Posterolateral Lumbar Spinal Fusion Research Articles

EVALUATION OF A CALCIUM PHOSPHATE-COLLAGEN MATRIX BONE GRAFT WITH NEEDLE-SHAPED SUBMICRON SURFACE TOPOGRAPHY IN A CLINICALLY RELEVANT SHEEP POSTEROLATERAL LUMBAR SPINE FUSION MODEL

Biphasic calcium phosphate (BCP) with a characteristic needle-shaped submicron surface topography (MagnetOs) has attracted much attention due to its unique bone-forming ability which is essential for repairing critical-size bone defects such as those found in the posterolateral spine. Previous in vitro and ex-vivo data performed by van Dijk LA and Yuan H demonstrated that these specific surface characteristics drive a favorable response from the innate immune system.This study aimed to evaluate and compare the in vivo performance of three commercially-available synthetic bone grafts, (1) i-FACTOR Putty®, (2) OssDsign® Catalyst Putty and (3) FIBERGRAFT® BG Matrix, with that of a novel synthetic bone graft in a clinically-relevant instrumented sheep posterolateral lumbar spine fusion (PLF) model. The novel synthetic bone graft comprised of BCP granules with a needle-shaped submicron surface topography (MagnetOs) embedded in a highly porous and fibrillar collagen matrix (MagnetOs Flex Matrix).Four synthetic bone grafts were implanted as standalone in an instrumented sheep PLF model for 12 weeks (n=3 bilateral levels per group; levels L2/3 & L4/5), after which spinal fusion was determined by manual palpation, radiograph and µCT imaging (based on the Lenke scale), range-of-motion mechanical testing, and histological and histomorphological evaluation.Radiographic fusion assessment determined bilateral robust bone bridging (Lenke scale A) in 3/3 levels for MagnetOs Flex Matrix compared to 1/3 for all other groups. For µCT, bilateral fusion (Lenke scale A) was found in 2/3 levels for MagnetOs Flex Matrix, compared to 0/3 for i-FACTOR Putty®, 1/3 for OssDsign® Catalyst Putty and 0/3 for FIBERGRAFT® BG Matrix. Fusion assessment for MagnetOs Flex Matrix was further substantiated by histology which revealed significant graft resorption complemented by abundant bone tissue and continuous bony bridging between vertebral transverse processes resulting in bilateral spinal fusion in 3/3 implants.These results show that MagnetOs Flex Matrix achieved better fusion rates compared to three commercially-available synthetic bone grafts when used as a standalone in a clinically-relevant instrumented sheep PLF model.

Effects of Preoperative Use of Povidone-Iodine–Impregnated Dressing on Postoperative Rate of Surgical Site Infection in Patients Undergoing Posterolateral Lumbar Spinal Fusion Surgery: A Randomized, Nonblinded, Active-Controlled Trial

BACKGROUND AND OBJECTIVES: No study has evaluated the efficacy of using preoperative antiseptic dressings in reducing the rate of surgical site infection (SSI) in spine surgery thus far. To investigate the efficacy of the use of preoperative povidone-iodine–impregnated antiseptic dressings in patients undergoing instrumented posterolateral lumbar spinal fusion. METHODS: This was a randomized, nonblinded, active-controlled, parallel-group clinical trial. Patients were randomly assigned to the 2 study groups, including treatment and control. Patients in the treatment group received povidone-iodine–impregnated antiseptic dressing applied to the anticipated incision site 12 hours before the operation. The control group merely received the standard perioperative care with no additional intervention or placebo. Patients were followed up for 90 days, and SSIs were recorded. RESULTS: A total of 200 patients were included in this study (100 in each arm). Three cases of SSI were observed in the treatment group compared with 12 in the control one. A significant reduction in the postoperative rate of SSI was observed in the treatment group compared with the control one (P = .029). In addition to study intervention (P = .029), body mass index (P = .005), smoking status (P = .005), duration of the procedure (P = .003), American Society of Anesthesiologists class (P = .002), and diabetes mellitus (P < .001) were significantly associated with the postoperative rate of SSI. CONCLUSION: To the best of our knowledge, this study for the first time showed that preoperative use of antiseptic dressings is significantly effective in reducing the rate of SSI in instrumented posterior lumbar spinal fusion surgery. Future studies are warranted to evaluate the efficacy of different preparations or the effectiveness of the present one in patients undergoing spine procedures with other surgical characteristics.

Effects of local intraoperative epidural use of triamcinolone acetonide-soaked Gelfoam on postoperative outcomes in patients undergoing posterolateral lumbar spinal fusion surgery: a randomized, placebo-controlled, double-blind trial.

