rhBMP-2/异体骨复合骨应用于兔腰椎植骨融合的实验研究

目的评价rhBMP-2/异体骨复合骨在兔腰椎后路横突间植骨融合中的效果,探讨此复合骨替代自体骨用于腰椎后路横突间植骨融合的可能性。方法30只新西兰大白兔随机分为三组,行后路腰椎横突间植骨融合术,分别植入自体髂骨条、rhBMP-2/异体骨复合骨及单纯异体髂骨条。术后喂养6周,处死动物,取出标本,分别采取盲法进行手工测试,影像学、组织学观察及单向拉伸的生物力学测试,并用图像分析系统定量分析植骨区内成骨量,取得数据后进行综合评价。结果手工测试显示rhBMP-2/异体骨复合骨组融合率(90%)明显优于自体骨(40%)及异体骨组(20%)(P＜0．05)。影像学及组织学显示rhBMP-2/异体骨复合骨组成骨速度及骨成熟程度均优于其它两组。单向拉伸生物力学测试结果表明复合骨组和自体骨组两组间无明显差别(P＞0．05),但均明显优于异体骨组(P＜0．05)。定量分析显示植骨区内新骨形成面积复合骨组和自体骨组两组间无明显差别(P＞0．05),但均明显优于异体骨组(P＜0．05)。结论在兔腰椎后路横突间植骨融合术中,rhBMP-2/异体骨复合骨可促进骨形成并提高融合率,可作为替代自体骨的理想材料。     

Effect of Hydroxyapatite porous characteristics on healing outcomes in rabbit posterolateral spinal fusion model

Hydroxyapatite (HA) has been commonly used as a bone graft substitute in various kinds of clinical fields. To improve the healing capability of HA, many studies have been performed to reveal its optimal structural characteristics for better healing outcomes. In spinal reconstruction surgery, non-interconnected porous HAs have already been applied as a bone graft extender in order to avoid autogenous bone harvesting. However, there have been few experimental studies regarding the effects of the structural characteristics of HA in posterolateral lumbar intertransverse process spine fusion (PLF). The aims of this study were to investigate the effect of HA porous characteristics on healing outcomes in a rabbit PLF model in order to elucidate appropriate structural characteristics of HA as a bone graft extender. Thirty-six adult female Japanese White rabbits underwent bilateral intertransverse process fusion at the level of L5–6 without internal fixation. We prepared three types of HA with different porosities: HA with 15% porosity (HA15%), HA with 50% porosity (HA50%), and HA with 85% porosity (HA85%), all of which were clinically available materials. The HA15% and HA50% had few interconnecting pores, whereas the HA85%, which was a recently developed material, had abundant interconnecting pores. All rabbits were randomly divided into the following four groups according to the grafted materials: (1) HA15% + autogenous bone, (2) HA50% + autogenous bone, (3) HA85% + autogenous bone, (4) pure autogenous bone graft. The animals were euthanized at 5 weeks after surgery, and post-mortem analyses including biomechanical testing, radiographical and histological evaluations were performed. There was no statistically significant difference in either fusion rate and/or bending stiffness among the three HA groups. However, in histological and radiological analyses, both bone ingrowth rate and direct bone bonding rate in the HA85% group were significantly higher than those in the HA15% and HA50% groups, despite the similar value of bone volume rate in fusion mass among the three HA groups. In the HA85% group, bone ingrowth was achieved throughout the implanted HAs via interconnecting pores and there was excellent unification between the HA granules and the newly mineralized bone. On the other hand, in the non-interconnected porous HA groups, only a little bone ingrowth could be seen at the peripheral pores of the implanted HA, and its surface was mostly covered with fibrous tissue or empty space. The current study demonstrated that the HA porous characteristics had an effect on the histological outcomes in a rabbit PLF model. We would like to conclude that the interconnected high porous structure seems to be promising for the environment of PLF in the point of producing fusion mass with higher cellular viability. This is because the HA85% is superior in terms of integration with the newly formed bone in fusion mass compared to the non-interconnected porous HAs. However, the porous modifications of HA have little influence on fusion rate and mechanical strength because primary stabilization of the fusion segment is mainly achieved by bridging bone between the adjacent transverse processes outside the implanted materials, rather than the degree of integration between the newly formed bone and the HA granules in PLF.     

