Osseointegration of autograft versus osteogenic protein-1 in posterolateral spinal arthrodesis: emphasis on the comparative mechanisms of bone induction.

BACKGROUND CONTEXT: Recent studies have documented increased fusion success afforded by bone morphogenetic proteins versus autogenous graft for posterolateral spinal arthrodesis. PURPOSE: The current study was designed to investigate the time-course maturation processes of lumbar posterolateral arthrodeses performed with Osteogenic Protein-1 (Stryker Biotech, Inc., Hopkinton, MA, USA) (rhOP-1) versus "gold standard" autograft. STUDY DESIGN: The primary focus of this study was to compare the histologic mechanisms of posterolateral osseointegration produced by "hot topic" growth factors. METHODS: A total of 36 coonhounds were equally divided into one of four postoperative time periods of 4, 8, 12 and 24 weeks (nine animals per period). Posterolateral arthrodesis treatments included 1) autograft alone, 2) autograft plus rhOP-1, or 3) rhOP-1 alone. The treatments and animals were divided such that a value of n=6 was obtained for each treatment group per time period and no one animal received the same treatment at both operative sites. Functional spinal unit (FSU) fusion status was assessed using radiographic analysis, biomechanical testing and undecalcified histopathologic and histomorphometric analyses. RESULTS: Radiographic differences in fusion maturation between the treatment groups were evident as early as the 4-week time interval and continued through the 24-week time period. The Osteogenic Protein-1 treatments demonstrated an accelerated rate of radiographic fusion by 4 weeks, which plateaued after the 8-week time period (22% autograft, 88% autograft/rhOP-1 and 66% rhOP-1). In contradistinction, the so-called "gold standard" autograft alone treatments reached a maximum of 50% fusion by the 6-month interval. Biomechanical testing of the FSUs indicated lower flexion-extension and axial rotation range of motion levels for both rhOP-1 treatments versus autograft alone at the 8- and 12-week time periods, respectively (p<.05). Histomorphometric analysis yielded no difference in the posterolateral trabecular bone area (mm(2)) between the three treatments (p>.05), and histopathology indicated no significant histopathologic changes. The most distinctive finding in this study deals with the mechanisms of posterolateral ossification. Based on plain and polarized light microscopy, bone induction and development for the rhOP-1 treatments, with and without autograft, was the result of intramembranous ossification, whereas the process of osseointegration for autograft alone was endochondral bone formation. By the 24-week interval, no discernable differences in trabecular histomorphology were evident based on the different mechanisms of ossification. CONCLUSIONS: This serves as the first study to document the mechanisms of bone induction and fusion maturation between posterolateral arthrodeses treated with autograft versus rhOP-1. The histological data served to corroborate the radiographic and biomechanical findings, because the rhOP-1 treatments consistently demonstrated increased fusion rates and lower range of motion levels compared with the autograft group, particularly at the 8-week postoperative time period. The improvements in these fusion criteria for Osteogenic Protein-1 versus autograft were considered secondary to the differing mechanisms of bone induction. When implanted for posterolateral arthrodesis, rhOP-1 induces an intramembranous healing response, obviating the need for the cartilage intermediate phases found in endochondral bone development. The mechanism of increased speed and incidence of fusion using growth factors (rhOP-1) is delineated by this comprehensive study of preferential intramembranous ossification.     

Direct current electrical stimulation increases the fusion rate of spinal fusion cages

STUDY DESIGN: A randomized experimental evaluation of direct current stimulation in a validated animal model with an experimental control group, using blinded radiographic, biomechanical, histologic, and statistical measures. OBJECTIVES: To evaluate the efficacy of the adjunctive use of direct current stimulation on the fusion rate and speed of healing of titanium interbody fusion cages packed with autograft in a sheep lumbar interbody fusion model. SUMMARY OF BACKGROUND DATA: Titanium lumbar interbody spinal fusion cages have been reported to be 90% effective for single-level lumbar interbody fusion. However, fusion rates are reported to be between 70% and 80% in patients with multilevel fusions or with risk factors such as obesity, tobacco use, or metabolic disorders. The authors hypothesized that direct current stimulation would increase the fusion rate of titanium interbody fusion cages packed with autograft in a sheep lumbar interbody fusion model. METHODS: Twenty-two sheep underwent lumbar discectomy and fusion at L4-L5 with an 11- x 20-mm Bagby and Kuslich (BAK) cage packed with autograft. Seven sheep received a BAK cage and no current. Seven sheep had a cage and a 40-microA current applied with a direct current stimulator. Eight sheep had a BAK cage and a 100-microA current applied. All sheep were killed 4 months after surgery. The efficacy of electrical stimulation in promoting interbody fusion was assessed by performing radiographic, biomechanical, and histologic analyses in a blinded fashion. RESULTS: The histologic fusion rate increased as the direct current dose increased from 0 microA to 40 microA to 100 microA (P < 0.009). Histologically, all animals in the 100-microA group had fusions in both the right and left sides of the cage. Direct current stimulation had a significant effect on increasing the stiffness of the treated motion segment in right lateral bending (P < 0.120), left lateral bending (P < 0.017), right axial rotation (P < 0.004), left axial rotation (P < 0.073), extension (P < 0.078), and flexion (P < 0.029) over nonstimulated levels. CONCLUSION: Direct current stimulation increased the histologic and biomechanical fusion rate and the speed of healing of lumbar interbody spinal fusion cages in an ovine model at 4 months.     

