Bone graft substitutes for spine fusion: A brief review

Bone graft substitutes are widely used in the field of orthopedics and are extensively used to promote vertebral fusion. Fusion is the most common technique in spine surgery and is used to treat morbidities and relieve discomfort. Allograft and autograft bone substitutes are currently the most commonly used bone grafts to promote fusion. These approaches pose limitations and present complications to the patient. Numerous alternative bone graft substitutes are on the market or have been developed and proposed for application. These options have attempted to promote spine fusion by enhancing osteogenic properties. In this review, we reviewed biology of spine fusion and the current advances in biomedical materials and biological strategies for application in surgical spine fusion. Our findings illustrate that, while many bone graft substitutes perform well as bone graft extenders, only osteoinductive proteins (recombinant bone morphogenetic proteins-2 and osteogenic protein-1) provide evidence for use as both bone enhancers and bone substitutes for specific types of spinal fusion. Tissue engineered hydrogels, synthetic polymer composites and viral based gene therapy also holds the potential to be used for spine fusion in future, though warrants further investigation to be used in clinical practice.     

Clinical applications of BMP-7/OP-1 in fractures,nonunions and spinal fusion

Since the identification of the osteogenic protein-1 (OP-1) gene, also called bone morphogenetic protein-7 (BMP-7), almost 20 years ago, OP-1 has become one of the most characteristic members of the BMP family. The biological activity of recombinant human OP-1 has been defined using a variety of animal models. These studies have demonstrated that local implantation of OP-1 in combination with a collagen matrix results in the repair of critical size defects in long bones and in craniofacial bones and the formation of bony fusion masses in spinal fusions. Clinical trials investigating long bone applications have provided supportive evidence for the use of OP-1 in the treatment of open tibial fractures, distal tibial fractures, tibial nonunions, scaphoid nonunions and atrophic long bone nonunions. Clinical studies investigating spinal fusion applications have provided supportive evidence for the use of OP-1 in posterolateral lumbar models and compromised patients as an adjunct or as a replacement for autograft. Both long bone repair and spinal fusion studies have demonstrated the efficacy and safety of OP-1 by clinical outcomes and radiographic measures. Future clinical investigations will be needed to better define variables, such as dose, scaffold and route of administration. Clearly the use of BMPs in orthopaedics is still in its formative stage, but the data suggest an exciting and promising future for the development of new therapeutic applications.     

A pilot safety and efficacy study of OP-1 putty (rhBMP-7) as an adjunct to iliac crest autograft in posterolateral lumbar fusions

The ability of bone morphogenetic proteins (BMPs) to induce bone formation has led to an increasing interest in the potential for their use in fusion surgery. The purpose of this multi-center clinical pilot study was to evaluate the safety of one such BMP—osteogenic protein 1, in the form of OP-1 putty—combined with autograft for intertransverse process fusion of the lumbar spine in patients with symptomatic spinal stenosis and degenerative spondylolisthesis following spinal decompression. Twelve patients with spinal stenosis and degenerative lumbar spondylolisthesis underwent laminectomy and partial or complete medial facetectomy as required for decompression of the neural elements followed by intertransverse process fusion by placing iliac crest autograft and OP-1 putty between the decorticated transverse processes. No instrumentation was used. Patients were followed clinically using the Oswestry scale and radiographically using static and dynamic radiographs to assess their fusion status. Independent and blinded radiologists assessed the films for the presence of bridging bone between the transverse processes and measured translation and angulation on dynamic films using digital calipers. In addition to bridging bone, less than or equal to 5° of angular motion and less than or equal to 2 mm of translation were required to classify the patients as successfully fused, as per the definition of successful fusion provided by the FDA for use in clinical trials involving investigational devices to attain spinal fusion. Radiographic outcome was compared to a historical control (autograft alone fusion without instrumentation for the treatment of degenerative spondylolisthesis). All adverse events were recorded prospectively. The results showed 9 of the 12 patients (75%) obtained at least a 20% improvement in their preoperative Oswestry score, while 6 of 11 patients (55%) with radiographic follow-up achieved a solid fusion by the criteria used in this study. Bridging bone on the anteroposterior film was observed in 10 of the 11 patients (91%). No systemic toxicity, ectopic bone formation, recurrent stenosis or other adverse events related to the OP-1 putty implant were observed. A successful fusion was observed in slightly over half the patients in this study, using stringent criteria without adjunctive spinal instrumentation. This study did not demonstrate the superiority of OP-1 combined with autograft over an autograft alone historical control, in which the fusion rate was approximately 45%. The lack of adverse events related to the OP-1 putty implant in this study is in agreement with other studies supporting the safety of bone morphogenetic proteins in spinal surgery.     