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。     

人工骨腰椎后外侧融合过程中BMP基因的表达

目的研究利用人工骨做脊柱后外侧融合时局部BMP的表达情况,探讨人工骨在此过程中是否具备骨诱导作用。方法选用36只健康成年雄性新西兰白兔,制作L4、L5双侧横突间植骨融合模型,一侧采用磷酸钙人工骨(CPC),另一侧采用自体骨作为对照。按术后动物不同处死时间(0、2、4d、1、2、3、4、5、6、10周、6、10个月)随机平分为12组。采用RTPCR法检测融合组织BMP2mRNA、BMP4mRNA的表达水平。结果CPC材料内部在融合的各个时间段均未检测到BMP2mRNA和BMP4mRNA的表达。与紧密结合的植骨床及融合交界面中BMP2mRNA和BMP4mRNA的表达水平随时间变化均没有明显的增高,与自体骨相比,CPC融合过程中不同时间段内BMP2mRNA、BMP4mRNA的表达水平均明显低于自体骨(P<0.05)。结论单纯利用CPC做脊柱融合时,局部缺乏BMP的有效表达,可能导致融合失败率的增加。     

Enhanced spinal fusion using a biodegradable porous mesh container in a rat posterolateral spinal fusion model

Background contextPosterolateral fusion (PLF) with an autogenous iliac bone graft is the most common procedure for treating various lumbar spinal diseases. However, the limited success and associated morbidity from an iliac crest graft demands new biologically competent graft enhancers or substitutes.PurposeTo investigate the feasibility of tubular mesh container made of bioabsorbable sutures (poly-1,4-dioxane-2-one, PDO) for spinal fusion.Study designExperimental animal study.MethodsA biodegradable PDO tubular mesh container was used to contain small pieces of bone grafts. Twenty Sprague-Dawley male rats underwent PLF between L4 and L5 transverse processes with bilateral iliac grafts. Experimental animals were assigned into two different groups: autograft-only group (N=10) that underwent PLF with autograft-only or mesh container group (N=10) that underwent PLF with tubular mesh container filled with autogenous bone grafts. The rats were sacrificed at 8 weeks postoperatively, and the lumbar spines were removed. Spinal fusion was evaluated by manual palpation, microcomputed tomography, three-point bending test, and histological examination.ResultsSolid fusion was achieved in all cases of the mesh container group, whereas the autograft-only group showed 60% of solid fusion. New bone mass was higher and more solidly fused in the mesh container group than the autograft-only group (p<.01). Volume of fusion mass and density of bone were significantly higher in the mesh container group (p<.05). In all cases, inflammatory response was minimal.ConclusionsThis study demonstrated that a tubular mesh container made of bioabsorbable suture is useful to hold small pieces of bone grafts and to enhance spinal fusion.     

Pharmacophysiology of bone and spinal fusion

Background context

In recent years, the number of complex spinal surgeries has increased significantly in the elderly population, where the prevalence of low bone density is highest. Consequently, spine surgeons often treat osteoporotic patients who are associated with higher rates of instrumentation failure. Therefore, establishing a successful fusion requires an appropriate substrate for bone formation and local bone remodeling. The fusion process can be supported by therapies that seek to shift the balance of bone homeostasis to increased formation and reduced resorption.

Purpose

Thorough understanding of the physiology of bone formation and adjunctive therapies can help improve fusion rates. Therefore, we present a thorough review of the latest pharmacologic agents used to enhance bone strength and surgical spinal fusion.

Methods

Systematic review of literature.

Results

Current knowledge on bone physiology has led to the development of several pharmacologic agents that enhance bone formation and strengthen the human skeleton. At present, natural supplements of vitamin D and calcium or synthetic medications like bisphosphonates are widely used before and after spine surgeries to enhance bone fusion. Additional physiologic agents, including testosterone, parathyroid hormone, calcitonin, and growth hormone, have been shown to improve bone mass density or spinal fusion in both animal and human studies. As in other medical fields, gene therapy has shown viability and promise with the use of both viral and nonviral vectors.

Conclusions

Through the understanding of bone physiology, numerous natural and synthetic pharmacologic agents have been developed to enhance the body's skeleton and to improve outcomes of spinal fusion surgery.     