Lumbar body fusion with a bioresorbable cage in a goat model is delayed by the use of a carboxymethylcellulose-stabilized collagenous rhOP-1 device.

The purpose of this study was to evaluate the efficacy of recombinant human osteogenic protein-1 (rhOP-1) with a carboxymethylcellulose-stabilized collagenous carrier as a bone graft substitute for instrumented lumbar spinal fusion in an established goat model. Twenty goats received a resorbable poly-L-lactic acid (PLLA) interbody cage packed with either rhOP-1 and its carrier or autologous bone graft. The carrier material was bovine collagen type-1 stabilized with carboxymethylcellulose. The fusion segments were retrieved at 3 or 6 months postimplantation and evaluated by radiographic and histologic analyses. The rhOP-1 graft substitute, used in combination with the resorbable PLLA cage, showed inferior results as compared to autologous bone graft in the goat lumbar fusion model. Whereas four out of five segments from the autograft group were fused after 6 months, none of the four segments receiving the rhOP-1 graft substitute were fused at this time point. Bone ingrowth into the cage was delayed or absent in the experimental group, whereas all autograft specimens showed advanced bone ingrowth (3 months) or fusion (6 months). We suggest that the fusion process was inhibited, because cells were unable to penetrate the rhOP-1 graft material. This led to delayed bone formation and in some cases inadequate tissue formation.     

Posterolateral and anterior interbody spinal fusion models in the sheep

Posterolateral and anterior interbody spinal arthrodesis is a frequent procedure, but high nonunion rates are reported and harvesting autologous bone graft from the iliac crest significantly increases morbidity. Bone graft substitutes are an alternative, but to date clinical results are not conclusive. Bone substitutes can be organic or inorganic, biologic or synthetic. They can have osteoconductive properties, inductive properties or both. Animal experiments are essential to investigating bone substitutes using biomechanical and histologic methods not available in clinical studies. Few authors reported on instrumented anterior fusion models, but none used the sheep model. In the current study posterolateral and anterior interbody fusion models in sheep are described. Both models used instrumented fusions, applying porous mineral scaffolds, alone or mixed with bone. The surgical techniques are described step-by-step and potential difficulties are highlighted. Preliminary results are reported for the posterolateral fusion model using coralline graft substitutes. The coral granules mixed with locally harvested bone had fusion outcomes similar to pure autologous bone. The graft substitute showed marked resorption between 12 and 20 weeks. All fusions had bone cortex and good trabecular connectivity. Histologic evaluation suggests after 20 weeks nearly the entire surface of the substitute is covered with new bone. Porous mineral bone substitutes mixed with locally harvested autologous bone are thought to be a valid alternative for posterolateral fusions.     