Prior evidence has supported the use of local intraoperative epidural steroids in lumbar discectomy for improvements in postoperative pain and outcomes. However, currently there is a paucity of data regarding the efficacy of local epidural steroids in spinal fusion procedures. The present investigation aimed to evaluate the impact of local epidural administration of triamcinolone acetonide-soaked Gelfoam on postoperative pain and patient-reported outcomes in patients undergoing instrumented posterolateral lumbar spinal fusion. In this randomized, double-blind, placebo-controlled trial, patients were randomly divided into two groups (treatment and control). Patients in the treatment group received a Gelfoam carrier soaked in 1 ml of triamcinolone acetonide (40 mg), which was placed over the nerve roots in the epidural space before the closure. Patients in the control group received a Gelfoam carrier soaked in normal saline in a similar fashion to the treatment group. Patients were followed up during their hospital stay and at 4 and 12 weeks postoperatively. The primary outcome measure was early postoperative visual analog scale (VAS) scores for pain both at rest and with movement. A total of 100 patients were recruited in this study and were randomly allocated to the treatment or control group. No significant difference was found in baseline demographic, clinical, and surgical characteristics between the two groups. Postoperative VAS scores for pain both at rest and with movement were comparable between the treatment and control groups. Cumulative morphine consumption, length of hospital stay, and incidence of postoperative complications such as surgical site infection were also similar between the two groups. There was no significant difference in patient-reported outcomes including VAS scores for back and leg pain as well as the Oswestry Disability Index at 4 and 12 weeks postoperatively. The proportion of patients who achieved a minimum clinically important difference for patient-reported outcomes were also similar between the two groups. In contrast to the existing literature on the beneficial use of local intraoperative epidural steroids in conventional lumbar discectomy, the present study did not demonstrate such significant efficacy for the use of local epidural steroids in instrumented posterolateral lumbar spinal fusion. However, there is still a lack of evidence in this regard and further high-quality clinical trials are required to evaluate the efficacy of local epidural steroids in this group of patients.

Highly porous multiple-cell-laden collagen/hydroxyapatite scaffolds for bone tissue engineering

Efficient vascularization within a scaffold is an essential criterion for evaluating the success of volumetric bone formation. Various strategies using angiogenic growth factors and cell-based approaches to induce effective osteogenic and angiogenic activities have been investigated. In this study, we propose a new highly porous multiple-cell-laden collagen/hydroxyapatite scaffold fabricated using a whipped bioink. After in vitro culturing of cells in the porous scaffolds for an extended culture period, osteogenic and angiogenic activities were significantly enhanced owing to the well-developed microporous cell-supporting matrix inducing efficient crosstalk between the adipose stem cells and endothelial cells compared to those of the normally bioprinted cell-constructs. Furthermore, the in vitro results were thoroughly evaluated by in vivo experiments using a posterolateral lumbar spinal fusion model of an ovariectomized mouse. Based on these results, the porous multiple-cell-laden scaffolds enhanced spine fusion in the event of osteoporosis.

A multicellular bioprinted cell construct for vascularized bone tissue regeneration

• A bioprinting strategy using a biocompatible collagen/β-TCP bioink and the hASC/endothelial cells was proposed. • hASC/HUVEC-laden structures with cell-differentiation niches for bone regeneration were proposed. • The bioprinted structure induced significantly greater new bone and blood vessel formation. In the present study, a bioprinted cell-laden construct consisting of collagen, β-tricalcium phosphate, and two different cell types, human adipose stem cells (hASCs) and human umbilical vein endothelial cells (HUVECs), was prepared for bone tissue regeneration in spinal fusion. By using the appropriate printing parameters and bioceramic/cell compositions in the bioink, a 3D cell-laden construct consisting of microscale struts was successfully generated. To evaluate the contribution of the laden stem cells and endothelial cells in promoting angiogenic and osteogenic activities, differentiation of the cells within the bioink was analyzed by measuring gene expression profiles and immunofluorescence imaging. The hASC/HUVEC-laden structure exhibited a strong angiogenic phenotype and upregulated angiogenic factors, as well as enhanced expression of osteogenic gene markers due to the synergistic crosstalk of the two cell types. The construct laden with hASCs/HUVECs was implanted in a mouse model of posterolateral lumbar spinal fusion, and the structure provided significantly higher new bone formation and angiogenesis compared with constructs laden with only hASCs. The in vitro and in vivo findings suggest that biomimetic cell-laden constructs could perform as potential bone tissue regenerating structures to encourage effective spinal fusion.

Rates and risk factors associated with 30- and 90-day readmissions and reoperations after spinal fusions for adult lumbar degenerative pathology and spinal deformity.

Analyze state databases to determine variables associated with of short-term readmissions and reoperations following thoracolumbar spine fusions for degenerative pathology and spinal deformity. Retrospective study of State Inpatient Database (2005-13, CA, NE, NY, FL, NC, UT). age > 45years, diagnosis of degenerative spinal deformity, ≥ 3 level posterolateral lumbar spine fusion. revision surgery, cervical fusions, trauma, and cancer. Univariate and step-wise multivariate logistic regression analyses were performed to identify independent variables associated with of 30- and 90-day readmissions and reoperations. 12,641 patients were included. All-cause 30- and 90-day readmission rates were 14.6% and 21.1%, respectively. 90-day readmissions were associated with: age > 80 (OR: 1.42), 8 + level fusions (OR: 1.19), hospital length of stay (LOS) > 7days (OR: 1.43), obesity (OR: 1.29), morbid obesity (OR: 1.66), academic hospital (OR: 1.13), cancer history (OR:1.21), drug abuse (OR: 1.31), increased Charlson Comorbidity index (OR: 1.12), and depression (OR: 1.20). Private insurance (OR: 0.64) and lumbar-only fusions (OR: 0.87) were not associated with 90-day readmissions. All-cause 30- and 90-day reoperation rates were 1.8% and 4.2%, respectively. Variables associated with 90-day reoperations were 8 + level fusions (OR: 1.28), LOS > 7days (OR: 1.43), drug abuse (OR: 1.68), osteoporosis (OR: 1.26), and depression (OR: 1.23). Circumferential fusion (OR: 0.58) and lumbar-only fusions (OR: 0.68) were not associated with 90-day reoperations. 30- and 90-day readmission and reoperation rates in thoracolumbar fusions for adult degenerative pathology and spinal deformity may have been underreported in previously published smaller studies. Identification of modifiable risk factors is important for improving quality of care through preoperative optimization.