Biomechanical evaluation of the New Zealand white rabbit lumbar spine: a physiologic characterization

Physiologic motions of the human, sheep, and calf lumbar spines have been well characterized. The size, cost, and ease of care all make the rabbit an attractive alternative choice for an animal lumbar spine model. However, comparisons of normal biomechanical characteristics of the rabbit lumbar spine have not been made to the spines of larger species. The purpose of this study was to establish baseline physiologic kinematic data for the rabbit lumbar spine. Ten skeletally mature New Zealand white rabbit osteoligamentous spines were obtained. L4-L7 spine segments were harvested and mounted. Multi-directional flexibility testing was performed by applying pure moments up to 0.27 Nm. Resulting rotations were measured using an Optotrak system. Data were analyzed for each intervertebral level in the three planes of rotation. The three levels tested had roughly similar range of motion (ROM). The mean (SD) angular ROMs in flexion for L4-L5, L5-L6, L6-L7 were 12.10° (2.59°), 12.38° (2.70°), and 15.17° (3.22°), respectively. The ROMs in extension were 5.86° (1.21°), 5.58° (1.48°), and 6.13° (2.03°). Lateral bending and axial rotation were roughly symmetric due to the symmetric nature of the spine. For right lateral bending, the ROMs were 8.25° (2.44°), 4.96° (1.70°), and 4.25° (1.20°). For left axial rotation, the ROMs were 1.23° (1.16°), 0.35° (0.61°), 0.87° (0.64°). Neutral zone (NZ) was on average 60% (29%) of ROM for the motions studied. The physiologic ROM of the New Zealand white rabbit lumbar spine was found to be similar between the rabbit and human. This relatively conserved physiologic flexibility supports the use of the rabbit as a model of the lumbar spine for kinematic studies. However, the overall NZ was found to be a greater percentage of ROM in the rabbit than the corresponding percentage in the human (60% as compared to 25%). This suggested that the rabbit lumbar spine has a greater laxity than that of the human. Received: 23 August 1999 Revised: 15 December 1999 Accepted: 26 January 2000     

动力内固定融合术对失稳脊柱稳定作用的实验研究

目的：探讨动力椎弓根螺钉内固定的优越性。方法：18只山羊随机分为3组，正常对照组（A组，仅作脊柱后路皮肤切开，L2～L4节段椎旁肌剥离）、动力固定融合组（B组，在A组基础上切除L3后部结构后行动力固定融合）和坚强同定融合组（C组，同B组但改为坚强固定融合）。术后24周处死动物，截取L1-L6节段脊柱标本，在脊柱三维运动试验机上测试固定节段运动范围，然后在MTS 858试验机上进行压缩刚度测试。A组标本测试完后切除L3后部结构作为损伤组（D组）重复稳定性和刚度测试，B组和C组取出内固定器后重复刚度测试。结果：与D组相比．B组和C组屈伸、侧弯和轴向旋转活动范围明显减少（P〈0．01），而且在屈伸、侧弯方向上比A组更稳定。与D组相比，B组和C组刚度均显著性提高（P〈0.01）；B组和C组内固定器取出后与取出前刚度之比的均值分别为85．51％、74．49％，有显著性差异（P〈0．05）。结论：动力内固定和坚强内固定融合均能恢复山羊失稳脊柱的稳定性，但动力内同定能增加载荷分享。     

Allograft alone versus allograft with bone marrow concentrate for the healing of the instrumented posterolateral lumbar fusion