自体骨髓基质干细胞与钙磷陶瓷复合体在恒河猴腰椎前路融合中的实验研究

目的 评价自体骨髓基质干细胞（BMSCs）与钙磷生物陶瓷复合体的成骨效果。方法2003年3月至2005年4月,对9只成熟恒河猴行经腹膜外L3-4和L5-6腰椎间盘切除脊柱融合术。每只动物的两个脊柱节段随机接受3种治疗方法中的2种：自体髂骨移植（自体骨组,n=6）,空载体陶瓷移植物（陶瓷组,n=6）和骨髓基质干细胞-陶瓷复合体（BMSCs组,n=6）。自髂骨抽取骨髓,在含有成骨细胞诱导因子的培养液中体外扩增自体BMSCs,利用旋转培养方法构建骨髓基质干细胞-钙磷陶瓷复合体供移植用。实验动物在术后3个月处死,利用放射学、生物力学测试、组织学和组织形态计量学观察和分析脊柱融合节段。结果生物力学测试结果和组织学结果显示BMSCs组的椎体间脊柱融合效果明显好于陶瓷组;BMSCs组和自体骨组显示出近似的生物力学强度。BMSCs组和自体骨组的骨量显著多于陶瓷组;但陶瓷组的陶瓷材料残余量显著多于BMSCs组。结论在恒河猴椎体间脊柱融合模型中,自体骨髓基质干细胞和钙磷生物陶瓷复合体在移植入体内3个月内有良好的成骨并获得椎体间骨性融合。     

What bone graft substitutes should we use in post-traumatic spinal fusion?

Surgical treatment of spinal fractures consists of postural reduction and segmental arthrodesis, together with an eventual performance of spinal canal decompression. Spinal arthrodesis consists of the combination of a hardware system for mechanical stabilisation together with a biological substance for enhancement of bone formation. To date, autologous graft is the only biological substance demonstrated to possess osteogenic properties. Cancellous bone graft has greater cellular activity than cortical graft, whereas cortical graft is stronger. Consequently, according to biological and biomechanical properties of autograft, spinal posterior arthrodesis is better enhanced by cancellous autograft, whereas anterior interbody tricortical bone is more suitable for anterior fusion. Allograft does not cause harvesting complications as autograft does, and also its amount is theoretically unlimited; nevertheless the rate of bone fusion facilitated by allograft is far from that enhanced by autograft given that allograft has no osteoprogenitor cells. There is little evidence on the efficacy of demineralised bone matrix for spinal fusion. Bone morphogenetic proteins (BMPs) are in use in spinal surgery, but their exact role with respect to type, dose, and carrier, together with their cost-effectiveness, need further clinical delineation. Calcium phosphate compounds appear to be good as carriers; however, they have no osteoinductive or osteogenic properties. Current clinical literature seem to indicate their usefulness for bony fusion in spinal surgery, when combined with bone marrow aspirate or used as an extender for autologous bone graft. Age, length of fusion, location, and concurrent diseases should be definitive for fusion outcome; papers on spinal arthrodesis should neatly stratify these variables. Unfortunately, since that is not the rule, conclusions drawn from current literature are very unreliable. Autograft remains the gold standard, and cancellous bone is advisable in posterolateral approaches, whereas tricortical iliac crest autograft appears appropriate for interbody support. In longer segments, its expansion with BMPs looks safe at least. Basic knowledge has been achieved from animal experiments, and clinical application of the findings to humans should be done very cautiously; in any case, both anterior and posterior arthrodesis must be protected with instrumentation used according to appropriate biomechanical principles. A combination of failure of the correct graft together with proper instrumentation will result in poorer outcome, even if the right graft is used.     

Improved lumbar vertebral interbody fusion using rhOP-1: a comparison of autogenous bone graft, bovine hydroxylapatite (Bio-Oss), and BMP-7 (rhOP-1) in sheep

STUDY DESIGN: After disc removal and monosegmental instrumentation of the sheep lumbar spine, interbody fusion was compared for 6 months after administration of autogenous bone graft, hydroxylapatite, or rhOP-1. OBJECTIVE: To determine whether the use of rhOP-1 or hydroxylapatite would improve on the intercorporal fusion achieved by autologous bone grafting. SUMMARY OF BACKGROUND DATA: Spinal fusion often fails or shows loss of correction despite large-scale conventional techniques using posterior and anterior access. Also, additional operations to obtain bone grafts are required, which increase morbidity and strain for the patient, but do not always provide bone with sufficient primary stability and high osteogenic potential. METHODS: Vertebral fusion quality was examined by plain radiograph at 4-week intervals, by scintigraphy at 3 and 6 months, and by computed tomography scan, magnetic resonance imaging, biomechanical testing, and histologic evaluation. RESULTS: All examination methods demonstrated superior fusion after administration of rhOP-1, with radiologic fusion apparent at 4 months. Autologous bone grafts eventually produced bony healing in most cases, albeit of a lower quality than with rhOP-1. Hydroxylapatite use led only to the formation of a tight pseudarthrosis. CONCLUSIONS: The results indicate that rhOP-1 use is an appropriate method for improving interbody fusion in the sheep spine. In addition to offering the potential for improved bone healing, rhOP-1 use may permit less invasive surgery such as transpedicular fusion and the use of cages.     

