The challenges of promoting osteogenesis in segmental bone defects and osteoporosis.
The challenges of promoting osteogenesis in segmental bone defects and osteoporosis.
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DOI：
10.1002/jor.23845
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Goodrich LR
中科院分区：
文献类型：
--
作者：
Ball AN;Donahue SW;Wojda SJ;McIlwraith CW;Kawcak CE;Ehrhart N;Goodrich LR
复杂骨愈合情况的常规临床管理继续导致5-10%的骨折形成骨不连。此外，人口老龄化和骨质疏松相关骨折的患病率需要进一步探索新的方法来增加这一特殊人群的骨生成。本文综述了目前的临床模式，以及正在进行的临床和临床前研究，以促进节段性骨缺损，延迟愈合和骨质疏松症的成骨。总之，骨折修复的动物模型通常是小动物，因为历史上重要的大型动物模型，如狗，继续作为伴侣动物获得青睐。与人类的骨折修复相比，小型啮齿动物有很好的局限性，并且几乎没有相似之处。研究设计、研究数量和资金的可用性继续限制大型动物研究。用rhBMP-2进行骨诱导可导致稳健的骨形成，尽管由于骨矿物质质量差，长期质量受到严格审查。PTH 1-34是唯一FDA批准的骨合成代谢治疗，以防止骨质疏松性骨折。仅限于2年的临床使用，PTH 1-34在系统的人类临床研究中应用于病理性骨折时，进一步受到剂量相关模糊性和不一致结果的困扰。PTH 1-34局部应用于骨缺损的动物数据有限。基因疗法继续在研究人员中流行，以增加骨愈合。非整合病毒载体和基因修饰治疗细胞的靶向凋亡是一个正在进行的研究领域。最后，祖细胞疗法和患者方治疗的内容变化（例如，PRP和BMAC）正在研究中。
Conventional clinical management of complex bone healing scenarios continues to result in 5–10% of fractures forming non-unions. Additionally, the aging population and prevalence of osteoporosis-related fractures necessitate the further exploration of novel ways to augment osteogenesis in this special population. This review focuses on the current clinical modalities available, and the ongoing clinical and pre-clinical research to promote osteogenesis in segmental bone defects, delayed unions, and osteoporosis. In summary, animal models of fracture repair are often small animals as historically significant large animal models, like the dog, continue to gain favor as companion animals. Small rodents have well-documented limitations in comparing to fracture repair in humans, and few similarities exist. Study design, number of studies, and availability of funding continue to limit large animal studies. Osteoinduction with rhBMP-2 results in robust bone formation, although long-term quality is scrutinized due to poor bone mineral quality. PTH 1–34 is the only FDA approved osteo-anabolic treatment to prevent osteoporotic fractures. Limited to 2 years of clinical use, PTH 1–34 has further been plagued by dose-related ambiguities and inconsistent results when applied to pathologic fractures in systematic human clinical studies. There is limited animal data of PTH 1–34 applied locally to bone defects. Gene therapy continues to gain popularity among researchers to augment bone healing. Non-integrating viral vectors and targeted apoptosis of genetically modified therapeutic cells is an ongoing area of research. Finally, progenitor cell therapies and the content variation of patient-side treatments (e.g., PRP and BMAC) are being studied.
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影响因子：
4.6
作者：
Billing AM;Ben Hamidane H;Dib SS;Cotton RJ;Bhagwat AM;Kumar P;Hayat S;Yousri NA;Goswami N;Suhre K;Rafii A;Graumann J
通讯作者：
Graumann J
影响因子：
3
作者：
Burkus, JK;Sandhu, HS;Gornet, MF
通讯作者：
Gornet, MF
影响因子：
4.2
作者：
Daugaard, Henrik;Elmengaard, Brian;Andreassen, Troels;Bechtold, Joan;Lamberg, Anders;Soballe, Kjeld
通讯作者：
Soballe, Kjeld
影响因子：
6.2
作者：
Andreassen, TT;Ejersted, C;Oxlund, H
通讯作者：
Oxlund, H
影响因子：
5.1
作者：
Alaee, F.;Sugiyama, O.;Lieberman, J. R.
通讯作者：
Lieberman, J. R.