Instrumented Versus Noninstrumented Spinal Fusion for Degenerative Lumbar Spondylolisthesis: A Systematic Review.

Systematic review. This systematic review compares radiographic and clinical outcomes between instrumented and noninstrumented posterolateral lumbar spine fusions for the treatment of degenerative lumbar spondylolisthesis. The optimal method of fusion for instability from degenerative lumbar spondylolisthesis remains to be an area of debate amongst spine surgeons. There are no prior comprehensive systematic review of comparative studies that compares outcomes between instrumented and noninstrumented posterolateral spine fusions for the treatment of degenerative lumbar spondylolisthesis. A systematic review was registered with PROSPERO and performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines using the PubMed, SCOPUS, and Ovid MEDLINE databases. All level I-III comparative studies published in the English language investigating the clinical outcomes between instrumented and noninstrumented posterolateral spine fusions for the treatment of degenerative lumbar spondylolisthesis were included. Seven studies (672 patients, 274 noninstrumented, 398 instrumented) were analyzed. One randomized study was level I evidence, 2 randomized studies were level II, and 4 nonrandomized studies were level III. Mean follow-up ranged from 1.4 to 5.9 years. Instrumented patients had a higher rate of solid fusion (87.6% vs. 77.1%, P=0.023) and a lower rate of definitive pseudarthrosis (5.3% vs. 19.9%, P<0.001). However, there was no difference in overall functional improvement at final follow-up between the 2 treatment groups (75.0% vs. 81.7%, P=0.258). In addition, there was no difference in reoperation or complication rates. For the treatment of degenerative lumbar spondylolisthesis, there are significantly higher rates of fusion among patients undergoing instrumented posterolateral fusion compared with noninstrumented posterolateral fusion. However, there is no difference in overall functional improvement, pain-related outcome scores, reoperation rates, or complication rates between the 2 treatment groups. Level III-systematic review of level I-III studies.

Improved Posterolateral Lumbar Spinal Fusion Using a Biomimetic, Nanocomposite Scaffold Augmented by Autologous Platelet-Rich Plasma

Remodeling of the human bony skeleton is constantly occurring with up to 10% annual bone volume turnover from osteoclastic and osteoblastic activity. A shift toward resorption can result in osteoporosis and pathologic fractures, while a shift toward deposition is required after traumatic, or surgical injury. Spinal fusion represents one such state, requiring a substantial regenerative response to immobilize adjacent vertebrae through bony union. Autologous bone grafts were used extensively prior to the advent of advanced therapeutics incorporating exogenous growth factors and biomaterials. Besides cost constraints, these applications have demonstrated patient safety concerns. This study evaluated the regenerative ability of a nanostructured, magnesium-doped, hydroxyapatite/type I collagen scaffold (MHA/Coll) augmented by autologous platelet-rich plasma (PRP) in an orthotopic model of posterolateral lumbar spinal fusion. After bilateral decortication, rabbits received either the scaffold alone (Group 1) or scaffold with PRP (Group 2) to the anatomic right side. Bone regeneration and fusion success compared to internal control were assessed by DynaCT with 3-D reconstruction at 2, 4, and 6 weeks postoperatively followed by comparative osteogenic gene expression and representative histopathology. Both groups formed significantly more new bone volume than control, and Group 2 subjects produced significantly more trabecular and cortical bone than Group 1 subjects. Successful fusion was seen in one Group 1 animal (12.5%) and 6/8 Group 2 animals (75%). This enhanced effect by autologous PRP treatment appears to occur via astounding upregulation of key osteogenic genes. Both groups demonstrated significant gene upregulation compared to vertebral bone controls for all genes. Group 1 averaged 2.21-fold upregulation of RUNX2 gene, 3.20-fold upregulation of SPARC gene, and 3.67-fold upregulation of SPP1 gene. Depending on anatomical subgroup (cranial, mid, caudal scaffold portions), Group 2 had significantly higher average expression of all genes than both control and Group 1–RUNX2 (8.23–19.74 fold), SPARC (18.67–55.44 fold), and SPP1 (46.09–90.65 fold). Our data collectively demonstrate the osteoinductive nature of a nanostructured MHA/Coll scaffold, a beneficial effect of augmentation with autologous PRP, and an ability to achieve clinical fusion when applied together in an orthotopic model. This has implications both for future study and biomedical innovation of bone-forming therapeutics.

P1. Efficacy of a calcium phosphate collagen matrix bone graft with needle-shaped submicron surface topography in a rabbit posterolateral lumbar spine fusion model