Undercut macrostructure topography on and within an interbody cage improves biomechanical stability and interbody fusion

BACKGROUND CONTEXTThe interface and interactions between an interbody cage, graft material, and host bone can all participate in the fusion. Shortcomings of Poly(aryl-ether-ether-ketone) interbody cages have been addressed with novel titanium surfaces. Titanium surfaces paired with macroscale topography features on the endplates and within the aperture may provide additional benefits.PURPOSETo evaluate the influence of cage design parameters on interbody fusion in a large animal preclinical model.STUDY DESIGN/SETTINGA comparative preclinical large animal model was performed to evaluate how macroscale topography features of an interbody cage can facilitate early integration between the host bone, graft material, and interbody cage and these effects on biomechanical stability and fusion.METHODSForty single level interbody fusions (L4–L5) using iliac crest autograft and bilateral pedicle screw fixation were performed in adult sheep to evaluate the effect of undercut macrostructure topography features of an interbody cage on the endplates and within the aperture. Fusions were evaluated at 6 and 12 weeks (n=10 per group) using radiography, microcomputed tomography, biomechanical integrity, and histology endpoints.RESULTSThe presence of the undercut macrostructures present on the endplates and within the aperture statistically improved biomechanical integrity at 6 and 12 weeks compared with controls. Microcomputed tomography and histology demonstrated bony interdigitation within the endplate and aperture features contributing to the improvement in properties.CONCLUSIONSThe present study demonstrates that Poly(aryl-ether-ether-ketone) implants with titanium surfaces can be augmented by undercut macrostructures present on the endplates and within the aperture to provide opportunities for a series of anchoring points that, with new bone formation and remodelling, result in earlier and improved biomechanical integrity of the treated level.CLINICAL SIGNIFICANCEThis preclinical study showed that bone interdigitation with the undercut macrostructures present on the endplates and within the aperture resulted in improved fusion and biomechanical stability in a clinically relevant spinal fusion model. Future clinical study is warranted to evaluate such implants’ performance in humans.     

The biomechanical and histomorphometric properties of anterior lumbar fusions: a canine model

An in vivo model was developed to compare the biomechanical stability, incidence of radiographic union, bone formation rate, and bone graft remodeling parameters of anterior interbody fusions. Eighteen 1-year-old beagles underwent anterior and posterior spinal destabilization procedures at L5-L6 to produce a reproducible amount of spinal instability--resection of the anterior longitudinal ligament, L5-L6 intervertebral disk, L5 and L6 lamina, spinous processes, zygoopophyseal joints, and ligamentum flavum. Group I (N = 6) were surgically destabilized controls; Group II (N = 6) underwent anterior L5-L6 interbody fusion with iliac crest bone graft; and Group III (N = 6) underwent anterior stabilization with a longitudinal fibular strut graft in addition to the same operative procedure as Group II. Six months postoperatively the group with the highest incidence of successful radiographic L5-L6 arthrodesis was Group III, anterior interbody fusion and fibular stabilization (p less than .10). The rank order of biomechanical stability was the same for the three groups for both torsional and axial compressive stiffness, with Group I (destabilized controls) being the least rigid, then Group II (anterior fusion with iliac crest grafting only), and the most rigid to both torsion and axial compressive loading was Group III (anterior fusion with fibular stabilization and iliac crest bone graft). The bone formation rate [mm3/(mm3 x year) x 10(3)], which was derived from the distance between fluorochrome markers, revealed that the more stable the individual spinal construct, the lower the bone formation rate. In summary, the beagle provided a successful model for studying in vivo the response of anterior bone grafts over a 6-month interval and provided comparative biomechanical and histomorphometric data on spinal interbody fusion techniques.     

The 2002 Marshall Urist Young Investigator Award Paper. Lumbar arthrodesis gene expression: a comparison of autograft with osteogenic protein-1

Data from animals have revealed that osteogenic protein-1 induces solid intertransverse process fusion more reliably than autograft, and has motivated the question: What is the difference in the fusion bed environment engendered by the addition of osteogenic protein-1? To address this question, an established New Zealand White rabbit model of spinal arthrodesis was used to evaluate the effect of iliac crest autograft, and alternatively osteogenic protein-1, on cytokine gene expression in the developing spinal fusion mass. The autograft group and the osteogenic protein-1 group had a similar pattern of gene expression for most of the cytokines investigated, highlighting the finding that the application of one bone morphogenetic protein to the fusion bed results in nearly the same gene expression as that resulting from application of autologous bone. Some differences in cytokine expression were observed at the fusion bed with the addition of osteogenic protein-1. The increased level of expression of particular osteogenic, chondrogenic, and angiogenic growth factors at the later stages of fusion may be responsible for the improved rate of solid fusion with osteogenic protein-1 as compared with autograft alone. Sequences for bone morphogenetic protein-5 and bone morphogenetic protein-7 were determined, and their respective expression in the developing spinal fusion mass was observed for the first time.     

