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重组人骨形态发生蛋白-2在维生素D缺乏大鼠模型中改善脊柱融合。

Recombinant Human Bone Morphogenetic Protein-2 Improves Spine Fusion in a Vitamin D-Deficient Rat Model.

作者信息

Patel Vikas V, Wuthrich Zachary R, Ortega Alicia, Ferguson Virginia L, Lindley Emily M

机构信息

Department of Orthopedics, Divisions of Spine Surgery and Research, University of Colorado Anschutz Medical Campus, Aurora, Colorado.

Department of Mechanical Engineering, University of Colorado Boulder, Boulder, Colorado.

出版信息

Int J Spine Surg. 2020 Oct;14(5):694-705. doi: 10.14444/7101. Epub 2020 Oct 19.

Abstract

BACKGROUND

The effects of vitamin D deficiency on spinal fusion are not well studied, nor are approaches to overcoming deficiency-related detrimental effects. The purpose of this study was to (1) evaluate the effects of vitamin D deficiency on spine fusion in a rat model, and (2) determine whether recombinant human bone morphogenetic protein-2 (rhBMP-2) can improve outcomes in deficient rats.

METHODS

Sprague-Dawley rats were assigned to a vitamin D group: vitamin D sufficient (14), vitamin D deficient (16), vitamin D postoperative rescue (15). Posterolateral fusion was performed at L3-4 and L5-6, with one level receiving rhBMP-2 and the other allograft. Following 6 weeks, the spines were harvested for micro-computed tomography (micro-CT) and histological analyses. Fusion was assessed via manual palpation and micro-CT assessment. Micro-CT images were analyzed for bone microarchitecture in intact L5 vertebral bodies and within fused bone masses treated with rhBMP-2.

RESULTS

There were no significant effects of vitamin D status on fusion assessments. However, the microarchitecture of native bone in the intact L5 vertebral bodies of vitamin D-sufficient rats showed significantly greater trabecular thickness ( < .001) and bone volume fraction ( < .001), with decreased trabecular spacing ( < .001), than that of vitamin D-deficient rats. Fusion masses of rhBMP-2 levels also showed significant effects of vitamin D supplementation on both bone volume fraction and trabecular thickness. Histological analysis confirmed that robust bone formation was observed in rhBMP-2-treated fusions, but not in fusion levels treated with allograft.

CONCLUSIONS

Overall, vitamin D deficiency decreased trabecular bone microarchitecture, and treatment with rhBMP-2 improved outcomes across all vitamin D groups.

CLINICAL RELEVANCE

Given the prevalence of vitamin D deficiency in spine surgery patients, vitamin D supplementation may be a cost-effective method for reducing the risk of pseudoarthrosis.

摘要

背景

维生素D缺乏对脊柱融合的影响尚未得到充分研究,克服与缺乏相关的有害影响的方法也未得到充分研究。本研究的目的是:(1)在大鼠模型中评估维生素D缺乏对脊柱融合的影响;(2)确定重组人骨形态发生蛋白-2(rhBMP-2)是否能改善维生素D缺乏大鼠的结局。

方法

将Sprague-Dawley大鼠分为维生素D组:维生素D充足组(14只)、维生素D缺乏组(16只)、维生素D术后补充组(15只)。在L3-4和L5-6节段进行后外侧融合,一个节段接受rhBMP-2治疗,另一个节段接受同种异体骨移植。6周后,取出脊柱进行微型计算机断层扫描(micro-CT)和组织学分析。通过手动触诊和micro-CT评估来评估融合情况。对完整L5椎体和用rhBMP-2治疗的融合骨块内的骨微结构进行micro-CT图像分析。

结果

维生素D状态对融合评估没有显著影响。然而,与维生素D缺乏的大鼠相比,维生素D充足的大鼠完整L5椎体的天然骨微结构显示,其小梁厚度(P<0.001)和骨体积分数(P<0.001)显著更大,小梁间距减小(P<0.001)。rhBMP-2治疗节段的融合块也显示,补充维生素D对骨体积分数和小梁厚度均有显著影响。组织学分析证实,在rhBMP-2治疗的融合中观察到了强劲的骨形成,但在同种异体骨移植治疗的融合节段中未观察到。

结论

总体而言,维生素D缺乏会降低小梁骨微结构,而rhBMP-2治疗可改善所有维生素D组的结局。

临床意义

鉴于脊柱手术患者中维生素D缺乏的普遍性,补充维生素D可能是降低假关节风险的一种经济有效的方法。

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