<h3>BACKGROUND CONTEXT</h3> Synthetic bone grafts are a promising alternative for the treatment of degenerative spine conditions and are available without the added drawbacks associated autografts including limited availability and donor-site morbidity. Of these synthetic materials, calcium phosphate (CaP) with a characteristic needle-shaped submicron surface topography (BCP<µm) has attracted much attention due to its unique bone-forming ability which is essential for repairing critical-size bone defects such as those found in the posterolateral spine [1,2]. Previous in vitro and ex-vivo data presented by van Dijk LA [3] and Yuan H [4] at NASS, 2020 demonstrated that these specific surface characteristics drive a favorable response from the innate immune system. <h3>PURPOSE</h3> This study was to evaluate the efficacy of a novel synthetic bone graft using a clinically-relevant "Boden" rabbit posterolateral spine fusion model. The synthetic bone graft comprised of CaP granules with a needle-shaped submicron surface structure (BCP<µm) embedded in a highly porous and fibrillar bovine type I collagen matrix (col-BCP<µm). The fibrillar collagen was introduced as a carrier, designed to facilitate admixing of the graft with biological fluids perioperatively and to minimize graft migration postoperatively. <h3>STUDY DESIGN/SETTING</h3> The novel synthetic bone graft was first mixed in a 1:1 volume ratio with autologous bone (ABG). Subsequently, grafts were implanted in the rabbit posterolateral spine environment for 3 days, 6, 9 and 12 weeks. An autologous bone graft group was used as a positive control in this study. Outcomes for the test article were additionally compared to historical data for the same material (BCP<µm) implanted alone, without the fibrillar collagen carrier. <h3>OUTCOME MEASURES</h3> Spinal fusion was determined by manual palpation (MP), X-ray and µCT imaging (based on the Lenke scale), mechanical testing (range of motion testing at 12 weeks only) and histology (decalcified and undecalcified). <h3>METHODS</h3> Forty skeletally mature New Zealand white rabbits were divided into two groups and underwent single-level bilateral posterolateral intertransverse process spine arthrodesis at L4-5. Animals were euthanized after 3 days, 6, 9 and 12 weeks. <h3>RESULTS</h3> Based on all endpoints, the test group and positive control group showed an equivalent and gradual progression in bone formation and implant resorption over time, leading to mature fusion masses at 12 weeks. No adverse reactions were observed in any of the groups. Bilateral fusion rates by MP were consistent with the literature (0-40% at 6 weeks; 60-70% at 12 weeks) and similar trends were seen by histological and radiographic assessment (both X-ray and µCT). Flexion-extension and lateral bending results at 12 weeks demonstrated fusion of the treated level consistent with the MP results. The results observed for the test group were consistent with those seen historically for the same material implanted without the fibrillar collagen carrier. <h3>CONCLUSIONS</h3> These results show that BCP with needle-shaped submicron-scale surface topography (BCP<µm) combined with a fibrillar collagen matrix (col-BCP<µm) could achieve equivalent fusion rates to ABG when used as a bone graft extender in a clinically relevant single level rabbit intertransverse process posterolateral lumbar fusion model. Over time, a progression in bone healing, graft resorption and remodeling were seen with all experimental endpoints, with equivalency between the groups. The results for col-BCP<µm were consistent with those previously seen for BCP<µm alone, confirming that the fibrillar collagen carrier improved handling properties but was not detrimental to the bone-forming capacity of the BCP<µm. <h3>FDA DEVICE/DRUG STATUS</h3> Col-BCP<µm (Investigational/Not approved)

Bone tissue engineering via application of a collagen/hydroxyapatite 4D-printed biomimetic scaffold for spinal fusion

The fabrication of biomimetic scaffolding is a challenging issue in tissue engineering. Scaffolds must be designed with micrometer precision to enable cell proliferation and tissue growth, requiring customization based on the type of tissue being developed. Biomimetic scaffolds have attracted interest for their potential in spinal fusion applications. By providing a structured environment to promote osteogenesis, these materials offer a robust and minimally invasive means to fuse vertebrae. The present study describes the successful preparation of a biomimetic collagen/hydroxyapatite hierarchical scaffold, with each strut having several microchannels via 3D printing, leaching, and coating processes (i.e., one-way shape morphing, 4D printing). The biophysical properties of the scaffold were analyzed, as were its various cellular activities, using human adipose stem cells. This biomimetic microchannel scaffold demonstrated great potential for osteogenic activities in vitro and significantly increased new bone formation and ingrowth of blood vessels in vivo in a mouse model of posterolateral lumbar spinal fusion. These in vitro and in vivo results suggest that the microchannel collagen/hydroxyapatite scaffold could act as a potential bone graft substitute to promote high rates of successful fusion.

P122. Use of a novel allograft in single- and two-level posterolateral lumbar spinal fusion: two-year clinical and radiographic results from a prospective multicenter study