椎体间融合治疗腰椎间隙狭窄症的临床疗效分析

目的 分析各种椎体间融合术治疗椎间隙狭窄症的临床疗效,及其适应证。方法 采用后路全椎板减压椎体间植骨加节段内固定、后路全椎板减压双Cage植入或加用节段内固定、后路半椎板减压单Cage植入或加用节段内固定、前路椎体问撑开植骨及前路椎体间撑开双Cage植入等术式治疗腰椎间隙狭窄症84例并对疗效、适应证进行分析总结。结果 全部病例随访10-24个月,临床疗效优良率为90．5％,植骨融合率为91．7％(其中自体骨植骨融台率为84．0％,Cage植骨融合率为93．2％),椎问隙恢复高度为11．4mm(其中自体骨恢复高度为10．6mm,Cage恢复高度为11．8mm)。结论 椎体间植骨融合治疗椎间隙狭窄症具有疗效好、植骨融合率高等优点,根据不同病因选择不同术式治疗,能减少损伤、提高疗效、缩短康复时间．     

Beta-tricalcium phosphate combined with recombinant human bone morphogenetic protein-2: a substitute for autograft, used for packing interbody fusion cages in the canine lumbar spine

Beta-tricalcium phosphate (beta-TCP) combined with recombinant human bone morphogenetic protein-2 (BMP-2) was examined as a substitute for autograft for packing into interbody fusion cages in the canine lumbar spine model. Discectomy and interbody cage fusion were performed at three disc spaces in eight dogs. Examination of microradiographs and histological sections of the lumbar spine at 16 weeks postsurgery revealed three fusions in the autograft cages (Group A), three in the beta-TCP cages (Group B), and five in the beta-TCP-BMP-2 cages (Group C). The mean percentage of trabecular bone area in the cages was 51.9% in Group A, 48.8% in Group B, and 65.6% in Group C. Mean percentage of trabecular bone formation and mechanical stiffness were highest in the cages filled with beta-TCP and BMP-2. Combination of BMP to beta-TCP may act as an osteoconductive and osteoinductive bone graft substitute in clinical spine surgery.     

The role of supplemental translaminar screws in anterior lumbar interbody fixation: a biomechanical study

The immediate stabilization provided by anterior interbody cage fixation is often questioned. Therefore, the role of supplementary posterior fixation, particularly minimally invasive techniques such as translaminar screws, is relevant. The purpose of this biomechanical study was to determine the immediate three-dimensional flexibility of the lumbar spine, using six human cadaveric functional spinal units, in four different conditions: (1) intact, (2) fixed with translaminar screws (TLS), (3) instrumented with anterior interbody cage insertion with the BAK system and (4) instrumented with BAK cage with additional TLS fixation. Flexibility was determined in each testing condition by measuring the vertebral motions under applied pure moments (i.e. flexion-extension, bilateral axial rotation, bilateral lateral bending) in an unconstrained manner. Anterior fixation with the BAK alone provided significant stability in flexion and lateral bending. Additional posterior TLS significantly reduced the motion in extension and axial rotation. TLS fixation alone resulted in smaller rotations than BAK fixation in all loading directions. Based on these results, it seems that interbody cage fixation with the BAK system stabilizes the spine in some, but not all, loading directions. The problematic loading directions of extension and axial rotation can be substantially stabilized by using translaminar screw fixation. However, one should emphasize that the degree of stability needed to achieve solid fusion is not known. Received: 14 August 1997 Revised: 28 May 1998 Accepted: 9 June 1998     

Biomechanical evaluation of stand-alone interbody fusion cages in the cervical spine.