A 2-year follow-up pilot study evaluating the safety and efficacy of op-1 putty (rhbmp-7) as an adjunct to iliac crest autograft in posterolateral lumbar fusions

The ability of bone morphogenetic proteins (BMPs) to induce bone formation has led to a multitude of investigations into their use as bone graft substitutes in spinal surgery. The purpose of this multi-center clinical pilot study was to evaluate the safety and efficacy of BMP-7 (osteogenic protein 1, OP-1), in the form of a putty, combined with autograft for intertransverse process fusion of the lumbar spine in patients with symptomatic spinal stenosis and degenerative spondylolisthesis following spinal decompression. Twelve patients with spinal stenosis and degenerative lumbar spondylolisthesis underwent a laminectomy and partial or complete medial facetectomy as required for decompression of the neural elements, followed by an intertransverse process fusion by placing iliac crest autograft and OP-1 putty between the decorticated transverse processes. No instrumentation was used. Patients were followed clinically using the Oswestry scale and SF-36 outcome forms, and radiographically using static and dynamic radiographs to assess their fusion status over a 2-year period. Independent and blinded radiologists assessed the films for the presence of bridging bone between the transverse processes and measured translation and angulation on dynamic films using digital calipers. Radiographic outcome was compared to a historical control (autograft alone fusion without instrumentation for the treatment of degenerative spondylolisthesis). All adverse events were recorded prospectively. The results showed eight of the nine evaluable patients (89%) obtained at least a 20% improvement in their preoperative Oswestry score, while five of ten patients (50%) with radiographic follow-up achieved a solid fusion by the criteria used in this study. Bridging bone on the anteroposterior film was observed in seven of the ten patients (70%). No systemic toxicity, ectopic bone formation, recurrent stenosis or other adverse events related to the OP-1 putty implant were observed. A successful fusion was observed in slightly over half the patients in this study, using stringent criteria without adjunctive spinal instrumentation. This study did not demonstrate the statistical superiority of OP-1 combined with autograft over an autograft alone historical control, in which the fusion rate was 45%. There were no adverse events related to the OP-1 putty implant in this study, which supports findings in other studies suggesting the safety of bone morphogenetic proteins in spinal surgery.     

Osteogenic protein versus autologous interbody arthrodesis in the sheep thoracic spine. A comparative endoscopic study using the Bagby and Kuslich interbody fusion device