BACKGROUND CONTEXT Instrumented posterolateral lumbar fusion (PLF) surgery is commonly used to alleviate pain and other symptoms associated with degenerative conditions of the lumbosacral spine. Although autologous iliac crest bone graft (ICBG) remains the gold standard graft material for PLF, surgeons have sought alternatives to avoid morbidities associated with ICBG harvest. OSTEOAMP® is a novel allograft bone graft substitute (BGS) that retains multiple endogenous growth factors. Evidence concerning effectiveness of PLF in multi-level fusion is scarce. PURPOSE The purpose of this study was to compare 2-year clinical and radiographic outcomes of OSTEOAMP and ICBG in single- and 2-level PLF. STUDY DESIGN/SETTING This was a prospective multicenter cohort study (level 2 evidence) involving nine centers in the United States. PATIENT SAMPLE A total of 42 patients with Oswestry Disability Index (ODI) score of at least 30 at baseline were prospectively enrolled and underwent a single- (N=26) or two-level (N=16) PLF utilizing the novel BGS. 38/42 (90.5%) and 32/42 (76.2%) subjects attended 12- and 24-month follow-ups, respectively. OUTCOME MEASURES ODI, SF-36v2 PCS, SF-36v2 MCS, back and leg pain. METHODS Data was obtained preoperatively and at 1.5, 3, 6, 12, and 24 months. Radiographic studies were assessed by an independent core lab for evidence of bridging bone and lack of segmental angular ( RESULTS The two-year fusion rate for the novel BGS was 32/37 (86.5%) compared to the literature average of 76% (range 40%-100%) for ICBG. The fusion rate was 90.9% (20/22) in single- and 80% (12/15) in 2-level PLF (p=0.377). While ODI improved in both groups, the improvement was larger in single- than in 2-level subjects (p=0.058). At 24 months, the improvement in ODI was 33.5 and 25.9 in single- and 2-level subjects, respectively. There was a tendency for greater improvements at 24 months in single-level compared to 2-level PLF in SF36 PCS (15.4 vs 12.5) and SF36MCS (7.9 vs 5.6), but these differences did not reach statistical significance. Improvements in pain at back (4.8 vs 4.6) and pain at leg (4.8 vs 4.3) were similar in single- and 2-level surgeries. One secondary surgery was performed at 3 months postoperatively for a symptomatic screw in single-level subject. No product-related treatment complications were reported. CONCLUSIONS Two-level PLF is associated with poorer ODI but similar pain outcomes compared to single-level PLF. OSTEOAMP is safe and effective for use in posterolateral spinal fusion as evidenced by fusion rates higher than for ICBG, good clinical outcomes, and freedom from serious product-related complications. FDA DEVICE/DRUG STATUS OSTEOAMP® is compliant to 21 CFR 1271 and is regulated as a 361 HCT/P.

The temporal and spatial expression of sclerostin and Wnt signaling factors during the maturation of posterolateral lumbar spine fusions.

The bone healing environment in the posterolateral spine following arthrodesis surgery is one of the most challenging in all of orthopedics and our understanding of the molecular signaling pathways mediating osteogenesis during spinal fusion is limited. In this study, the spatial and temporal expression pattern of Wnt signaling factors and inhibitors during spinal fusion was assessed for the first time. Bilateral posterolateral spine arthrodesis with autologous iliac crest bone graft was performed on 21 New Zealand White rabbits. At 1‐, 2‐, 3‐, 4‐, and 6‐weeks, the expression of sclerostin and a variety of canonical and noncanonical Wnts signaling factors was measured by qRT‐PCR from tissue separately collected from the transverse processes, the Outer and Inner Zones of the fusion mass, and the adjancent paraspinal muscle. Immunohistochemistry for sclerostin protein was also performed. Sclerostin and many Wnt factors, especially Wnt3a and Wnt5a, were found to have distinct spatial and temporal expression patterns. For example, harvesting ICBG caused a significant increase in sclerostin expression. Furthermore, the paraspinal muscle immediately adjacent to the transplanted ICBG also had significant increases in sclerostin expression at 3 weeks, suggesting new potential mechanisms for pseudarthroses following spinal arthrodesis. The presented work is the first description of the spatial and temporal expression of sclerostin and Wnt signaling factors in the developing spine fusion, filling an important knowledge gap in the basic biology of spinal fusion and potentially aiding in the development of novel biologics to increase spinal fusion rates.

Comparison of Fusion Rate between Demineralized Bone Matrix versus Autograft in Lumbar Fusion : Meta-Analysis

The demineralized bone matrix (DBM) as the bone graft material to increase the fusion rate was widely used in spinal fusion. The current study aimed to compare the fusion rate of DBM to the fusion rate of autograft in lumbar spine fusion via meta-analysis of published literature. After systematic search, comparative studies were selected according to eligibility criteria. Checklist (risk of bias assessment tool for non-randomized study) was used to evaluate the risk of bias of the included nonrandomized controlled studies. The corresponding 95% confidence interval (95% CI) were calculated. We also used subgroup analysis to analyze the fusion rate of posterolateral lumbar fusion and lumbar interbody fusion. Eight studies were finally included in this meta-analysis. These eight studies included 581 patients. Among them, 337 patients underwent spinal fusion surgery using DBM (DBM group) and 204 patients underwent spinal fusion surgery with mainly autologous bone and without using DBM (control group). There was no significant differences of fusion rate between the two groups in posterolateral fusion analysis (risk ratio [RR], 1.03; 95% CI, 0.90–1.17; p=0.66) and interbody fusion analysis (RR, 1.13; 95% CI, 0.91–1.39; p=0.27). Based on the available evidence, the use of DBM with autograft in posterolateral lumbar spine fusion and lumbar interbody fusion showed a slightly higher fusion rate than that of autograft alone; however, there was no statistically different between two groups.

Posterolateral lumbar spine fusion with unidirectional porous beta-tricalcium phosphate in a canine model