STUDY DESIGN: An in vitro biomechanical investigation of the immediate stability in cervical reconstruction. OBJECTIVES: The purpose of this study was to compare the segmental stability afforded by the interbody fusion cage, the anterior locking plate, and the "gold standard" autograft. SUMMARY OF BACKGROUND DATA: Recently, interbody fusion cage devices have been developed and used for cervical reconstruction, but to the authors' knowledge no studies have investigated the biomechanical properties of the stand-alone interbody cage device in the cervical spine. METHODS: Using six human cervical specimens, nondestructive biomechanical testing were performed, including axial rotation (+/-1.5 Nm, 50 N preload), flexion/extension (+/-1.5 Nm) and lateral bending (+/-1.5 Nm) loading modes. After C4-C5 discectomy, each specimen was reconstructed in the following order: RABEA cage (cage), tricortical bone graft (autograft), cervical spine locking plate system (plate). Unconstrained three-dimensional segmental range of motion at C4-C5 and above and below were evaluated. RESULTS: In flexion/extension, the plate demonstrated significantly lower range of motion than did the cage and the autograft (P < 0.005), and the cage showed a significantly higher range of motion than did the intact spine (P < 0.05). Under axial rotation, the plate indicated a significantly lower range of motion than did all other groups (P < 0.05). No significant differences were indicated in lateral bending. Adjacent to C4-C5, an increased range of motion was observed. CONCLUSIONS: The increased motion adjacent to C4-C5 may provide an argument for acceleration of disc degeneration. From the biomechanical point of view, this study suggests that the cervical interbody fusion cage should be supplemented with additional external or internal supports to prevent excessive motion in flexion-extension.     

The use of rhBMP-2 in interbody fusion cages. Definitive evidence of osteoinduction in humans: a preliminary report

STUDY DESIGN: A prospective randomized controlled human clinical pilot trial. OBJECTIVES: To determine the feasibility of using rhBMP-2/collagen as a substitute for autogenous bone graft inside interbody fusion cages to achieve arthrodesis in humans. SUMMARY OF BACKGROUND DATA: Preclinical studies have shown rhBMP-2 to be an effective substitute for autogenous bone graft, but there are no studies to date documenting such efficacy for human spine fusion. METHODS: Fourteen patients with single-level lumbar degenerative disc disease refractory to nonoperative management were randomized to receive lumbar interbody arthrodesis with a tapered cylindrical threaded fusion cage filled with rhBMP-2/collagen sponge or autogenous iliac crest bone. Patients were evaluated with radiographs, sagittally reformatted computed tomography scans, and Short Form-36 and Oswestry outcome questionnaires. RESULTS: All 11 patients who received rhBMP-2 were judged by three independent radiologists to have solid fusions (at 6, 12, and 24 months postimplantation), whereas only 2 of the 3 control patients, who received the standard treatment of autogenous iliac crest bone, were deemed to be fused. The Oswestry Disability Questionnaire scores of the rhBMP-2 group improved sooner (after 3 months) than those of the autograft group, with both groups demonstrating similar improvement at 6 months. Short Form 36 scores continued to improve up to 24 months. CONCLUSION: The arthrodesis was found to occur more reliably in patients treated with rhBMP-2-filled fusion cages than in controls treated with autogenous bone graft, although the sample size was limited. There were no adverse events related to the rhBMP-2 treatment. This study is one of the first to show consistent and unequivocal osteoinduction by a recombinant growth factor in-humans.     

Differences in early osteogenesis and bone micro-architecture in anterior lumbar interbody fusion with rhBMP-2, equine bone protein extract,and autograft

PurposeTo investigate the microstructural differences and responsible mechanisms in early bone formation in anterior lumbar interbody fusion (ALIF) in the spine using rhBMP-2 (INFUSE), equine bone protein extract (COLLOSS E) or autograft.MethodsTwelve Danish female landrace pigs underwent a 3-level ALIF procedure at L3–6. PEEK interbody cages packed with rhBMP-2, COLLOSS E, or autograft were inserted. The animals were divided into two groups of six, and observed for four and eight weeks postoperatively. μCT was performed for evaluation of microstructure of the bone within the cage. A mathematical finite element model was developed to investigate the aqueous behavior within the cages when exposed to external compressive forces.ResultsAt 4 weeks postoperative bone surface volume fraction (BS/TV) using rhBMP-2 was higher than with use of COLLOSS E and autograft, while trabecular thickness (Tb.Th.) was lower using rhBMP-2 at this time-point. At eight weeks BS/TV and trabecular number (Tb.N.) were still higher using rhBMP-2 than autograft and COLLOSS E. Connectivity density was significantly higher using rhBMP-2 than using autograft or COLLOSS E at both time-points. Between four- and eight-week time-points BV/TV and Tb.Th. rose while Tb.N. declined using rhBMP-2. The degree of anisotropy and the calculated amount of trabeculae with main direction along the spinal axis, were higher at four weeks using COLLOSS E. rhBMP-2 had the highest amount of trabeculae directed along the spinal axis at eight weeks. A change in main direction between four and eight weeks was observed for both autograft and rhBMP-2. The numerical results from the finite element model verify that significantly different flow pattern emerges as the boundary conditions are altered. At four weeks there was an evident correlation between trabecular orientation and flow pattern using rhBMP-2.ConclusionThis study reveals large differences in microstructure in the early osteogenesis and explains important mechanisms of early bone formation using rhBMP-2, COLLOSS E or autograft treatment. These differences might explain some of the unfortunate events reported such as edema, swelling, and excessive bone formation using different bone graft substitutes in spinal fusion procedures.     

