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Spine2008; 33(25); 2683-2690; doi: 10.1097/BRS.0b013e31817fce91

ISSLS prize winner: positron emission tomography and magnetic resonance imaging for monitoring interbody fusion with equine bone protein extract, recombinant human bone morphogenetic protein-2, and autograft.

Abstract: Prospective and randomized experimental study with anterior lumbar interbody fusion in a porcine model. Objective: To assess the early time-course of spinal fusion with equine bone protein extract (COLLOSS E), recombinant human bone morphogenetic protein-2 (rhBMP-2), and autograft using quantitative methods of positron emission tomography (PET)/computed tomography and magnetic resonance imaging (MRI). Background: Different growth and differentiation factors are currently being used for inducing bone formation in spinal fusion. However, the mechanisms and time-course of bone formation using these graft substitutes remain less known. Methods: Eighteen female Danish landrace pigs underwent a 3-level anterior lumbar interbody fusion procedure from L3-L6. A PEEK cage, packed with COLLOSS E, rhBMP-2, or autograft, was randomly placed. Each group of 6 pigs was observed for 2, 4, or 8 weeks, respectively. F PET/computed tomography and MRI examinations were performed, and data were correlated with histomorphometry. PET data were analyzed using a Gjedde-Patlak plot. K-values from the plot correspond to the metabolic rate. T2-values were calculated by T2 mapping. Results: rhBMP-2 presented the highest bone formation on histologic sections at 25.6% at 4 weeks after surgery. Eight weeks after surgery, autograft had the highest bone formation with 37.3%, which was significantly higher than rhBMP-2 at 30.5% (P < 0.05), and higher than COLLOSS E at 27.0% (P = 0.06). COLLOSS E and rhBMP-2 had significantly higher K-values than autograft (P < 0.05) at 2 weeks after surgery. There were no differences in K-values between COLLOSS E and autograft at 4 and 8 weeks. However, rhBMP-2 was significantly higher at 4 weeks and lower at 8 weeks than these 2 (P < 0.05). Linear correlation, R = 0.8275, was observed for intertrabecular volume/total volume and T2-values. Conclusions: PET and MRI are valid tools for monitoring the process of interbody fusion in vivo. Osteogenic mechanisms using COLLOSS E resembles that of autograft by the process of endochondral ossification. rhBMP-2 deposits osteoid directly on the collagen network.
Publication Date: 2008-11-13 PubMed ID: 19002076DOI: 10.1097/BRS.0b013e31817fce91Google Scholar: Lookup
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  • Comparative Study
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research article presents an experimental study aimed at monitoring spinal fusion using three different substances – equine bone protein extract (COLLOSS E), recombinant human bone morphogenetic protein-2 (rhBMP-2), and autograft. The study employed imaging methods such as positron emission tomography (PET) and magnetic resonance imaging (MRI) to monitor the process. The results indicate that rhBMP-2 showed the highest bone formation 4 weeks after surgery, but autograft yielded greater bone formation after 8 weeks.

Objective and Background

  • The objective of the study was to observe the early stages of spinal fusion using three different substances, namely equine bone protein extract (COLLOSS E), recombinant human bone morphogenetic protein-2 (rhBMP-2), and autograft. The process was monitored using positron emission tomography (PET) and magnetic resonance imaging (MRI).
  • The background of the study is rooted in the fact that various growth and differentiation factors are used to induce bone formation in spinal fusion. However, the mechanisms and timeline of bone formation using these substitutes were not well-known.

Methods

  • The experiment was conducted on eighteen female Danish landrace pigs that underwent a 3-level anterior lumbar interbody fusion procedure.
  • Each group of 6 pigs was observed for variable periods – 2, 4, or 8 weeks. During the observation period, PET and MRI examinations were performed and the obtained data were compared with histomorphometry.
  • The metabolic rate was identified using K-values from a Gjedde-Patlak plot, and T2 values were calculated for T2 mapping.

Results

  • After 4 weeks, rhBMP-2 showed the highest bone formation. However, after 8 weeks, autograft had the highest bone formation, greater than both rhBMP-2 and COLLOSS E.
  • COLLOSS E and rhBMP-2 had notably higher K-values than autograft 2 weeks after surgery. There were negligible differences in K-values between COLLOSS E and autograft at 4 and 8 weeks but rhBMP-2’s K-value was higher at 4 weeks and lower at 8 weeks.
  • A strong linear correlation was observed between the intertrabecular volume/total volume and T2-values, indicating the accuracy of using these parameters for assessment.

Conclusions

  • The study concluded that PET and MRI can be effectively used to monitor the process of interbody fusion in real-time.
  • The osteogenic mechanisms using COLLOSS E were found to resemble that of autograft through the process of endochondral ossification. On the other hand, rhBMP-2 deposited osteoid directly on the collagen network.

Cite This Article

APA
Foldager C, Bendtsen M, Zou X, Zou L, Olsen AK, Munk OL, Stødkilde-Jørgensen H, Bünger C. (2008). ISSLS prize winner: positron emission tomography and magnetic resonance imaging for monitoring interbody fusion with equine bone protein extract, recombinant human bone morphogenetic protein-2, and autograft. Spine (Phila Pa 1976), 33(25), 2683-2690. https://doi.org/10.1097/BRS.0b013e31817fce91

Publication

ISSN: 1528-1159
NlmUniqueID: 7610646
Country: United States
Language: English
Volume: 33
Issue: 25
Pages: 2683-2690

Researcher Affiliations

Foldager, Casper
  • Orthopaedic Research Laboratory, Aarhus University Hospital, Aarhus, Denmark. foldager@ki.au.dk
Bendtsen, Michael
    Zou, Xuenong
      Zou, Lijin
        Olsen, Aage Kristian
          Munk, Ole Lajord
            Stødkilde-Jørgensen, Hans
              Bünger, Cody

                MeSH Terms

                • Animals
                • Awards and Prizes
                • Bone Morphogenetic Protein 2
                • Bone Morphogenetic Proteins / administration & dosage
                • Bone Substitutes / administration & dosage
                • Female
                • Horses
                • Humans
                • Magnetic Resonance Imaging / methods
                • Positron-Emission Tomography / methods
                • Prospective Studies
                • Random Allocation
                • Recombinant Proteins / administration & dosage
                • Spinal Fusion / methods
                • Sus scrofa
                • Transforming Growth Factor beta / administration & dosage
                • Transplantation, Autologous / instrumentation
                • Transplantation, Autologous / methods

                Citations

                This article has been cited 3 times.
                1. Foldager CB, Nyengaard JR, Lind M, Spector M. A Stereological Method for the Quantitative Evaluation of Cartilage Repair Tissue. Cartilage 2015 Apr;6(2):123-32.
                  doi: 10.1177/1947603514560655pubmed: 26069715google scholar: lookup
                2. 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
                3. Foldager CB, Bendtsen M, Bünger C. PET scanning for evaluation of bone metabolism. Acta Orthop 2009 Dec;80(6):737-8; author reply 738-9.
                  doi: 10.3109/17453670903487040pubmed: 19995324google scholar: lookup