Posterolateral inter-transverse lumbar fusion in a mouse model.
BACKGROUND
Spinal fusion is a common orthopaedic procedure that has been previously modeled using canine, lapine, and rodent subjects. Despite the increasing availability of genetically modified mouse strains, murine models have only been infrequently described.


OBJECTIVE
To present an efficient and minimally traumatic procedure for achieving spinal fusion in a mouse model and determine the optimal rhBMP-2 dose to achieve sufficient fusion mass.


METHODS
MicroCT reconstructions of the unfused mouse spine and human spine were compared to design a surgical approach. In phase 1, posterolateral lumbar spine fusion in the mouse was evaluated using 18 animals allocated to three experimental groups. Group 1 received decortication only (n=3), Group 2 received 10 μg rhBMP-2 in a collagen sponge bilaterally (n=6), and Group 3 received 10 μg rhBMP-2 + decortication (n=9). The surgical technique was assessed for intra-operative safety, efficacy, access and reproducibility. Spines were harvested for analysis at 3 weeks (Groups 1, 2) and 1, 2, and 3 weeks (Group 3). In phase 2, a dose response study was carried out in an additional 18 animals with C57BL6 mice receiving sponges containing 0, 0.5, 1, 2.5, 5 μg of rhBMP-2 per sponge bilaterally.


RESULTS
The operative procedure via midline access was rapid and reproducible, and fusion of the murine articular processes was found to be analogous to the human procedure. Unlike reports from other species, decortication alone (Group 1) yielded no new bone formation. Addition of rhBMP-2 (Groups 2 and 3) yielded a significant bone mass that bridged the L4-L6 vertebrae. The subsequent dose response experiment revealed that 0.5 μg rhBMP-2 per sponge was sufficient to create a fusion mass.


CONCLUSIONS
We describe a new approach for mouse lumbar spine fusion that is safe, efficient, and highly reproducible. The technique we employed is analogous to the human midline procedure and may be highly suitable for genetically modified mouse models.
Orthopaedic Research & Biotechnology Unit, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, 2145, Australia.
Justin
J
Bobyn
Anton
A
Rasch
David G
DG
Little
Aaron
A
Schindeler
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007432:Intraoperative Period; D008159:Lumbar Vertebrae / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000502:physiology / Q000601:surgery*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010012:Osteogenesis / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013045:Species Specificity; D013123:Spinal Fusion / Q000009:adverse effects / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D055114:X-Ray Microtomography / Q000379:methods
D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2