Augmenting local bone with Grafton demineralized bone matrix for posterolateral lumbar spine fusion: avoiding second site autologous bone harvest

Mineralization and integrity of the bone graft mass were evaluated among patients having posterolateral fusion. Grafting consisted of a composite of Grafton and "local" autologous bone (n=56) or iliac crest autograft alone (n=52). Mineralization was rated radiographically at baseline and at 3, 6, 12, and 24 months. Integrity was judged as fused or not fused. Mineralization ratings did not differ significantly between groups at any postoperative interval (P values of .25-1.00). The percentage of patients fused was similar in both groups (60% and 56% for Grafton and controls, respectively; P=.83). Fifteen control patients reported donor site pain. These findings warrant further evaluation of this composite.     

Evaluation of a new formulation of demineralized bone matrix putty in a rabbit posterolateral spinal fusion model

Background contextAlternatives to autologous bone graft (ABG) with osteoconductive, osteoinductive, and osteogenic potential continue to prove elusive. Demineralized bone matrix (DBM) however, with its osteoconductive and osteoinductive potential remains a viable option to ABG in posterolateral spine fusion.PurposeTo compare the efficacy of a new formulation of DBM putty with that of ABG in a rabbit posterolateral spinal fusion model.Study designEfficacy of a new formulation of DBM was studied in an experimental animal posterolateral spinal fusion model.MethodsTwenty-four male New Zealand White rabbits underwent bilateral posterolateral spine arthrodesis of the L5–L6 intertransverse processes, using either ABG (control group, n=12) or DBM (DBM made from rabbit bone) putty (test group, n=12). The animals were killed 12 weeks after surgery and the lumbar spines were excised. Fusion success was evaluated by manual palpation, high resolution X-rays, microcomputed tomography imaging, biomechanical four-point bending tests, and histology.ResultsTwo animals were lost because of anesthetic related issues. Manual palpation to assess fusion success in the explanted lumbar spines showed no statistical significant difference in successful fusion in 81.8% (9/11) of DBM group and 72.7% (8/11) of ABG group (p=.99). Reliability of these assessments was measured between three independent observers and found near perfect agreement (intraclass correlation cofficient: 0.92 and 0.94, respectively). Fusion using high resolution X-rays was solid in 10 of the DBM group and 9 of the ABG group (p=.59). Biomechanical testing showed no significant difference in stiffness between the control and test groups on flexion, extension, and left lateral and right lateral bends, with p values accounting for .79, .42, .75, and .52, respectively. The bone volume/total volume was greater than 85% in the DBM treated fusion masses. Histologic evaluation revealed endochondral ossification in both groups, but the fusion masses were more mature in the DBM group.ConclusionsThe DBM putty achieved comparable fusion rates to ABG in the rabbit posterolateral spinal fusion model.     

Demineralized bone matrix composite grafting for posterolateral spinal fusion

In a prospective series, the 24-month fusion status was evaluated radiographically among patients undergoing instrumented posterolateral lumbosacral spinal fusion. Seventy-three patients had a diagnosis of degenerative disk disease or degenerative spondylolisthesis and had supplemental bone grafting with demineralized bone matrix (DBM) putty (Grafton DBM; Osteotech, Eatontown, NJ) enriched with aspirated bone marrow (DBM bone marrow), DBM putty combined with iliac crest autograft (DBM autograft), or autograft. Overall, approximately 63% (12 of 19) of DBM bone marrow, 70% (19 of 27) of DBM autograft, and 67% (18 of 27) of autograft patients were fused at 24 months (P = .875). These findings suggest that both DBM composites offer similar performance to autograft in posterolateral spinal fusion.     

