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Research ArticleLumbar Spine

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

Vikas V. Patel, Zachary R. Wuthrich, Alicia Ortega, Virginia L. Ferguson and Emily M. Lindley
International Journal of Spine Surgery October 2020, 7101; DOI: https://doi.org/10.14444/7101
Vikas V. Patel
1Department of Orthopedics, Divisions of Spine Surgery and Research, University of Colorado Anschutz Medical Campus, Aurora, Colorado
MD
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Zachary R. Wuthrich
1Department of Orthopedics, Divisions of Spine Surgery and Research, University of Colorado Anschutz Medical Campus, Aurora, Colorado
BS
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Alicia Ortega
2Department of Mechanical Engineering, University of Colorado Boulder, Boulder, Colorado
PhD
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Virginia L. Ferguson
2Department of Mechanical Engineering, University of Colorado Boulder, Boulder, Colorado
PhD
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Emily M. Lindley
1Department of Orthopedics, Divisions of Spine Surgery and Research, University of Colorado Anschutz Medical Campus, Aurora, Colorado
PhD
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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.

  • vitamin D
  • lumbar spine
  • fusion
  • rat model
  • rhBMP-2
  • micro-CT
  • allograft

Footnotes

  • Disclosures and COI: The research described in this manuscript was approved by our local Institutional Animal Care and Use Committee. The institution of one or more of the authors (EML, VVP) has received funding from Medtronic Inc, related to this work.

  • This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2020 ISASS.
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International Journal of Spine Surgery: 19 (S2)
International Journal of Spine Surgery
Vol. 19, Issue S2
1 Apr 2025
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Recombinant Human Bone Morphogenetic Protein–2 Improves Spine Fusion in a Vitamin D–Deficient Rat Model
Vikas V. Patel, Zachary R. Wuthrich, Alicia Ortega, Virginia L. Ferguson, Emily M. Lindley
International Journal of Spine Surgery Oct 2020, 7101; DOI: 10.14444/7101

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Recombinant Human Bone Morphogenetic Protein–2 Improves Spine Fusion in a Vitamin D–Deficient Rat Model
Vikas V. Patel, Zachary R. Wuthrich, Alicia Ortega, Virginia L. Ferguson, Emily M. Lindley
International Journal of Spine Surgery Oct 2020, 7101; DOI: 10.14444/7101
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  • Recovery Trajectories After Lumbar Fusion Stratified by Baseline Patient-Reported Outcomes Measurement Information System Physical Function Disability Levels
  • Safety and Viability of Anterior Lumbar Interbody Fusion in Complex Revision Lumbar Spine Surgeries: Insights From a Case Series of 135 Patients on Transforaminal Lumbar Interbody Fusion/Posterior Lumbar Interbody Fusion Cage Removal
  • Effects of Body Mass Index on Spondylolisthesis Surgery and Associated Patient-Reported Outcomes: A Retrospective Review
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Keywords

  • vitamin D
  • lumbar spine
  • fusion
  • rat model
  • rhBMP-2
  • micro-CT
  • allograft

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