title: Radiographic, biomechanical, and histological evaluation of rhBMP-2 in a 3-level intertransverse process spine fusion: an ovine study.
abstract: 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 cm3of autograft consisting of ICBG plus local bone for each intertransverse process space. For Groups 2-4, 4 cm3of local bone was placed within the intertransverse process space followed by 4.5-5 cm3of the rhBMP-2 graft material. Group 2 animals received 1.5 mg/cm3rhBMP-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 cm3of rhBMP-2 on a collagen ceramic sponge carrier with local bone. Group 4 animals received 1.35 mg/cm3of 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.
authors.affiliation: Department of Orthopaedic Surgery, The Medical College of Wisconsin Inc., Milwaukee, Wisconsin; and.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Toth
authors.affiliation: Department of Orthopaedic Surgery, The Medical College of Wisconsin Inc., Milwaukee, Wisconsin; and.
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, The Medical College of Wisconsin Inc., Milwaukee, Wisconsin; and.
authors.forename: Joshua
authors.initials: J
authors.lastname: Lawson
authors.affiliation: Medtronic Spinal and Biologics, Memphis, Tennessee.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Badura
authors.affiliation: Medtronic Spinal and Biologics, Memphis, Tennessee.
authors.forename: Kimberly Bailey
authors.initials: KB
authors.lastname: DuBose
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D016025:Bone Transplantation / Q000295:instrumentation / Q000379:methods*; D002516:Ceramics; D003094:Collagen; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D008852:Microradiography; D010012:Osteogenesis / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage; D012756:Sheep; D013123:Spinal Fusion / Q000295:instrumentation / Q000379:methods*; D015503:Surgical Sponges; D014057:Tomography, X-Ray Computed; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*; D014182:Transplantation, Autologous / Q000295:instrumentation / Q000379:methods*
chemical_list: D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D003094:Collagen
keywords: ACS = absorbable collagen sponge; CCS = collagen ceramic sponge; HA = hydroxyapatite; ICBG = iliac crest bone graft; OLR = ordinal logistic regression; PA = posteroanterior; TCP-HA = tricalcium phosphate; autograft; lumbar fusion; multilevel spine fusion; rhBMP-2; rhBMP-2 = recombinant human bone morphogenetic protein–2