The efficacy of a nanosynthetic bone graft substitute as a bone graft extender in rabbit posterolateral fusion

BACKGROUND CONTEXTSynthetic bone graft substitutes are commonly used in spinal fusion surgery. Preclinical data in a model of spinal fusion to support their efficacy is an important component in clinical adoption to understand how these materials provide a biological and mechanical role in spinal fusion.PURPOSETo evaluate the in vivo response of a nanosynthetic silicated calcium phosphate putty (OstP) combined with autograft compared to autograft alone or a collagen-biphasic calcium phosphate putty (MasP) combined with autograft in a rabbit spinal fusion model.STUDY DESIGNEfficacy of a nanosynthetic silicated calcium phosphate putty as an extender to autograft was studied in an experimental animal model of posterolateral spinal fusion at 6, 9, 12 and 26 weeks, compared to a predicate device.METHODSSkeletally mature female New Zealand White rabbits (70) underwent single level bilateral posterolateral intertransverse process lumbar fusion, using either autograft alone (AG), a nanosynthetic silicated calcium phosphate putty (OstP) combined with autograft (1:1), or a collagen-biphasic calcium phosphate putty (MasP) combined with autograft (1:1). Iliac crest autograft was harvested for each group, and a total of 2 cc of graft material was implanted in the posterolateral gutters per side. Fusion success was assessed at all time points by manual palpation, radiographic assessment, micro-CT and at 12 weeks only using non-destructive range of motion testing. Tissue response, bone formation and graft resorption were assessed by decalcified paraffin histology and by histomorphometry of PMMA embedded sections.RESULTSAssessment of fusion by manual palpation at the 12 week endpoint showed 7 out of 8 (87.5%) bilateral fusions in the OstP extender group, 4 out of 8 (50%) fusions in the MasP extender group, and 6 out of 8 (75%) fusions in the autograft alone group. Similar trends were observed with fusion scores of radiographic and micro-CT data. Histology showed a normal healing response in all groups, and increased bone formation in the OstP extender group at all timepoints compared to the MasP extender group. New bone formed directly on the OstP granule surface within the fusion mass while this was not a feature of the Collagen-Biphasic CaP material. After 26 weeks the OstP extender group exhibited 100% fusions (5 out of 5) by all measures, whereas the MasP extender group resulted in bilateral fusions in 3 out of 5 (60%), assessed by manual palpation, and fusion of only 20 and 0% by radiograph and micro-CT scoring, respectively. Histology at 26 weeks showed consistent bridging of bone between the transverse processes in the Ost P extender group, but this was not observed in the MasP extender group.CONCLUSIONSThe nanosynthetic bone graft substituted studied here, used as an extender to autograft, showed a progression to fusion between 6 and 12 weeks that was similar to that observed with autograft alone, and showed excellent fusion outcomes, bone formation and graft resorption at 26 weeks.CLINICAL SIGNIFICANCEThis preclinical study showed that the novel nanosynthetic silicated CaP putty, when combined with autograft, achieved equivalent fusion outcomes to autograft. The development of synthetic bone grafts that demonstrate efficacy in such models can eliminate the need for excessive autograft harvest and results from this preclinical study supports their effective use in spinal fusion surgery.     

