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

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 (P < .001) and bone volume fraction (P < .001), with decreased trabecular spacing (P < .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.

Keywords: allograft; fusion; lumbar spine; micro-CT; rat model; rhBMP-2; vitamin D.