STUDY DESIGN: Using an in vivo interbody arthrodesis model, the efficacy of the Bagby and Kuslich (BAK) device packed with recombinant human osteogenic protein-1 (rhOP-1) was evaluated. OBJECTIVES: To compare the efficacy of osteogenic protein with that of autograft for interbody arthrodesis, with fusion success based on biomechanical, histologic, and radiographic analyses. SUMMARY OF BACKGROUND DATA: The use of recombinant human bone morphogenetic proteins (rhBMPs) as osteoinductive bone graft substitutes or expanders has recently gained considerable research interest, particularly when applied in posterolateral arthrodesis. However, whether these results can be extrapolated to a successful interbody spinal arthrodesis remains uncertain. METHODS: Twelve sheep underwent a multilevel thoracic spinal decompression by thoracoscopic approach. Three noncontiguous destabilization sites (T5-T6, T7-T8, T9-T10) were prepared and randomly treated as follows. Control group treatments were nonsurgical, destabilization alone, and empty BAK. Experimental groups were treated with autograft alone, BAK device packed with autograft, or BAK device packed with rhOP-1. Four months after surgery, interbody fusion status was quantified by biomechanical testing, computed tomography, microradiography, and histomorphometry. RESULTS: Results of biomechanical analysis showed statistically higher segmental stiffness levels when comparing the control and experimental groups with four of the five testing methods (P < 0.05). Computed tomography and microradiography characterized destabilization alone as producing one fusion in six preparations; the empty BAK, two in six;, autograft alone, four in eight; BAK with autograft, five in eight; and BAK with rhOP-1 group, six in eight-all evidenced by woven trabecular bone spanning the fusion sites. Histomorphometry yielded significantly more trabecular bone formation at the fusion sites in the three experimental groups than in the two control groups (P < 0.05). CONCLUSIONS: Interbody spinal fusions showing biomechanical and histomorphometric equivalency to autologous fusions have been achieved with rhOP-1. The functional unit stability and histologic osteointegration evidenced by the BAK/rhOP-1 complex shows this interbody arthrodesis technique to be a viable alternative toconventional autologous iliac crest, thereby obviating the need for an iliac crest donor site and associated patient morbidity.     

脊柱后外侧融合过程中BMP-2、BMP-4基因的动态表达

目的：研究脊柱后外侧融合过程中骨形态发生蛋白(BMP)的表达情况，探讨BMP对融合过程的作用。方法：36只成年雄性新西兰白兔，制作L4、L5双侧横突间自体骨植骨模型，按术后处死时间(0d、2d、4d、1周、2周、3周、4周、5周、6周、10周、6个月、10个月)随机平均分为12组。将融合组织平均分为3等份，与横突交界的上、下区域定为边缘区，中间区域定为中央区。以RT-PCR法检测不同时间段、不同融合区域BMP-2 mRNA、BMP-4 mRNA的表达水平。结果：在脊柱融合术后1～6周，BMP-2和BMP-4表达量明显增高，并各自出现相应的峰值。中央区BMP表达水平的增幅及峰值明显低于边缘区，其开始增高的时间及峰值出现的时间滞后于边缘区1～3周，表现出明显的时间和空间差别：结论：脊柱融合中央区BMP低表达及时间滞后可能是不融合发生的重要原因。在融合早期补充外源性BMP可能有助于提高融合率。     

Osteogenic protein-1 overcomes the inhibitory effect of nicotine on posterolateral lumbar fusion

STUDY DESIGN: An established rabbit posterolateral lumbar fusion model was used to evaluate the ability of osteogenic protein-1 to overcome the inhibitory effect of nicotine. OBJECTIVE: To determine whether osteogenic protein-1 should be considered as a bone graft alternative for the patient who smokes. SUMMARY OF BACKGROUND DATA: Smoking interferes with the success of posterolateral lumbar fusion. This inhibitory effect has been attributed to nicotine and confirmed in a New Zealand white rabbit model. Osteoinductive protein-1 has been shown to induce posterolateral spine fusion reliably in the rabbit model. The effectiveness with which osteogenic protein-1 induces fusion in the presence of nicotine has not been studied previously. METHODS: Single-level posterolateral intertransverse process fusions were performed at L5-L6 in 18 New Zealand white rabbits. Either autograft or osteogenic protein-1 was used as grafting material. Nicotine was administered via subcutaneous mini-osmotic pumps. The animals were killed 5 weeks after surgery, and the resulting fusion masses were studied. RESULTS: Three rabbits (17%) were excluded because of complications. By manual palpation, two of the eight nicotine-exposed autograft rabbits (25%) and all of the nicotine-exposed osteogenic protein-1 rabbits (100%) were found to be fused. These results correlated well with those obtained from biomechanical testing. Histologically, the fusion zones of the nicotine-exposed autograft rabbits were distinctly less mature than the fusion masses of the nicotine-exposed osteogenic protein-1 rabbits. CONCLUSION: Osteoinductive protein-1 was able to overcome the inhibitory effects of nicotine in a rabbit posterolateral spine fusion model, and to induce bony fusion reliably at 5 weeks.     