Use of demineralized bone matrix in spinal fusion

Spinal fusion remains the gold-standard treatment for several pathological spine conditions. Although, autologous Iliac Crest Bone Grafting is considered the gold-standard graft choice to promote spinal fusion; however, it is associated with significant donor site morbidity and a limited graft quantity. Therefore, several bone graft alternatives have been developed, to augment arthrodesis. The purpose of this review is to present the results of clinical studies concerning the use of demineralized bone matrix (DBM), alone or as a composite graft, in the spinal fusion. A critical review of the English-language literature was conducted on Pubmed, using key word “demineralized bone matrix”, “DBM”, “spinal fusion”, and “scoliosis”. Results had been restricted to clinical studies. The majority of clinical trials demonstrate satisfactory fusion rates when DBM is employed as a graft extender or a graft enhancer. Limited number of prospective randomized controlled trials (4 studies), have been performed comparing DBM to autologous iliac crest bone graft in spine fusion. The majority of the clinical trials demonstrate comparable efficacy of DBM when it used as a graft extender in combination with autograft, but there is no clinical evidence to support its use as a standalone graft material. Additionally, high level of evidence studies are required, in order to optimize and clarify the indications of its use and the appropriate patient population that will benefit from DBM in spine arthrodesis.     

New formulations of demineralized bone matrix as a more effective graft alternative in experimental posterolateral lumbar spine arthrodesis

STUDY DESIGN: A rabbit model of posterolateral intertransverse process spine arthrodesis was used. OBJECTIVE: To determine the efficacy of two new formulations of demineralized bone matrix. SUMMARY OF BACKGROUND DATA: The flowable gel form of Grafton (Osteotech, Eatontown, NJ) demineralized bone matrix has been shown to have osteoinductive properties in various models and currently is used clinically as bone graft material in posterolateral lumbar spine arthrodesis. Two new formulations of Grafton, one made of flexible sheets (Flex) and the other made in a malleable consistency (Putty), have improved handling characteristics compared with the gel form. METHODS: In this study, 108 New Zealand white rabbits underwent bilateral posterolateral intertransverse spine arthrodesis at L5-L6 using autogenous iliac crest bone graft alone (control), one of the new forms of demineralized bone matrix (DBM; made from rabbit bone) alone or in combination with autogenous iliac crest bone. Rabbits were killed 6 weeks after surgery. The lumbar spines were excised, and fusion success or failure was determined by manual palpation and radiography. Specimens also were processed for undecalcified histologic analysis. RESULTS: Manual palpation of the harvested lumbar spines revealed that the fusion rates of the Flex-DBM/Auto group (9/9, 100%) and Putty-DBM/Auto group (10/10, 100%) were superior (P < 0.01) to those of the Auto/control group (3/9, 33%). As a stand-alone graft substitute, Flex-DBM performed superiorly with a fusion rate of 11/11 (100%) compared with that of Putty-DBM (10/12, 83%) and Gel-DBM (7/12, 58%). The devitalized version of Flex-DBM had a fusion rate of 4/11 (36%), which was comparable with the devitalized Putty-DBM rate of 4/12 (33%). Both were superior (P < 0.05) to the devitalized Gel-DBM rate of 0/12 (0%). More mature fusions with greater amounts of trabecular bone were present radiographically and histologically in rabbits that received all forms of demineralized bone matrix than in those in which autograft was used. CONCLUSIONS: The new flexible sheet and malleable putty forms of demineralized bone matrix were effective as graft extender and graft enhancer in a model of posterolateral lumbar spine fusion. These newer formulations of Grafton appear to have a greater capacity to form bone than the gel form or autogenous bone graft alone in this model.     

A comparison of commercially available demineralized bone matrix for spinal fusion

In an effort to augment the available grafting material as well as to increase spinal fusion rates, the utilization of a demineralized bone matrix (DBM) as a graft extender or replacement is common. There are several commercially available DBM substances available for use in spinal surgery, each with different amounts of DBM containing osteoinductive proteins. Each product may have different osteoinductivity potential due to different methods of preparation, storage, and donor specifications. The purpose of this study is to prospectively compare the osteoinductive potential of three different commercially available DBM substances in an athymic rodent spinal fusion model and to discuss the reasons of the variability in osteoinductivity. A posterolateral fusion was performed in 72 mature athymic nude female rats. Three groups of 18 rats were implanted with 1 of 3 DBMs (Osteofil, Grafton, and Dynagraft). A fourth group was implanted with rodent autogenous iliac crest bone graft. The rats were sacrificed at 2, 4, 6, and 8 weeks. A dose of 0.3 cm³ per side (0.6 cm³per animal) was used for each substance. Radiographs were taken at 2 weeks intervals until sacrifice. Fusion was determined by radiographs, manual palpation, and histological analysis. The Osteofil substance had the highest overall fusion rate (14/18), and the highest early 4 weeks fusion rate of (4/5). Grafton produced slightly lower fusion rates of (11/17) overall, and lower early 4 weeks fusion rate of (2/5). There was no statistically significant difference between the rate of fusion after implantation of Osteofil and Grafton. None of the sites implanted with Dynagraft fused at any time point (0/17), and there was a significantly lower fusion rate between the Dynagraft and the other two substances at the six-week-time point and for final fusion rate (P = 0.0001, Fischer’s exact test). None of the autogenous iliac crest animals fused at any time point. Non-decalcified histology confirmed the presence of a pseudarthrosis or the presence of a solid fusion, and the results were highly correlated with the manual testing. Although all products claim to have significant osteoinductive capabilities, this study demonstrates that there are significant differences between some of the tested products.     