We investigated the use of the autologous iliac bone and unidirectional porous beta-tricalcium phosphate (UDPTCP) in posterolateral lumbar spine fusion (PLF). Ten canine PLF models were prepared. Using only the autologous bone as the control group, 100%, 75%, 50%, and 25% groups were prepared according to the mixing ratios of UDPTCP. Radiological evaluation and histological analysis were performed 12weeks after surgery. Bone fusion was evaluated according to anteroposterior plain X-rays and coronal reconstruction CT views using four grades: 0 = no osteogenesis, 1 = only slight discontinuous osteogenesis between transverse processes, 2 = discontinuous osteogenesis between transverse processes, and 3 = continuous osteogenesis between transverse processes. Bone fusion determined by X-ray was 2.8 ± 0.5 in the control group, 0 in the 100% UDPTCP group (p = 0.02), 1.8 ± 0.5 (p = 0.03) in the 75% UDPTCP group, 2.5 ± 0.6 (p = 0.54) in the 50% UDPTCP group, and 2.8 ± 0.5 (p = 1.0) in the 25% UDPTCP group. The bone fusion score was significantly lower in the 75% and 100% UDPTCP groups than in the control group. Bone fusion determined by CT was 2.8 ± 0.5 in the control group, 1.0 ± 0.8 (p = 0.01) in the 100% UDPTCP group, 2.0 ± 0.0 (p = 0.02) in the 75% UDPTCP group, 2.5 ± 0.6 (p = 0.54) in the 50% UDPTCP group, and 2.8 ± 0.5 (p = 1.0) in the 25% UDPTCP group. Similar to the bone fusion determination by X-ray, the bone fusion score was significantly lower in the 75% and 100% UDPTCP groups. These data suggest that, in a canine PLF model, the appropriate mixing ratio of UDPTCP is 50% or less.

Autologous blood coagulum is a physiological carrier for BMP6 to induce new bone formation and promote posterolateral lumbar spine fusion in rabbits.

In the present study, we describe autologous blood coagulum (ABC) as a physiological carrier for BMP6 to induce new bone formation. Recombinant human BMP6 (rhBMP6), dispersed within ABC and formed as an autologous bone graft substitute (ABGS), was evaluated either with or without allograft bone particles (ALLO) in rat subcutaneous implants and in a posterolateral lumbar fusion (PLF) model in rabbits. ABGS induced endochondral bone differentiation in rat subcutaneous implants. Coating ALLO by ABC significantly decreased the formation of multinucleated foreign body giant cells (FBGCs) in implants, as compared with ALLO alone. However, addition of rhBMP6 to ABC/ALLO induced a robust endochondral bone formation with little or no FBGCs in the implant. In rabbit PLF model, ABGS induced new bone formation uniformly within the implant resulting in a complete fusion when placed between two lumbar transverse processes in the posterolateral gutter with an optimum dose of 100‐μg rhBMP6 per ml of ABC. ABGS containing ALLO also resulted in a fusion where the ALLO was replaced by the newly formed bone via creeping substitution. Our findings demonstrate for the first time that rhBMP6, with ABC as a carrier, induced a robust bone formation with a complete spinal fusion in a rabbit PLF model. RhBMP6 was effective at low doses with ABC serving as a physiological substratum providing a permissive environment by protecting against foreign body reaction elicited by ALLO.

167. Assessment of the efficacy of teriparatide (Forteo) in patients undergoing posterolateral lumbar spinal fusion: a double-blinded randomized pilot study

BACKGROUND CONTEXT Lumbar spinal fusion is an increasingly common procedure for treating degenerative diseases of the lumbar spine. Non-solid fusion, or pseudarthrosis, at one year is a common complication associated with poor clinical outcomes and need for revision surgery. The risk of pseudarthrosis depends on the number of levels fused, the fusion material, and patient risk factors (osteoporosis, smoking, diabetes, etc.). Although there are multiple options for bone graft and osteoinductive materials, all have their benefits, side-effects and cost. Teriparatide is an injectable recombinant analog of parathyroid hormone that has been well-studied in its treatment of osteoporosis. However, no clinical studies of its effect on spinal fusion in humans have been published to date. PURPOSE To analyze the effect of teriparatide treatment on posterolateral spinal fusion in adults with degenerative diseases of the lumbar spine. STUDY DESIGN/SETTING Multicenter prospective double-blinded randomized study. PATIENT SAMPLE 60-90 year-olds with degenerative scoliosis, spondylolisthesis, or spondylosis at two medical centers undergoing instrumented posterolateral instrumented fusion >2levels. Use of BMP was excluded. OUTCOME MEASURES Pseudoarthrosis, screw loosening, PJK by CT. VAS, ODI, and Eq5D. METHODS Prospective randomized double-blind placebo-controlled pilot study performed at two large academic centers, UCSF and McGill University (Montreal). Included patients were aged 60-90 years with degenerative lumbar disease who were scheduled to undergo two-level or greater posterolateral lumbar spinal fusion. Patients were randomized in a 2:1 (Forteo:Placebo) manner. Patient were dosed 2 weeks pre-op and 10 weeks post-op. Patient derived outcomes were collected pre-op, 3, 6, 9, and 12 months. Fusions at 1 year were analyzed by helical CT. RESULTS A total of 36 patients completed the study. 58.3% (n=21) received teriparatide. 42.8% (n=9) reported an adverse event. Fusion rate of all patients was 47.2% (n=17); the remaining 52.8% (n=19) demonstrated pseudoarthrosis at 1 year. Fourty-seven percent of patients receiving teriparatide had a pseudoarthrosis, while 60% of placebo had a pseudoarthrosis. VAS, ODI, and Eq5D improved in all groups but no significant difference was found between groups. CONCLUSIONS Teriparatide appears to provide minimal benefit of avoiding pseudoarthroses in 60-90 year-olds undergoing thoracolumbar fusions. Teriparatide appears to have a fairly safe side effect profile. Further larger scale studies are warranted, possibly with the addition of BMP and/or bisphosphonates. FDA DEVICE/DRUG STATUS Unavailable from authors at time of publication.