Outcomes of posterolateral versus BAK titanium cage interbody lumbar fusion in injured workers: a retrospective cohort study

Lumbar fusion has been criticized for variable patient outcomes, though little is known regarding how outcomes vary across procedures. We examined outcomes of posterolateral versus BAK interbody lumbar fusion in workers' compensation cases. A medical record review and a follow-up survey were completed. The sample included 185 posterolateral and 185 lumbar interbody fusions. An outcome survey was conducted an average of 5 years after surgery. Arthrodesis rates, satisfaction, function, and health were better for the BAK interbody lumbar fusion cohort. Results suggest greater efficacy of the BAK interbody approach over posterolateral approaches to lumbar fusion in compensated patients.     

Healing of segmental bone defects with granular porous hydroxyapatite augmented with recombinant human osteogenic protein-1 or autologous bone marrow.

Hydroxyapatite is a synthetic bone graft, which is used for the treatment of bone defects and nonunions. However, it is a rather inert material with no or little intrinsic osteoinductive activity. Recombinant human osteogenic protein-1 (rhOP-1) is a very potent biological agent, that enhances osteogenesis during bone repair. Bone marrow contains mesenchymal stem cells, which are capable of new bone formation. Biosynthetic bone grafts were created by the addition of rhOP-1 or bone marrow to granular porous hydroxyapatite. The performance of these grafts was tested in a sheep model and compared to the results of autograft, which is clinically the standard treatment of bone defects and nonunions. A 3 cm segmental bone defect was made in the tibia and fixed with an interlocking intramedullary nail. There were five treatment groups: no implant (n=6), autograft (n=8), hydroxyapatite alone (n=8), hydroxyapatite loaded with rhOP-1 (n=8), and hydroxyapatite loaded with autologous bone marrow (n=8). At 12 weeks, healing of the defect was evaluated with radiographs, a torsional test to failure, and histological examination of longitudinal sections through the defect. Torsional strength and stiffness of the healing tibiae were about two to three times higher for autograft and hydroxyapatite plus rhOP-1 or bone marrow compared to hydroxyapatite alone and empty defects. The mean values of both combination groups were comparable to those of autograft. There were more unions in defects with hydroxyapatite plus rhOP-1 than in defects with hydroxyapatite alone. Although the differences were not significant, histological examination revealed that there was more often bony bridging of the defect in both combination groups and the autograft group than in the group with hydroxyapatite alone. Healing of bone defects, treated with porous hydroxyapatite, can be enhanced by the addition of rhOP-1 or autologous bone marrow. The results of these composite biosynthetic grafts are equivalent to those of autograft.     

Transforaminal lumbar interbody fusion: surgical technique and results in 24 patients

OBJECTIVE: The advantage of anterior column support and fusion in addition to pedicle fixation in patients with degenerative spinal disorders has become increasingly clear. With the increase in popularity of this treatment, a variety of techniques have been used to achieve the goal of anterior column support, fusion, and segmental instrumentation. Posterior lumbar interbody fusion has been used since the late 1940s in the treatment of degenerative lumbar spine. We evaluated a modification to posterior lumbar interbody fusion called transforaminal lumbar interbody fusion (TLIF). METHODS: A retrospective analysis was performed on 24 patients (9 women, 15 men) who underwent TLIF. The approach involved a unilateral laminectomy and inferior facetectomy at the level of fusion. The interbody fusion was achieved from this unilateral approach by performing discectomy, arthrodesis, and insertion of one or two titanium cages packed with autologous bone. The average age of the patients in this study was 42.6 +/- 12.5 years. Five patients were smokers. Five cases were related to workmen's compensation. Seventeen patients' original symptoms were a combination of low back pain and radiculopathy. Ten patients had had a previous spine operation. RESULTS: Eleven patients had L4-S1 TLIFs. The rest of the patients had a single-level TLIF (L2-S1). Average intensive care unit and floor days were 1.1 +/- 1.0 and 5.8 +/- 2.2 days, respectively. The number of days to ambulation was 2.8 +/- 1.6 days. There were a total of six self-limited complications in 24 patients (including one transient neurological complication). The average follow-up time was 16.9 +/- 9.1 months. Twenty-two patients had solid fusions. A modified Prolo scale (4 worst, 20 best) was used to evaluate the clinical outcome. The average score was 16.1 +/- 4.1. CONCLUSION: TLIF is a reliable and safe technique for interbody support that can be performed with excellent clinical outcome. In the authors' experience, TLIF offers excellent exposure with minimal risk. This applies particularly in cases of repeat spine surgery, in which the presence of scar tissue makes traditional posterior lumbar interbody fusion techniques difficult or impossible. In addition, TLIF seems to be a viable alternative to anteroposterior circumferential fusion and/or anterior lumbar interbody fusion.