Autograft versus allograft with or without demineralized bone matrix in posterolateral lumbar fusion in rabbits. Laboratory investigation

OBJECT: Posterolateral spinal fusions are performed to treat different spinal disorders. Autograft continues to be the gold standard; it is, however, associated with donor site morbidity and limited sources. Allograft has been used, but has been reported to result in lower fusion rates. Demineralized bone matrix (DBM) has also been used and reportedly increases the fusion rate in a variety of critical defect models. Different forms of DBM are available, not all have been independently studied. To evaluate the effect of a xenogenic DBM added to allograft on the fusion rate of posterolateral lumbar spine arthrodesis the authors designed an experimental study comparing posterolateral fusion rate using autograft, allograft, and allograft plus a xenogenic DBM in a validated animal model. METHODS: A bilateral, 1-level (L4-5) intertransverse process fusion was performed in 45 male New Zealand rabbits. Iliac crest bone graft was harvested bilaterally from each rabbit. The rabbits were randomly assigned to 3 groups: Group I, Autograft, 15 rabbits; Group II, Allograft, 15 rabbits; and Group III, Allograft plus DBM in a paste form (Dynagraft). The animals were killed 8 weeks after surgery. Fusion was assessed radiographically and by manual palpation by 2 independent observers. The results were analyzed using the Fisher exact test and chi-square test. RESULTS: The fusion rate was 46.6% (7 of 15 rabbits) in the autograft group, 33.3% (5 of 15 rabbits) in the allograft group, and 33.3% (5 of 15 rabbits) in the allograft plus DBM group (p > 0.05). CONCLUSIONS: Autograft produced a higher fusion rate than allograft in this spinal fusion rabbit model, but the difference was not statistically significant. Allograft plus xenogenic DBM showed the same fusion rate as allograft alone.     

Instrumented posterolateral lumbar fusion using coralline hydroxyapatite with or without demineralized bone matrix, as an adjunct to autologous bone.

BACKGROUND CONTEXT: Autogenous posterolateral fusion with and without instrumentation has been reported with good results. However, difficult-to-fuse patients, such as smokers, elderly patients with poor bone quality and/or quantity, or patients with prior posterior surgeries, may have somewhat lower fusion rates. PURPOSE: To determine the efficacy of coralline hydroxyapatite with or without demineralized bone matrix as a bone graft extender in a human clinical model with long-term follow-up. STUDY DESIGN/SETTING: A retrospective series of 40 patients undergoing instrumented autogenous posterolateral lumbar fusion augmented with coralline hydroxyapatite with or without demineralized bone matrix. PATIENT SAMPLE: Long-term clinical and radiographic follow-up were examined for 40 patients who underwent an instrumented posterolateral fusion only. Patients undergoing anterior lumbar interbody fusion (ALIF) procedures were not considered part of the sample. METHODS: All patients underwent successful transpedicular fixation with autogenous posterolateral lumbar fusion. Fifteen cc of Pro Osteon 500 coralline hydroxyapatite (Interpore Cross International, Irvine, CA) was used at each level. An additional 10 cc of Grafton demineralized bone matrix gel (Osteotech, Eatontown, NJ) was used in 70% of these patients. RESULTS: An overall fusion rate of 92.5% was achieved. Pain and function improvement were good but somewhat age dependent and correlated with the number of comorbidities. Patients with Grafton DBM gel had a lower fusion rate of 89.3%. CONCLUSIONS: Based on this small retrospective review, coralline hydroxyapatite is an effective bone graft extender in difficult-to-fuse patients as an adjunct to autologous bone for posterolateral fusion of the lumbar spine when combined with rigid instrumentation.     

