Histologic Evaluation of the Efficacy of RhBMP-2 Compared with Autograft Bone in Sheep Spinal Anterior Interbody Fusion

Study Design: The sheep anterior lumbar spinal fusion model was used to study the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2)-collagen composite in comparison with autograft to enhance spinal interbody fusion. Comparisons were drawn from temporal radiographic and end-point biomechanical and histologic data.

Objective: To analyze histologically the ability of rhBMP-2 to achieve complete arthrodesis between vertebral bodies.

Summary Of Background Data: Studies using rhBMP for enhancement of anterior interbody fusion have used numerous endpoints. However, systematic histologic evaluation of the fusion has not been conducted.

Methods: Twelve sheep underwent single-level anterior lumbar interbody fusion performed with a cylindrical fenestrated titanium interbody fusion device (INTER FIX, Medtronic Sofamor Danek, Inc., Memphis, TN). The device was filled either with rhBMP-2-collagen (n = 6) or autogenous iliac crest bone graft (n = 6). Radiologic evaluation was carried out at 2-month intervals, and all sheep were killed 6 months after surgery. Nondestructive biomechanical testing for stiffness to flexion, extension, and lateral bending moments, un-decalcified histology, and qualitative and quantitative histologic evaluation were performed.

Results: Radiographs revealed a bony bridge anterior to the cage in five of six rhBMP-2-treated animals, whereas it was present only in one of five in the autogenous bone graft group. Segments treated with rhBMP-2 were 20% stiffer in flexion than autograft-treated segments at 6 months. Six of six in the rhBMP-2 group and two of six in the autograft group showed complete fusion. There was a significantly higher rate of bony continuity observed at the fenestrations of the rhBMP-2 group. Three times more number of cage fenestrations in the rhBMP-2 group demonstrated "all-bone" when compared with the autograft group (P < 0.001). Further, the scar tissue in and around the autograft-treated cages was 16-fold more (P < 0.01) than that seen for rhBMP-2-treated cages.

Conclusions: The study demonstrates that rhBMP-2 can lead to earlier radiologic fusion and a more consistent increased stiffness of the segments when compared with autograft in sheep anterior lumbar interbody fusion. Furthermore, a three times higher histologic fusion rate is attainable with significantly reduced fibrous tissue around the implant when rhBMP-2 is used.