Differences in early osteogenesis and bone micro-architecture in anterior lumbar interbody fusion with rhBMP-2, equine bone protein extract, and autograft.
OBJECTIVE
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.
Foldager
Casper
C
Orthopaedic Research Laboratory, Aarhus University Hospital, Noerrebrogade 44, building 1A, 8000 Aarhus C, Denmark. foldager@ki.au.dk
Bendtsen
Michael
M
Nygaard
Jens Vinge
JV
Zou
Xuenong
X
Bünger
Cody
C
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D003094:Collagen / Q000494:pharmacology*; D020342:Finite Element Analysis; D006736:Horses; D008159:Lumbar Vertebrae / Q000033:anatomy & histology* / Q000000981:diagnostic imaging / Q000187:drug effects*; D008954:Models, Biological; D009929:Organ Size / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology*; D013123:Spinal Fusion; D034421:Sus scrofa; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014182:Transplantation, Autologous; D055114:X-Ray Microtomography
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; C515502:COLLOSS E; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D003094:Collagen