Posterolateral lumbar spine fusion using a novel demineralized bone matrix: a controlled case pilot study

Introduction

Intertransverse posterolateral fusion along with instrumentation is a common technique used for spinal fusion. Iliac crest bone graft (ICBG) offers good fusion success rates with a low risk for disease transmission but is, however, linked with certain morbidity. In an effort to eliminate or reduce the amount of iliac graft needed, bone substitutes including demineralized bone matrix (DBM) have been developed. This study evaluates a novel DBM (Accell Connexus^®) used in one or two-level instrumented posterolateral lumbar fusion.

Materials and methods

A total of 59 consecutive patients were studied as two groups. Group 1 consisted of 33 patients having Accell Connexus^® used to augment either ICBG or local decompression material. Group 2 consisted of 26 consecutive patients, operated prior to the introduction of this novel DBM, having either ICBG alone or local decompression material. Fusion was assessed by two independent observers, blinded to graft material, using standardized criteria found in the literature. All adverse events were recorded prospectively.

Results

The results show no statistically significant differences between the two groups in fusion rates, complications, surgery duration, ODI, or pain on VAS. Logistical regression showed no relation between fusion and age, smoking status or comorbidities. Furthermore, no adverse events related to the use of the novel DBM were observed.

Conclusion

The results from this study demonstrate that the novel DBM presented performs equally as well as that of autologous bone, be it either ICBG or a local decompression material, and can therefore be used as a graft extender.

     

Opioids delay healing of spinal fusion: a rabbit posterolateral lumbar fusion model

Background Context

Opioid use is prevalent in the management of pre- and postoperative pain in patients undergoing spinal fusion. There is evidence that opioids downregulate osteoblasts in vitro, and a previous study found that morphine delays the maturation and remodeling of callus in a rat femur fracture model. However, the effect of opioids on healing of spinal fusion has not been investigated before. Isolating the effect of opioid exposure in humans would be limited by the numerous confounding factors that affect fusion healing. Therefore, we have used a well-established rabbit model to study the process of spinal fusion healing that closely mimics humans.

Implants of heterologous demineralized bone matrix for induction of posterior spinal fusion in rats.

The authors tested the osteoinductive capacity of powdered heterologous (bovine) demineralized bone matrix in rats. The first part of the study concerned a monolateral posterior spinal implant after decortication of three vertebrae, using as a control area the animal's contralateral side, in which neither bone graft nor any other material were placed. In another group of rats, a comparative evaluation was made of powdered heterologous demineralized bone matrix and fresh autologous bone. In the same animal, autologous bone was implanted to realize a thoracic posterior fusion and demineralized bone matrix, to induce a posterior fusion in the lumbar area. All data obtained suggested a good osteoinductive activity of heterologous powdered demineralized bone matrix. The two posterior spinal fusions done in the same animal with heterologous demineralized bone matrix or autologous bone, respectively, had similar callus development and required the same time for formation.     

Use of biphasic calcium phosphate versus demineralized bone matrix: retrospective clinical and CT analysis of posterolateral fusion results

Purpose

Bone graft extenders have been developed to prevent donor site morbidity associated with iliac crest bone graft, but few studies compared the efficacy of various substitutes. Our purpose was to determine fusion rate and clinical outcome in patients undergoing lumbar arthrodesis using demineralized bone matrix (DBM) and biphasic calcium phosphate (BCP).

Methods

Patients with degenerative spondylolisthesis undergoing one-level or two-level arthrodesis of lumbar spine were retrospectively reviewed. Two treatment groups placed either BCP or DBM, in addition to local autograft in lumbar posterolateral space. Three-dimensional CT exam and dynamic flexion–extension radiographs at postoperative 2-year were assessed for posterolateral fusion status and pain scale and Oswestry Disability Index (ODI) for clinical outcome.

