Bone substitutes and expanders in Spine Surgery: A review of their fusion efficacies.

STUDY DESIGN: A narrative review of literature. OBJECTIVE: This manuscript intends to provide a review of clinically relevant bone substitutes and bone expanders for spinal surgery in terms of efficacy and associated clinical outcomes, as reported in contemporary spine literature. SUMMARY OF BACKGROUND DATA: Ever since the introduction of allograft as a substitute for autologous bone in spinal surgery, a sea of literature has surfaced, evaluating both established and newly emerging fusion alternatives. An understanding of the available fusion options and an organized evidence-based approach to their use in spine surgery is essential for achieving optimal results. METHODS: A Medline search of English language literature published through March 2016 discussing bone graft substitutes and fusion extenders was performed. All clinical studies reporting radiological and/or patient outcomes following the use of bone substitutes were reviewed under the broad categories of Allografts, Demineralized Bone Matrices (DBM), Ceramics, Bone Morphogenic proteins (BMPs), Autologous growth factors (AGFs), Stem cell products and Synthetic Peptides. These were further grouped depending on their application in lumbar and cervical spine surgeries, deformity correction or other miscellaneous procedures viz. trauma, infection or tumors; wherever data was forthcoming. Studies in animal populations and experimental in vitro studies were excluded. Primary endpoints were radiological fusion rates and successful clinical outcomes. RESULTS: A total of 181 clinical studies were found suitable to be included in the review. More than a third of the published articles (62 studies, 34.25%) focused on BMP. Ceramics (40 studies) and Allografts (39 studies) were the other two highly published groups of bone substitutes. Highest radiographic fusion rates were observed with BMPs, followed by allograft and DBM. There were no significant differences in the reported clinical outcomes across all classes of bone substitutes. CONCLUSIONS: There is a clear publication bias in the literature, mostly favoring BMP. Based on the available data, BMP is however associated with the highest radiographic fusion rate. Allograft is also very well corroborated in the literature. The use of DBM as a bone expander to augment autograft is supported, especially in the lumbar spine. Ceramics are also utilized as bone graft extenders and results are generally supportive, although limited. The use of autologous growth factors is not substantiated at this time. Cell matrix or stem cell-based products and the synthetic peptides have inadequate data. More comparative studies are needed to evaluate the efficacy of bone graft substitutes overall.

Repair of sheep long bone cortical defects filled with COLLOSS, COLLOSS E, OSSAPLAST, and fresh iliac crest autograft.

COLLOSS and COLLOSS E are osteoinductive bone void fillers consisting of bone collagen and noncollagenous proteins from bovine and equine bone, respectively. The aim of this study was to compare COLLOSS, COLLOSS E, iliac bone autograft, sintered beta tricalcium phosphate (beta-TCP; OSSAPLAST), and COLLOSS E plus OSSAPLAST. Materials were placed for 4, 8, or 24 weeks in 5-mm cortical bone defects in sheep long bones. Histological sections in a plane perpendicular to the long axis of the bone were used to measure the total repair area (original defect plus callus) and the area of bone within the total repair area. The incidence of defect union was also evaluated. At 4 and 8 weeks, defects treated with COLLOSS and COLLOSS E with or without OSSAPLAST had total repair and bone areas equivalent to autograft, and larger than OSSAPLAST-treated defects. At 8 weeks, the incidence of defect union was higher in defects treated with autograft or COLLOSS E plus OSSAPLAST than in untreated defects. At 24 weeks, the incidence of union was 100% in all treatment groups and 0% in untreated defects. The incidence of union was related to the degree of remodeling between 8 and 24 weeks. This was greater in all treated than nontreated defects. In conclusion, COLLOSS and COLLOSS E were equivalent to each other and to autograft, and superior to beta-TCP, in this study model.

Purified bovine BMP extract and collagen for spine arthrodesis: preclinical safety and efficacy.

STUDY DESIGN: Rabbit and nonhuman primate posterolateral intertransverse process spinal fusions were performed. OBJECTIVES: To determine the preclinical safety and efficacy of bBMPx product (a composite of collagen and bovine bone morphogenetic protein extract) mixed with demineralized bone matrix for posterolateral intertransverse process spinal fusions. SUMMARY OF BACKGROUND DATA: A dose response of bovine BMP extract with collagen in demineralized bone matrix has demonstrated spinal fusion to a rate of 100% in a rabbit spinal fusion model. This study furthers the research to demonstrate safety in the rabbit and efficacy of bovine BMP extract for spinal fusion applications in nonhuman primates. Additionally, preliminary human clinical data are presented. METHODS: For the safety portion of the study, 45 New Zealand white rabbits underwent posterolateral intertransverse process spinal fusion after laminectomy. Nine additional rabbits served as nontreated control subjects. Graft material (autograft or bBMPx product) was placed in the gutters in 30 animals, and no material was used in 15 animals. The animals were observed for abnormal physical activity, then killed at 8, 29, or 57 days. Histologic evaluation was performed on explanted spines. In the nonhuman primate efficacy studies, 54 rhesus macaques also underwent bilateral posterolateral intertransverse process fusion. bBMPx product with varying bovine BMP extract doses was implanted bilaterally. The animals were killed at 4, 8, 12, 18, or 24 weeks. Plain radiograph, computed tomography scanning, and histology were performed. RESULTS: The rabbit safety study demonstrated that any spinal cord compression or degeneration was caused by the inflammatory response after surgery and was equivalent in all groups. These issues resolved over time. Efficacy data demonstrated an autograft fusion rate of only 21% in the rhesus macaques. The bovine BMP extract demonstrated a dose response in which 3 mg per side gave twice the fusion rate as autograft. CONCLUSIONS: bBMPx product is safe and effective as an autograft substitute for posterolateral intertransverse process spinal fusion. Clinical studies are underway.