Mesenchymal stem cell and gene therapies for spinal fusion

THE IDEAL GRAFT material to promote spinal fusion should possess osteoconductive, osteoinductive, and osteogenic properties. Although autogenous bone graft has all three qualities and is the standard for comparison, research has focused on finding alternatives that have similar efficacy but not the morbidities associated with graft donor sites. Efforts have focused on various osteoconductive scaffolds and introduction of osteoinductive proteins, including bone morphogenetic protein. Recently, interest in using osteoprogenitor cells, or osteogenesis, for spinal fusion has increased. Bone marrow aspiration allows the introduction of mesenchymal stem cells and ultimately osteoblasts to promote fusion. Preclinical studies suggest that the addition of osteoprogenitor cells to various osteoconductive materials results in a fusion rate similar to that of autograft. There is growing recognition that local gene therapy has the benefit of delivering therapeutic genes that encode novel osteoinductive proteins. Gene delivery offers an alternative to local implantation of recombinant protein, which typically requires high doses of the protein to result in a sufficient osteoinductive response. The findings of animal studies demonstrate that gene therapy results in sustained and regulated production of desired osteoinductive proteins and is efficacious in promoting spinal fusion; however, before treatment in humans can be undertaken, obstacles such as the safety profile, host immune response, transfection rates with insufficient transgene expression, and imprecise control of the timing of transgene expression must be overcome. In this review, the authors summarize the latest research efforts under way to promote spinal fusion with osteoprogenitor cells and gene therapy and discuss the clinical implications of these treatments.     

The effect of osteogenic protein-1 in instrumented and noninstrumented posterolateral fusion in rabbits.

BACKGROUND CONTEXT: The use of rigid instrumentation combined with bone graft makes intuitive sense given the requirements for vascular ingrowth, bone formation and a stable environment for the cellular events of healing to develop. However, with the advances of potent osteoinductive growth factors, the role of internal fixation may come into question. Whether bone morphogenic proteins (BMPs) would benefit from a more "stable" spinal segment for bone production and modeling remains unknown. In addition, it is unknown whether BMP and rigid fixation may have an additive effect on fusion healing. PURPOSE: This study is proposed to test the hypothesis that rigid fixation in the lumbar spine would be advantageous to achieve fusion for autogenous bone grafting, but fusion would occur regardless of fixation with the use of osteogenic protein (OP)-1. STUDY DESIGN/SETTING: A histologic and radiographic analysis of BMP in a rabbit lumbar fusion model. METHODS: Thirty-two rabbits were randomized into four groups: 1) control animals: in situ posterolateral L5-L6 arthrodesis using autogenous iliac crest bone graft; 2) fixation group: posterolateral arthrodesis L5-L6 with autogenous bone graft and interspinous fixation; 3) OP-1 group: in situ posterolateral L5-L6 arthrodesis using OP-1 and 4) combined OP-1 and fixation group. Radiographic fusion analysis was performed with computed tomography scans at 3 and 12 weeks after surgery. Decalcified histology was performed to assess tissue morphology and cellularity. RESULTS: Minimal evidence of fusion was noted at 3 weeks with autograft or OP-1. By 12 weeks, all OP-1-treated animals had solid fusion, whereas no fusion was noted in autograft animals. The addition of fixation slightly increased radiographic fusion at 3 weeks in autograft and OP-1 groups but did not affect OP-1 animals at 12 weeks where all were fused. Decalcified histologic results confirmed the proliferative bone formation noted with OP-1 and the variable cellular response with autograft. CONCLUSIONS: The results of the present study suggest that the osteoinductive effect of OP-1 may be only minimally enhanced early in the bone healing process but does not appear to be affected in the long term by spinal fixation in the rabbit intertransverse fusion model. Fixation appeared to enhance early fusion in the autograft group.     