Results

Of the 148 patients reviewed (including 23 in one- and 58 patients in two-level in BCP group, and 47 in one- and 20 patients in two-level in DBM group), no significant differences were found in terms of age, sex, BMI, smoking, diabetes, steroids, number of level fused, non-union rate or revision surgery between BCP and DBM groups. Significantly improved pain scale of back and leg and ODI were found in both groups postoperatively without group difference. We found a comparable fusion rate in one-level surgery (100% versus 93.6%) and a superior fusion rate of BCP group in two-level surgery (98.3% versus 80.0%, p = 0.01).

Conclusion

Being a bone graft extender without osteoinductive property, with local autograft, BCP is comparable to DBM for one- and superior for two-level fusion. No significant difference was found in clinical outcomes.

     

Efficacy comparison of Accell Evo3 and Grafton demineralized bone matrix putties against autologous bone in a rat posterolateral spine fusion model

Background Context

Spinal fusion procedures are intended to stabilize the spinal column for a multitude of disorders including abnormal curvature, traumatic instability, degenerative instability, and damage from infections or tumors. As an aid in the bone healing response, bone graft materials are used to bridge joints for arthrodesis and promote unions in pseudoarthrosis. Currently, the gold standard for stabilizing fusion masses in spinal procedures involves using the osteogenic, osteoinductive, and osteoconductive properties of autologous iliac crest corticocancellous bone. However, considerable morbidity is associated with harvesting the autologous graft. Donor site complications including infection, large hematomas, and pain have been reported at rates as high as 50% (Boden and Jeffrey, 1995). Biologically, the rate of bone repair dictates the rate at which the fusion mass will unite under autologous graft conditions.

Response of bone marrow stroma cells to demineralized cortical bone matrix in experimental spinal fusion in rabbits

The effect of autogeneic bone marrow (BM) cells and allogeneic demineralized bone matrix (DBM), alone or combined, as transplantation materials was studied in an experimental posterior thoracic spinal fusion model in rabbits. Transplantation of composite grafts composed of BM and DBM showed the first signs of fusion between two spinal segments after four weeks, reaching 86% after 20 weeks. Late fusion results achieved with DBM alone were similar. The capacity of BM per se to build up a spinal fusion was insignificant. Calcified tissue, documented roentgenographically, was shown to develop locally with time, and the earliest bridging of an interspace was noted after four weeks. Histologically, formation of new bone and cartilage was observed after two weeks, showing mature lamellar bone formation between thoracic segments after 20 weeks. Furthermore, increased 45Ca activity was still observed in the fused tissues after 20 weeks. Although, with grafting materials used, this model for experimental spinal fusion gave promising results, further investigations with other fusion techniques could give still better effects.     

成骨细胞复合异种脱蛋白骨进行腰椎后外侧融合

目的 评价兔皮质骨来源的成骨细胞复合异种脱蛋白骨进行脊柱融合的效果.方法选取60只新西兰兔随机分4组行腰椎后外侧融合术:Ⅰ组,组织工程骨组;Ⅱ组,空白对照组;Ⅲ组,单纯异种脱蛋白骨组;Ⅳ组,自体髂骨组.术后10周将动物处死做大体观察、手工力学、X线片、CT和组织学检查.结果大体观察、手工力学、X线片及CT检查均显示Ⅰ、...     

Interaction of allogeneic demineralized bone matrix and porous hydroxyapatite bioceramics in lumbar interbody fusion in rabbits

Bone repair by autograft is effective in clinical practice. However, serious problems arise when a considerable volume of transplant is needed, as with spinal fusion procedures. The use of bone substitutes combined with osteoinductive agents may contribute to the solution of such problems. In this study, the effectiveness of such a procedure was tested in an experimental model of interbody fusion in rabbits in which the incorporation of a porous hydroxyapatite block (HA) was enhanced by the addition of allogeneic demineralized bone matrix (DBM). The latter was used as a delivery system for the osteoinductive activity of the bone morphogenetic protein contained in the matrix. A group implanted with combined HA + DBM showed significantly earlier stabilization of the fusion when compared to groups implanted with DBM alone, HA alone, and bone autografts. On the other hand, the general results of the fusion with HA + DBM were superimposable on those of autografts. With further research, the combination of a bone substitute and an osteoinductive agent may constitute an alternative to the use of bone autografts.