Effects of Estrogen on Fracture Healing in Mice

Effects of Estrogen on Fracture Healing in Mice
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DOI:
10.1097/ta.0b013e3181c4544d
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发表时间:
2010-11-01
影响因子:
--
通讯作者:
Amling, Michael
Amling, Michael
中科院分区:
其他
文献类型:
--
作者:
Beil, Frank Timo;Barvencik, Florian;Amling, Michael

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背景:骨折愈合是一个复杂而连续的过程。骨折愈合的一个重要步骤是骨痂重塑。雌激素缺乏会增加破骨细胞骨吸收,而雌激素替代可以逆转这一影响。因此,我们的研究目的是分析雌激素缺乏和雌激素治疗是否会分别影响骨折愈合过程中骨痂的重塑。方法:采用断头台样骨折装置对10周龄C57BL/6小鼠进行标准化股骨骨折。小鼠被分成三组。第一组连续给予雌激素。第二组采用卵巢切除术(OVX)建立雌激素缺乏模型。对照组不给予特殊治疗。在骨折愈合的不同阶段,进行接触x线,显微计算机断层扫描,组织学和生物力学分析。结果:我们观察到,在骨折愈合的早期阶段,OVX导致骨膜骨痂形成受损。与对照组相比,软骨细胞面积减小,后续矿化不明显。在骨折愈合后期,OVX小鼠表现出薄而多孔的皮质。与之形成鲜明对比的是,雌激素治疗可促进骨折愈合。软骨细胞面积增大,愈伤组织矿化增加,新皮层增厚。生物力学试验证实了雌激素对生物力学能力恢复的有益作用。结论:雌激素在骨折愈合的各个阶段都起着重要的作用。雌激素的应用至少对小鼠长骨骨折愈合有促进作用。
Background: Fracture healing is a complex and sequential process. One important step in fracture healing is callus remodeling. Estrogen deficiency is known to increase osteoclast bone resorption, whereas estrogen replacement can reverse this effect. Therefore, the aim of our study was to analyze whether estrogen deficiency and estrogen treatment, respectively, would affect callus remodeling in the fracture healing process.Methods: Standardized femoral fractures were produced in 10 weeks old C57BL/6 mice using a guillotine-like fracture device. Mice were separated into three groups. The first group obtained a continuous administration of estrogen. Ovariectomy (OVX) was performed in the second group to generate an estrogen-deficiency model. The control group obtained no special treatment. At different stages of fracture healing, contact X-ray, micro-computed tomography, histologic, and biomechanical analyses were performed.Results: We observed that, in early stages of fracture healing, OVX leads to an impaired periosteal callus formation. When compared with the control group, chondrocytes area was decreased, and the subsequent mineralization was less distinctive. In the late stage of fracture healing, the OVX mice showed a thin and porous cortex. In sharp contrast, estrogen treatment led to an enhanced fracture healing. Chondrocyte areas were larger, callus mineralization was increased, and the neocortex was thicker. Biomechanical testing confirmed the beneficial effects of estrogen on restoration of biomechanical competence.Conclusion: These results indicate that estrogen seems to be an important factor in all stages of fracture healing. The application of estrogens enhances fracture healing of long bones at least in mice.