Background

Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication associated with antiresorptive and antiangiogenic medications, of which impaired angiogenesis is a key pathological alteration. Since Magnesium (Mg)-based implants possess proangiogenic effects, we hypothesized that the biodegradable Mg implant could alleviate the development of MRONJ via enhancing angiogenesis.

Methods

MRONJ model was established and divided into the Veh ​+ ​Ti group (Vehicle-treated rat, with Titanium (Ti) implant), BP ​+ ​Ti group (Bisphosphonate (BP)-treated rat, with Ti implant), BP ​+ ​Mg group (BP-treated rat, with Mg implant), BP ​+ ​Mg ​+ ​SU5416 group (BP-treated rat, with Mg implant and vascular endothelial growth factor (VEGF) receptor-2 inhibitor), BP ​+ ​Mg ​+ ​BIBN group (BP-treated rat, with Mg implant and calcitonin gene-related peptide (CGRP) receptor antagonist), and BP ​+ ​Mg ​+ ​SU5416+BIBN group (BP-treated rat, with Mg implant and VEGF receptor-2 inhibitor and CGRP receptor antagonist). The occurrence of MRONJ, alveolar bone necrosis, new bone formation and vessel formation were assessed by histomorphometry, immunohistochemistry, and micro-CT analysis.

Results

Eight weeks after surgery, the BP ​+ ​Mg group had significantly reduced occurrence of MRONJ-like lesion and histological osteonecrosis, increased bone microstructural parameters, and increased expressions of VEGFA and CGRP, than the BP ​+ ​Ti group. By simultaneously blocking VEGF receptor-2 and CGRP receptor, the vessel volume and new bone formation in the BP ​+ ​Mg group were significantly decreased, meanwhile the occurrence of MRONJ-like lesion and histological bone necrosis were significantly increased.

Conclusion

Biodegradable Mg implant could alleviate the development of MRONJ-like lesion, possibly via upregulating VEGF- and CGRP-mediated angiogenesis. Mg-based implants have the translational potential to be developed as a novel internal fixation device for patients with the risk of MRONJ.

The Translational potential of this article

This work reports a biodegradable Mg implant which ameliorates the development of MRONJ-like lesions possibly due to its angiogenic property. Mg-based implants have the potential to be developed as a novel internal fixation device for patients at the risk of MRONJ.

中文翻译：

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可生物降解的镁植入物增强血管生成并减轻大鼠下颌的药物相关性骨坏死

背景

药物相关性颌骨坏死 (MRONJ) 是与抗再吸收和抗血管生成药物相关的严重并发症，其中血管生成受损是关键的病理改变。由于基于镁 (Mg) 的植入物具有促血管生成作用，我们假设可生物降解的镁植入物可以通过增强血管生成来缓解 MRONJ 的发展。

方法

建立MRONJ模型并将其分为Veh​+​​Ti组（Vehicle-treatment大鼠，植入钛（Ti））、BP​+​Ti组（双膦酸盐（BP）治疗大鼠，植入Ti）、BP​​​ +​Mg组（BP处理的大鼠，植入Mg），BP​+​Mg​+​SU5416组（BP处理的大鼠，植入Mg和血管内皮生长因子（VEGF）受体2抑制剂），BP​​​ +​Mg​+​BIBN组（BP处理的大鼠，Mg植入物和降钙素基因相关肽（CGRP）受体拮抗剂）和BP​+​Mg​+​SU5416+BIBN组（BP处理的大鼠，具有Mg 植入物和 VEGF 受体 2 抑制剂和 CGRP 受体拮抗剂）。通过组织形态计量学、免疫组织化学和显微CT分析评估MRONJ的发生、牙槽骨坏死、新骨形成和血管形成。

结果

术后8周，与BP + Ti组相比，BP + ​Mg组MRONJ样病变和组织学骨坏死的发生率显着降低，骨显微结构参数增加，VEGFA和CGRP表达增加。通过同时阻断 VEGF 受体 2 和 CGRP 受体，BP + Mg 组的血管体积和新骨形成显着减少，同时 MRONJ 样病变和组织学骨坏死的发生率显着增加。

结论

可生物降解的镁植入物可以通过上调 VEGF 和 CGRP 介导的血管生成来减轻 MRONJ 样病变的发展。镁基植入物具有转化潜力，可作为一种新型内固定装置，用于有 MRONJ 风险的患者。

本文的转化潜力

这项工作报告了一种可生物降解的镁植入物，它可能由于其血管生成特性而改善了 MRONJ 样病变的发展。镁基植入物有可能被开发为一种新型内固定装置，用于有 MRONJ 风险的患者。