P4. Autologous blood coagulum as a native carrier for rhBMP6 induces new bone formation and posterolateral lumbar spine fusion in rabbits and sheep

BACKGROUND CONTEXT RhBMP2 soaked in bovine tendon collagen and synthetic ceramics composite as well as rhBMP7/OP1 lyophilized in bovine bone collagen particles with additive carboxyl-methyl cellulose have been evaluated for posterolateral lumbar fusion (PLF). We investigated rhBMP6 delivered in autologous blood coagulum (ABC), a native carrier (scaffold), with and without allograft bone particles (ALLO) to induce new bone formation and promote posterolateral lumbar spine fusion (PLF) in rabbit and sheep. PURPOSE To evaluate the efficacy of RhBMP6 with autologous blood coagulum (ABC) alone or with ABC and allograft (ALLO) will induce a successful posterolateral spinal fusion in animal models. STUDY DESIGN/SETTING Preclinical evaluation of spine fusion in animal models. PATIENT SAMPLE Multiple experimental groups of rats, rabbits and sheep. OUTCOME MEASURES Radiographic and histologic evaluation for bone formation and spinal fusion. METHODS An autologous bone graft substitute (ABGS) was fabricated by dispersing rhBMP6 in ABC with and without ALLO and evaluated for bone induction in rat subcutaneous implants and to promote bone formation in posterolateral lumbar fusion in preclinical models. The cellular response of bone induction and the quantity and quality of newly formed bone were examined by histology, radiographs, micro-CT analyses at various time intervals. RESULTS ABGS with and without ALLO induced new bone formation in rat implants. ALLO alone induced formation of multinucleated foreign body giant cells (FBGCs). However, ALLO plus ABC decreased the formation of FBGCs. The addition of rhBMP6 to ABC/ALLO, resulted in fewer or no FBGCs. In Rabbits, the groups with ABC alone or with ALLO did not fuse. The 50 micrograms rhBMP6 group only 2 out of 4 animals successfully fused. In the 100 micrograms, 200 micrograms and 400 micrograms rhBMP6 groups all animals successfully fused. In sheep, the groups with ABC or ABC with ALLO failed to fuse. In the rhBMP6 187.5 micro grams/ml group with ABC and instrumentation fusion was achieved in 83% (10/12 animals). In the 187.5 micro grams/ml group with ABC, ALLO and instrumentation, fusion was achieved in 93% (11/12 animals). Bone formation occurred uniformly within ABGS implants where the ALLO was replaced by the newly formed bone via creeping substitution. CONCLUSIONS RhBMP6 with autologous blood coagulum (ABC) alone or with ABC and allograft (ALLO) induced a robust bone formation in posterolateral spinal fusion in preclinical models. FDA DEVICE/DRUG STATUS RhBMP6 (Not approved for this indication).

P13. Effect of intraoperative steroid treatment on spinal fusion capacity in rat spinal arthrodesis model

BACKGROUND CONTEXT Local steroid administration during cervical spine surgery has been shown to improve postoperative dysphagia. Due to concerns for complications like pseudarthrosis, however, widespread acceptance of intraoperative local steroid administration has not been adopted for such procedures. Previous literature in a rabbit posterolateral lumbar fusion (PLF) model demonstrated inhibition of graft incorporation and consequent pseudarthrosis following postoperative intramuscular dexamethasone administration. Nevertheless, the potential complications of intraoperative local steroid administration on bone healing and spine fusion have yet to be directly investigated. PURPOSE This study aims to evaluate the effect of intraoperative local steroid administration on spinal fusion capacity in a rat model. STUDY DESIGN/SETTING Preclinical. PATIENT SAMPLE Female Sprague-Dawley rats, ages 12-16 weeks. OUTCOME MEASURES The outcome measures for this pre-clinical study are radiography, manual palpation fusion scoring, microCT and histological sectioning. METHODS Forty-five female Sprague-Dawley rats underwent bilateral posterolateral lumbar spinal fusion at L4-L5 using 0.5 mg recombinant human BMP-2 (rhBMP-2) delivered on an absorbable collagen sponge (INFUSE™; 1 mg rhBMP-2 per animal). Either no steroid (vehicle control), 0.5mg triamcinolone (low-dose steroid), or 2.5mg triamcinolone (high-dose) was added directly to the implant. (The sub-therapeutic 1 mg dose of rhBMP-2 per animal was chosen in order to avoid saturation of the fusion response and capture any potential inhibitory effect that might exist. Rats were radiographed alive at four weeks, and after euthanasia at eight weeks post-operative. Spines were then harvested and underwent manual palpation-based fusion scoring, microCT imaging, and histological sectioning. Fusion scoring was performed by three blinded observers using an established scoring system whereby 0 = no bridging bone, 1 = unilateral bridging bone, and 2 = bilateral bridging bone, with an average score of >1 considered fused. Mean fusion scores were compared using one-way ANOVA. Fusion rates were compared using Fischer's exact test. RESULTS The mean fusion scores of the control, low-dose steroid, and high-dose steroid groups were 0.61 (SD=0.59), 1.09 (SD=0.81), and 0.58 (SD=0.58), respectively. Fusion rates of the three groups were 38%, 57%, and 33%, respectively. At p>0.05, neither fusion scores nor rates were significantly different among groups (Figure 1). Data processing from MicroCT images to quantify the volume of new bone growth in fusion masses is in progress, as is histological analysis of fusion beds. CONCLUSIONS The results demonstrate that steroid delivered intraoperatively within the INFUSE™ implant during spinal fusion surgery had no adverse impact on fusion capacity in the clinically relevant rat model. Considering that intraoperative steroid use during human cervical spine surgery has been shown to minimize dysphagia, these results open the door for higher-order investigations into the potential for similar steroid use in human spine surgery patients. FDA DEVICE/DRUG STATUS Unavailable from authors at time of publication.

