作者：
Parhami, Farhad
影响因子：
3
作者：
Itoh, H;Ebara, S;Takaoka, K
通讯作者：
Takaoka, K
影响因子：
4.5
作者：
Miyazaki, Masashi;Morishita, Yuichiro;Wang, Jeffrey C.
通讯作者：
Wang, Jeffrey C.