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.     

Evaluation of carriers of bone morphogenetic protein for spinal fusion

STUDY DESIGN: Posterolateral lumbar transverse process fusion in a rabbit model was performed using two different carriers for recombinant human morphogenetic protein-2, one having a porous structure and the other being a Type I collagen sheet. OBJECTIVES: To compare the effectiveness of two different carriers for recombinant human morphogenetic protein-2 in achieving lumbar intertransverse process arthrodesis. SUMMARY OF BACKGROUND DATA: The application of osteoinductive growth factors at various anatomic sites, such as in long bones and spinal segments, has been performed experimentally by many researchers. Although many carriers of osteoinductive factors have been reported, the most effective carrier has not been established. We have reported the efficacy of sintered bovine bone, True Bone Ceramics, which is coated with Type I collagen as a carrier of recombinant human bone morphogenetic protein-2 in achieving lumbar intertransverse process arthrodesis. True Bone Ceramics is a crystallized form of bone minerals made from sintering bovine bone at high temperatures and possesses natural trabecular structure. The crystalline character of True Bone Ceramics is similar to that of artificial hydroxyapatite. In this study we focused on the structure of two different carriers to facilitate osteosynthesis in lumbar arthrodesis. METHODS: Fifty-four adult rabbits underwent bilateral lumbar intertransverse process arthrodesis at L4-L5. The animals were divided into five groups and had implants placed as follows: Group 1, autograft group, harvested autologous corticocancellous bone from the posterior iliac crest; Group 2, TBC group, True Bone Ceramics alone; Group 3, TBC-TBMP group, True Bone Ceramics coated with Type I collagen infiltrated with 100 microg of recombinant human bone morphogenetic protein-2; Group 4, collagen group, Type I collagen sheet; and Group 5, collagen-BMP group, implanted collagen sheet containing 100 microg of recombinant human bone morphogenetic protein-2. Spinal fusion was evaluated by radiographic analysis, manual palpation, biomechanical testing, and histologic examination at both 3 and 6 weeks after surgery. RESULTS: Radiographs in the TBC-TBMP group showed a continuous trabecular pattern within the intertransverse area at 3 weeks after surgery. The fusion mass in the intertransverse area was more prominent than in the other groups. At 3 weeks after surgery the TBC-TBMP group had higher fusion rates based on manual palpation, and the fusions showed significantly higher tensile strength and stiffness. The histologic findings in the TBC-TBMP group at 3 weeks after surgery showed a cortical bone rim around the edge of the fusion mass, and contiguous new bone appearing between the recipient bone and the matrix of TBC without evidence of foreign body formation. In the collagen-BMP group, less mature bone formation was present within the grafted area and the new bone was not contiguous, even at 6 weeks after surgery. CONCLUSIONS: As a carrier for recombinant human bone morphogenetic protein-2, True Bone Ceramics, possessing a bony or porous structure, was more effective than a Type I collagen sheet in achieving a faster and stronger lumbar spinal fusion in a rabbit model.     

Preclinical and clinical evaluation of osteogenic protein-1 (BMP-7) in bony sites.