110. Use of a novel allograft in single-level posterolateral lumbar spine fusion surgery: 1-year clinical and radiographic results from a prospective multicenter study with comparison to reported results for ICBG

BACKGROUND CONTEXT Instrumented posterolateral lumbar fusion (PLF) surgery is commonly used to alleviate pain and other symptoms associated with degenerative conditions of the lumbosacral spine. Although autologous iliac crest bone graft (ICBG) remains the “gold standard” grafting material for these procedures, surgeons have sought alternatives to avoid the potential morbidity associated with ICBG harvest. OSTEOAMP is a novel allograft bone graft substitute (BGS) that has been processed to retain multiple endogenous growth factors. A prospective multicenter study was designed to enable comparison of this novel product to available data for autologous bone graft controls from large randomized controlled trials (RCTs). PURPOSE Compare 1-year outcomes from an ongoing study investigating radiographic and clinical outcomes to reported results for ICBG controls from a large RCT. STUDY DESIGN/SETTING Prospective multicenter single-arm study conducted in the United States. PATIENT SAMPLE Consenting patients, 21 to 85 years of age, scheduled for PLF surgery with a diagnosis of degenerative disc disease (DDD), degenerative spondylolisthesis, and/or mild degenerative scoliosis. OUTCOME MEASURES Bilateral radiographic fusion (blinded, multireader with adjudication) was assessed. Additional outcome measures included Oswestry Disability Index (ODI), Short Form-36 (SF-36) physical component summary (PCS) and mental component summary (MCS) scores, and improvement in leg/back pain scores. Product-related serious adverse events (SAEs) and secondary surgeries were also assessed. METHODS Forty-two patients were prospectively enrolled after obtaining IRB approval at each of 9 centers and underwent a 1-level (26 patients) or 2-level (16 patients) PLF procedure utilizing the novel BGS (67% BGS: 33% local bone graft). Clinical outcomes were measured and radiographic studies were obtained preop and postop at 1.5, 3, 6, and 12 months. Radiographic analysis included CT assessment of fusion at 12 months. One-year outcomes were available for 23 of the 26 patients who underwent a 1-level procedure and were compared to 1-year outcomes reported for ICBG controls from a large previously published RCT by estimation of novel BGS:ICBG Risk Ratios (RR) with 95% confidence intervals (CI). RESULTS One-year fusion rates and results for each of the measures (novel BGS vs ICBG) are as follows: bilateral fusion = 73.9% (17/23) vs 82.5% (151/183) with RR 0.90 (0.69, 1.15 CI); ODI (>15 improvement) = 73.9% (17/23) vs 73.9% (150/203), RR 1.00 (0.77, 1.29 CI); leg pain = 95.7% (22/23) vs 87.6% (177/202), RR 1.09 (0.99, 1.21 CI); back pain = 91.3% (21/23) vs 93.1% (180/203), RR 0.98 (0.86, 1.12 CI); SF-36 MCS = 73.9% (17/23) vs 68.7% (138/201), RR 1.08 (0.83, 1.40); SF-36 PCS = 95.7% (22/23) vs 86.6% (174/201), RR 1.10 (1.00, 1.22 CI). No statistically significant difference was found in RR between groups for all comparisons. No product-related SAEs and only one secondary surgery were observed with the novel BGS. CONCLUSIONS One-year clinical and radiographic outcomes following single-level PLF procedures with OSTEOAMP compare favorably to results reported for an ICBG control group from a large RCT. FDA DEVICE/DRUG STATUS OSTEOAMP (Approved for this indication)

The Effect of Proton Pump Inhibitors on Bone Formation in a Rat Spinal Arthrodesis Model.

Rat posterolateral arthrodesis model. Quantify the impact of administration of a proton pump inhibitor on spine fusion. Proton pump inhibitors (PPIs) are widely used for gastrointestinal disorders and for ulcer prophylaxis in patients taking non-steroidal anti-inflammatory drugs. PPIs cause chronic acid suppression which has been found to result in decreased bone mineral density, increased fracture risk, and impaired fracture healing. Despite advances in surgical techniques, pseudarthrosis still occurs in up to 24% of patients requiring revision surgery following spinal fusion procedures. Thus, there are likely many unidentified risk factors. While PPIs have been hypothesized to impact fracture healing, no study has evaluated their effect on spine arthrodesis rates. Thirty-eight female rats underwent posterolateral lumbar spinal fusion. Rats were divided into two groups: normal saline control and pantroprazole, which was administered by daily intraperitoneal injections. At 8 weeks postoperative spines were evaluated with manual palpation, microCT, histologic analysis, and biomechanical testing. Fusion rates of the control group and PPI group were not significantly different (100% vs. 94%). Average fusion scores were significantly lower in the pantoprazole group. New bone formation identified on microCT imaging of bilaterally fused specimens demonstrated a lower average volume of newly generated bone in the PPI group, but this difference was not significant. Biomechanical testing demonstrated no significant difference in strength or stiffness of the fusion mass between the groups. This study demonstrates that administration of PPIs does not inhibit fusion rates, bone formation, or affect biomechanical integrity of fusion. However, lower fusion scores in the PPI group suggest that a negative impact may still exist. Future studies will explore growth factor and protein expression in the fusion masses as well as utilize higher doses of PPI to fully discern their effect on spine fusion. N/A.