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唑来膦酸对小鼠模型中使用脱矿骨基质进行后外侧脊柱融合时新骨形成的局部作用。

Local effect of zoledronic acid on new bone formation in posterolateral spinal fusion with demineralized bone matrix in a murine model.

作者信息

Zwolak Pawel, Farei-Campagna Jan, Jentzsch Thorsten, von Rechenberg Brigitte, Werner Clément M

机构信息

Department of Trauma Surgery, University Hospital of Zurich, Rämistrasse 100, 8006, Zurich, Switzerland.

Vetsuisse Faculty, University of Zurich, Winterthurerstr. 260, 8057, Zurich, Switzerland.

出版信息

Arch Orthop Trauma Surg. 2018 Jan;138(1):13-18. doi: 10.1007/s00402-017-2818-4. Epub 2017 Oct 10.

Abstract

BACKGROUND

Posterolateral spinal fusion is a common orthopaedic surgery performed to treat degenerative and traumatic deformities of the spinal column. In posteriolateral spinal fusion, different osteoinductive demineralized bone matrix products have been previously investigated. We evaluated the effect of locally applied zoledronic acid in combination with commercially available demineralized bone matrix putty on new bone formation in posterolateral spinal fusion in a murine in vivo model.

METHODS

A posterolateral sacral spine fusion in murine model was used to evaluate the new bone formation. We used the sacral spine fusion model to model the clinical situation in which a bone graft or demineralized bone matrix is applied after dorsal instrumentation of the spine. In our study, group 1 received decortications only (n = 10), group 2 received decortication, and absorbable collagen sponge carrier, group 3 received decortication and absorbable collagen sponge carrier with zoledronic acid in dose 10 µg, group 4 received demineralized bone matrix putty (DBM putty) plus decortication (n = 10), and group 5 received DBM putty, decortication and locally applied zoledronic acid in dose 10 µg. Imaging was performed using MicroCT for new bone formation assessment. Also, murine spines were harvested for histopathological analysis 10 weeks after surgery.

RESULTS

The surgery performed through midline posterior approach was reproducible. In group with decortication alone there was no new bone formation. Application of demineralized bone matrix putty alone produced new bone formation which bridged the S1-S4 laminae. Local application of zoledronic acid to demineralized bone matrix putty resulted in significant increase of new bone formation as compared to demineralized bone matrix putty group alone.

CONCLUSIONS

A single local application of zoledronic acid with DBM putty during posterolateral fusion in sacral murine spine model increased significantly new bone formation in situ in our model. Therefore, our results justify further investigations to potentially use local application of zoledronic acid in future clinical studies.

摘要

背景

后外侧脊柱融合术是一种常见的骨科手术,用于治疗脊柱的退行性和创伤性畸形。在以往的后外侧脊柱融合术中,已经对不同的具有骨诱导作用的脱矿骨基质产品进行了研究。我们在小鼠体内模型中评估了局部应用唑来膦酸联合市售脱矿骨基质糊剂对后外侧脊柱融合术中新骨形成的影响。

方法

采用小鼠后外侧骶骨脊柱融合模型评估新骨形成情况。我们使用骶骨脊柱融合模型来模拟脊柱后路内固定术后应用骨移植或脱矿骨基质的临床情况。在我们的研究中,第1组仅接受去皮质术(n = 10),第2组接受去皮质术和可吸收胶原海绵载体,第3组接受去皮质术和剂量为10 μg的含唑来膦酸的可吸收胶原海绵载体,第4组接受脱矿骨基质糊剂(DBM糊剂)加去皮质术(n = 10),第5组接受DBM糊剂、去皮质术和剂量为10 μg的局部应用唑来膦酸。使用微型计算机断层扫描(MicroCT)进行成像以评估新骨形成情况。此外,在手术后10周采集小鼠脊柱进行组织病理学分析。

结果

通过中线后入路进行的手术具有可重复性。仅接受去皮质术的组没有新骨形成。单独应用脱矿骨基质糊剂产生了连接S1 - S4椎板的新骨形成。与单独的脱矿骨基质糊剂组相比,在脱矿骨基质糊剂中局部应用唑来膦酸导致新骨形成显著增加。

结论

在骶部小鼠脊柱模型的后外侧融合术中,将唑来膦酸与DBM糊剂单次局部应用可显著增加我们模型中原位新骨形成。因此,我们的结果证明有必要进一步研究,以便在未来的临床研究中可能使用局部应用唑来膦酸。

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