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Bone2009; 45(2); 267-273; doi: 10.1016/j.bone.2009.04.240

Differences in early osteogenesis and bone micro-architecture in anterior lumbar interbody fusion with rhBMP-2, equine bone protein extract, and autograft.

Abstract: To investigate the microstructural differences and responsible mechanisms in early bone formation in anterior lumbar interbody fusion (ALIF) in the spine using rhBMP-2 (INFUSE), equine bone protein extract (COLLOSS E) or autograft. Methods: Twelve Danish female landrace pigs underwent a 3-level ALIF procedure at L3-6. PEEK interbody cages packed with rhBMP-2, COLLOSS E, or autograft were inserted. The animals were divided into two groups of six, and observed for four and eight weeks postoperatively. MicroCT was performed for evaluation of microstructure of the bone within the cage. A mathematical finite element model was developed to investigate the aqueous behavior within the cages when exposed to external compressive forces. Results: At 4 weeks postoperative bone surface volume fraction (BS/TV) using rhBMP-2 was higher than with use of COLLOSS E and autograft, while trabecular thickness (Tb.Th.) was lower using rhBMP-2 at this time-point. At eight weeks BS/TV and trabecular number (Tb.N.) were still higher using rhBMP-2 than autograft and COLLOSS E. Connectivity density was significantly higher using rhBMP-2 than using autograft or COLLOSS E at both time-points. Between four- and eight-week time-points BV/TV and Tb.Th. rose while Tb.N. declined using rhBMP-2. The degree of anisotropy and the calculated amount of trabeculae with main direction along the spinal axis, were higher at four weeks using COLLOSS E. rhBMP-2 had the highest amount of trabeculae directed along the spinal axis at eight weeks. A change in main direction between four and eight weeks was observed for both autograft and rhBMP-2. The numerical results from the finite element model verify that significantly different flow pattern emerges as the boundary conditions are altered. At four weeks there was an evident correlation between trabecular orientation and flow pattern using rhBMP-2. Conclusions: This study reveals large differences in microstructure in the early osteogenesis and explains important mechanisms of early bone formation using rhBMP-2, COLLOSS E or autograft treatment. These differences might explain some of the unfortunate events reported such as edema, swelling, and excessive bone formation using different bone graft substitutes in spinal fusion procedures.
Publication Date: 2009-05-03 PubMed ID: 19398044DOI: 10.1016/j.bone.2009.04.240Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The study investigates the microstructural differences in early bone formation in anterior lumbar interbody fusion (ALIF) using different materials such as rhBMP-2 (INFUSE), equine bone protein extract (COLLOSS E) or autograft.

Study Methodology

  • The study involved twelve female Danish landrace pigs subjected to a 3-level ALIF procedure at vertebrae L3-6.
  • The procedure involved inserting interbody cages filled with either rhBMP-2, COLLOSS E, or an autograft.
  • The pigs were divided into two groups of six and observed for four and eight weeks post-operatively.
  • MicroCT scans were carried out to evaluate the microstructure of the bone developed within the cage.
  • A mathematical finite element model was developed to study the behavior of the aqueous within the cages when compressed.

Study Findings

  • Four weeks post-operation, bone surface volume fraction (BS/TV) was higher with rhBMP-2 compared to COLLOSS E and autograft, however, trabecular thickness (Tb.Th.) was lower with rhBMP-2.
  • Eight weeks post-operation, BS/TV and trabecular number (Tb.N.) were still higher with rhBMP-2 compared to the other treatments.
  • The connectivity density with rhBMP-2 was significantly higher than with autograft or COLLOSS E at both time-points.
  • The degree of anisotropy and calculated amount of trabeculae directed along the spinal axis were higher with COLLOSS E at four weeks but higher with rhBMP-2 at eight weeks.
  • A change in the main direction between the two time points was observed for both autograft and rhBMP-2.
  • The finite element model results suggest significant differences in flow pattern when the boundary conditions are changed.
  • There was an evident correlation between orientation of trabecular and flow pattern with rhBMP-2 treatment at four weeks.

Conclusions

  • The research exposed significant differences in microstructure during early bone formation using rhBMP-2, COLLOSS E or autograft treatment.
  • The differences highlighted may help explain unfortunate events, such as edema, swelling, and excessive bone formation, reported when using different bone graft substitutes in spinal fusion procedures.

Cite This Article

APA
Foldager C, Bendtsen M, Nygaard JV, Zou X, Bünger C. (2009). Differences in early osteogenesis and bone micro-architecture in anterior lumbar interbody fusion with rhBMP-2, equine bone protein extract, and autograft. Bone, 45(2), 267-273. https://doi.org/10.1016/j.bone.2009.04.240

Publication

ISSN: 1873-2763
NlmUniqueID: 8504048
Country: United States
Language: English
Volume: 45
Issue: 2
Pages: 267-273

Researcher Affiliations

Foldager, Casper
  • Orthopaedic Research Laboratory, Aarhus University Hospital, Noerrebrogade 44, building 1A, 8000 Aarhus C, Denmark. foldager@ki.au.dk
Bendtsen, Michael
    Nygaard, Jens Vinge
      Zou, Xuenong
        Bünger, Cody

          MeSH Terms

          • Animals
          • Bone Morphogenetic Protein 2
          • Bone Morphogenetic Proteins / pharmacology
          • Collagen / pharmacology
          • Finite Element Analysis
          • Horses
          • Lumbar Vertebrae / anatomy & histology
          • Lumbar Vertebrae / diagnostic imaging
          • Lumbar Vertebrae / drug effects
          • Models, Biological
          • Organ Size / drug effects
          • Osteogenesis / drug effects
          • Recombinant Proteins / pharmacology
          • Spinal Fusion
          • Sus scrofa
          • Transforming Growth Factor beta / pharmacology
          • Transplantation, Autologous
          • X-Ray Microtomography

          Citations

          This article has been cited 3 times.
          1. Sonmez Kaplan S, Sazak Ovecoglu H, Genc D, Akkoc T. TNF-α, IL-1B and IL-6 affect the differentiation ability of dental pulp stem cells.. BMC Oral Health 2023 Aug 11;23(1):555.
            doi: 10.1186/s12903-023-03288-1pubmed: 37568110google scholar: lookup
          2. Pastor MF, Floerkemeier T, Witte F, Nellesen J, Thorey F, Windhagen H, Wellmann M. Repetitive recombinant human bone morphogenetic protein 2 injections improve the callus microarchitecture and mechanical stiffness in a sheep model of distraction osteogenesis.. Orthop Rev (Pavia) 2012 Jan 2;4(1):e13.
            doi: 10.4081/or.2012.e13pubmed: 22577501google scholar: lookup
          3. Jensen J, Foldager CB, Jakobsen TV, Søballe K, Bünger C, Baas J. Use of carboxymethyl cellulose and collagen carrier with equine bone lyophilisate suggests late onset bone regenerative effect in a humerus drill defect - a pilot study in six sheep.. Open Orthop J 2010 May 11;4:181-7.
            doi: 10.2174/1874325001004010181pubmed: 20582241google scholar: lookup