Osteogenic proteins (OPs), also referred to as bone morphogenetic proteins (BMPs), are a family of bone-matrix polypeptides isolated from a variety of mammalian species. Implantation of osteogenic proteins induces a sequence of cellular events that leads to the formation of new bone. In preclinical studies, the implantation of recombinantly produced human osteogenic protein-1 (OP-1, also referred to as BMP-7) into surgically created, critical-size diaphyseal segmental defects resulted in the regeneration of new bone that was fully functional biologically and biomechanically. Injection of an OP-1 solution into a fresh fracture model accelerated the bone repair process compared with control fracture healing. This was the result of greater and earlier new bone formation. Further study has demonstrated that OP-1 can be used as a bone graft substitute to promote spinal fusion, aid in the incorporation of metal implants, and improve the performance of autograft and allograft bone. Clinical study of OP-1 implanted in conjunction with a bovine bone-derived type 1 collagen carrier for the treatment of tibial nonunion fractures has shown healing characteristics similar to that obtained with autogenous iliac crest bone graft. Advantages of OP-1 included no donor site complications, less blood loss, and a shorter operative time.     

Threaded cortical bone dowels in lumbosacral arthrodesis: a review

Lumbar fusion is a common spinal surgery, for which numerous devices have been developed to aid in segment stabilization. A threaded cortical bone dowel is a machined and processed bone allograft which is one such development. Threaded cortical bone dowels are attractive because of their osteoconductive nature and the opportunity to load them with osteogenic morselized bone autograft or osteoinductive growth factors, such as bone morphogenetic proteins. Although threaded cortical bone dowels have been in clinical use for more than 5 years, they have not been the subject of a comprehensive review. The current article covers the history, preparation, uses, safety, and efficacy of threaded cortical bone dowels in lumbosacral interbody fusion.     

Contemporary alternatives to synthetic bone grafts for spine surgery

The goal in performing spinal fusion techniques is to achieve solid fusion, which will maximize clinical outcomes. This goal has generated enormous interest in developing bone graft alternatives or extenders that enhance or replace autologous bone graft. Autogenous bone graft from the iliac crest is still the gold standard for graft materials because it has all 3 properties essential for adequate fusion. The search for a synthetic graft as good as or better than iliac crest bone graft has recently intensified with the emphasis on minimizing the invasiveness of surgical techniques, including harvest of iliac crest autograft (such harvesting can be associated with significant donor site morbidity). Increasingly being studied are biologically active substances intended to extend, enhance, or even replace autologous graft. These substances include (a) allograft cancellous chips and (b) cortical spacers that are both osteoconductive (provide bone scaffold) and weakly osteoinductive (promote new bone formation), including demineralized bone matrix products. Human recombinant bone morphogenetic proteins (BMPs), including recombinant human BMP-2 (rhBMP-2) and recombinant human osteogenic protein 1 (rhOP-1 or rhBMP-7), are being investigated in human clinical trials and show promise as autologous bone graft substitutes. Synthetic bone grafts (ceramics), such as hydroxyapatite and beta-tricalcium phosphate, provide scaffolds similar to those of autologous bone, are plentiful and inexpensive, and are not associated with donor morbidity. Furthermore, adding silicon may increase the bioactivity of calcium phosphate and enhance interactions at the graft-host interface.     

The efficacy of autologous laminectomy bone combined with bone graft extenders in posterolateral lumbar instrumented fusion

Iliac crest autograft has been used successfully for many years in spinal fusion operations. The main advantages to iliac crest autograft are the easy accessibility, the robust combination of osteogenic, osteoinductive, and osteoconductive properties, and the resultant efficacy. However, autograft iliac crest bone graft has fallen out of favor in spinal fusion operations due to the morbidity associated with harvest. Various bone graft substitutes have become commercially available that provide similar fusion rates when compared to iliac crest autograft. None of the bone graft substitutes can match iliac crest bone graft in all 3 osteogenic, osteoinductive, and osteoconductive parameters, but when combined with local autologous laminectomy bone and, therefore, used as a bone graft extender, may very well come close. This article reviews the main categories of bone graft substitutes and extenders and the role of these substances when combined with local autologous laminectomy bone in posterolateral lumbar instrumented fusion operations.     

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.     

