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.
METHODS
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.
Foldager
Casper
C
Orthopaedic Research Laboratory, Aarhus University Hospital, Aarhus, Denmark. foldager@ki.au.dk
Bendtsen
Michael
M
Zou
Xuenong
X
Zou
Lijin
L
Olsen
Aage Kristian
AK
Munk
Ole Lajord
OL
Stødkilde-Jørgensen
Hans
H
Bünger
Cody
C
D000818:Animals; D001363:Awards and Prizes; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage*; D018786:Bone Substitutes / Q000008:administration & dosage*; D005260:Female; D006736:Horses; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D049268:Positron-Emission Tomography / Q000379:methods*; D011446:Prospective Studies; D011897:Random Allocation; D011994:Recombinant Proteins / Q000008:administration & dosage*; D013123:Spinal Fusion / Q000379:methods*; D034421:Sus scrofa; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*; D014182:Transplantation, Autologous / Q000295:instrumentation* / Q000379:methods*
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2