Radiographic, biomechanical, and histological evaluation of rhBMP-2 in a 3-level intertransverse process spine fusion: an ovine study
Authors: Toth Jeffrey M. , Wang Mei , Lawson Joshua , Badura Jeffrey M. , DuBose Kimberly Bailey 
Published: July 2016

OBJECTIVE
The objective of this study was to evaluate bone grafts consisting of rhBMP-2 on an absorbable collagen sponge with a ceramic composite bulking agent, rhBMP-2, directly on a ceramic-collagen sponge carrier or iliac crest bone graft (ICBG) in combination with local bone graft to effect fusion in a multisegmental instrumented ovine lumbar intertransverse process fusion model.

METHODS
Thirty-six sheep had a single treatment at 3 spinal levels in both the right and left intertransverse process spaces. Group 1 sheep were treated with 7.5 cm3 of autograft consisting of ICBG plus local bone for each intertransverse process space. For Groups 2–4, 4 cm3 of local bone was placed within the intertransverse process space followed by 4.5–5 cm3 of the rhBMP-2 graft material. Group 2 animals received 1.5 mg/cm3 rhBMP-2 on an absorbable collagen sponge with a commercial bone void filler consisting of Type I lyophilized collagen with a biphasic hydroxyapatite/β-tricalcium phosphate ceramic with local bone. Group 3 animals received 0.75 mg/m cm3 of rhBMP-2 on a collagen ceramic sponge carrier with local bone. Group 4 animals received 1.35 mg/cm3 of rhBMP-2 on the same collagen ceramic sponge carrier with local bone. Sheep were euthanized 6 months postoperatively. Manual palpation, biomechanical testing, CT, radiography, and undecalcified histology were performed to assess the presence of fusion associated with the treatments.

RESULTS
All animals in Groups 2–4 that received grafts containing rhBMP-2 achieved radiographic and CT fusion at all 3 levels. In Group 1 (bone autograft alone), only 19% of the levels demonstrated radiographic fusion, 14% resulted in possible radiographic fusion, and 67% of the levels demonstrated radiographic nonfusion. Biomechanical testing showed that Groups 2–4 demonstrated similar stiffness of the L2–5 segment in all 6 loading directions, with each of the 3 groups having significantly greater stiffness than the autograft-only group. In Group 1, only 2 of 18 levels were rated as achieving bilateral histological fusion, with an additional 3 levels showing a unilateral fusion. The majority of the treated levels (13/18) in Group 1 were scored as histological nonfusions. There were no histological nonfusions in Groups 2 through 4. All 18 levels in Group 2 were rated as bilateral histological fusions. A majority (34/36) of the levels in Group 3 were rated as bilateral histological fusions, with 2 levels showing a unilateral fusion. A majority (35/36) of the levels in Group 4 were rated as bilateral histological fusions, with 1 level showing a unilateral fusion.

CONCLUSIONS
In the ovine multilevel instrumented intertransverse process fusion model, rhBMP-2 was able to consistently achieve CT, radiographic, biomechanical, and histological fusion. Compared with ICBG, the gold standard for bone grafting, rhBMP-2 was statistically superior at achieving radiographic and histological fusion.