Supplementation of autogenous bone graft with coralline hydroxyapatite in posterior spine fusion for idiopathic adolescent scoliosis

Twenty-seven consecutive patients with adolescent idiopathic scoliosis underwent posterior spinal fusion with pediatric Texas Scottish Rite Hospital instrumentation. Coralline hydroxyapatite (Interpore, Irvine, Calif) was mixed with limited autograft from posterior iliac crest (an approximate 70/30 ratio of coralline hydroxyapatite to autograft). Patient evaluation was based on clinical and radiographic findings. On initial radiographic evaluation, a "snowstorm" appearance consistent with the exoskeleton of the coralline hydroxyapatite was observed. After two years, the fusion mass had a "marble-like" appearance with distinct decreased visibility of the disk spaces in the fusion mass. This latter stage of "marbilization correlated with solid fusion clinically. All patients achieved solid fusion at an average follow-up of 27 months. Coralline hydroxyapatite is safe, biocompatible, and effective in augmenting autogenous bone graft in the treatment of idiopathic adolescent scoliosis with posterior spinal fusion. In addition to decreased donor site morbidity, this may be invaluable in cases where there is insufficient autograft available.     

重组人骨形态发生蛋白-2/异体骨复合骨用于兔腰椎融合的正电子发射计算机体层摄影-CT研究

目的 通过应用正电子发射计算机体层摄影-CT(PET-CT)研究重组人骨形态发生蛋白-2(rhBMP-2)/异体骨复合骨行兔腰椎融合术后不同时间点融合骨组织再血管化程度及成骨活性的变化.方法 成年雄性新西兰大白兔45只,随机分为3组,每组15只.在每只兔的L4、L5横突间行腰椎后路植骨融合术,3组分别植入rhBMP-2/异体骨复合骨条(复合骨组)、自体髂骨条(白体骨组)及异体髂骨条(异体骨组),每组于术后2、4、6周注射18F-NaF,利用PET-CT对各组动物进行全身显像,对比各组植骨区摄取值(SUV).结果 2、4、6周时复合骨组和白体骨组植骨区对18F-NaF的SUV均优于异体骨组,差异有统计学意义(P＜0.05);复合骨组植骨区的SUV在4、6周时高于自体骨组,差异有统计学意义(P＜0.05),2周时与自体骨组差异无统计学意义(P＞0.05).同一组内不同时间点复合骨组和白体骨组均在4、6周时局部SUV高于2周时,差异有统计学意义(P＜0.05);4周与6 周之间差异无统计学意义(P＞0.05).异体骨组的SUV 3个时间点问差异均无统计学意义(P＞0.05).结论 兔腰椎后路植骨融合术中PET-CT检测显示:rhBMP-2/异体骨复合骨可促进骨形成并改善局部血液供应,可作为替代自体骨的理想材料.     

The effect of osteogenic protein-1 dosing regimen on ectopic bone formation

Osteogenic protein-1 (also known as bone morphogenetic protein-7) is a member of the bone morphogenetic protein family. Several of the bone morphogenetic proteins, including osteogenic protein-1, have been shown to form bone at an ectopic site. However, optimal dosing regimens for the use of osteogenic protein-1 and other bone morphogenetic proteins in large bone defects have not been determined conclusively. We investigated the influence of osteogenic protein-1 (at doses of 0.1, 1, and 10 microg) with dosing regimens of single bolus, continuous infusion (alone), or bolus and continuous infusion in the rat ectopic subcutaneous bone formation assay (alkaline phosphatase units per microgram protein) in the presence of demineralized bone matrix. The biochemical results showed that the single bolus dosing regimen was significantly more effective than the continuous infusion alone and as effective as the bolus and continuous infusion regimens. The quality of the bone histologically confirmed the biochemical results. These data show that osteogenic protein-1 given as a single bolus is more effective in forming bone at an ectopic site than a continuous infusion of this protein.