Background contextSpondylodesis in the operative management of lumbar spine diseases has been the subject of numerous studies over several decades. The posterolateral fusion (PLF) with pedicle screw fixation is a commonly used procedure.PurposeTo determine whether the addition of bone marrow concentrate (BMC) to allograft bone increases fusion rate after instrumented posterior lumbar fusion.Study designThe study was prospective, randomized, controlled, and blinded.MethodsEighty patients with degenerative disease of the lumbar spine underwent instrumented lumbar or lumbosacral PLF (22 men, 58 women; body mass index less than 35 for a good visualization of the PLF in the X-rays). In 40 cases, the PLF was done with spongious allograft chips alone (Group I, age 62.7 years in average, range 47–77 years, level of fusion 1–2). In another 40 cases, spongious allograft chips were mixed with BMC (Group II, age 58.5 years in average, range 42–80, level of fusion 1–3), including the mesenchymal stem cells (MSCs). Patients were scheduled for anteroposterior and lateral radiographs 12 and 24 months after the surgery and for computed tomography scanning 24 months after the surgery. Fusion status and the degree of mineralization of the fusion mass were evaluated separately by two radiologists blinded to patient group affiliation. The bony mass was judged as fused if there was uninterrupted bridging of well-mineralized bone between the transverse processes or sacrum, with trabeculation indicating bone maturation on least at one side of the spines.ResultsIn Group I at 12 months, the bone graft mass was assessed in X-rays as fused in no cases (0%) and at 24 months in four cases (10%). In Group II, 6 cases (15%) achieved fusion at 12 months and 14 cases (35%) at 24 months. The statistically significant difference between both groups was proven for complete fusion at both 12 (p=.041) and 24 months (p=.011). Computed tomography scans showed that 16 cases (40%) in Group I and 32 cases (80%) in Group II had evidence of at least unilateral continuous bridging bone between neighboring vertebrae at 24 months (p<.05).ConclusionsWe have confirmed the hypothesis that the autologous BMC together with the allograft is a better alternative for PLF than the allograft alone. The use of autologous MSCs in form of BMC in combination with allograft is an effective option to enhance the PLF healing.     

脊柱手术切口延迟愈合

目的：分析脊柱手术切口延迟愈合的原因，探讨促进愈合的方法。方法：依据我院1988年6月至2002年12月42例脊柱手术切口不愈合的临床资料，对延迟愈合的原因、表现及处理方法进行了分类及讨论。结果：9例结核患者再次手术后6例愈合，1例窦道形成，2例死亡；切口裂开2例中1例经切口再缝合愈合良好，另1例经10个月长期换药切口愈合；7例切口感染者均在1个月内控制感染；9例脑脊液漏，其中8例经保守治疗愈合，1例行脑脊膜再次修补术；1例硬膜外血肿清除后愈合良好；霉菌感染2例，其中1例经病灶清除后切口愈合，另1例演变成复发性窦道炎；4例压疮去除压迫后溃疡愈合；另外8例切口延迟愈合者中止血水引起者4例，脂肪液化2例，皮肤过敏2例，均经红外线照射后切口愈合。结论：脊柱手术切口延迟愈合的主要因素为医源性，大部分切口延迟愈合可以通过保守治疗治愈，存在3个月以上的窦道或溃疡需手术处理去除影响愈合的因素。     

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.     

Effect of a single dose of pamidronate administered at the time of surgery in a rabbit posterolateral spinal fusion model

Spinal fusion is usually performed on patients who receive bisphosphonates (BP); however, limited data on their action on spinal fusion are available. Previous studies in animal models have shown that chronic administrations of BP reduced spinal fusion rates, and only one study has shown that a single dose administration of zolendronic acid increased fusion rate. The objective of the present study was to evaluate if pamidronate (PA), which was previously demonstrated to reduce spinal fusion rate when administered continuously for 8 weeks, would increase the spinal fusion rate if administered in a single dose at the time of surgery in a rabbit model. Thirty-two New Zealand rabbits underwent an L5–L6 posterolateral intertransverse fusion with iliac crest autograft. Animals were randomized to receive either PA 3 mg/kg in a single dose immediately after surgery, or normal saline. Animals were killed 8 weeks after surgery and fusion was determined by manual palpation and radiographic analysis. Fusion healing was obtained in eight rabbits (50%) in the PA group and in four animals (25%) in the control group, p = 0.137. In a rabbit model, a single dose of PA did not decrease lumbar spinal arthrodesis consolidation rates, but it obtained a nonsignificant higher spinal fusion rate.     

Factors influencing arthrodesis rates in a rabbit posterolateral spine model with iliac crest autograft

Purpose

The rabbit posterolateral intertransverse spine arthrodesis model has been widely used to evaluate spinal biologics. However, to date, the validity and reproducibility of performance of iliac crest bone graft, the most common and critical control group, has not been firmly established. We evaluated original research publications that utilized this model, identified which experimental conditions affected fusion rates, and developed an algorithm to predict fusion rates for future study designs.

Methods

A MEDLINE search was performed for publications through December, 2011 that utilized this model to evaluate fusion rates elicited by iliac crest autograft. All study parameters were recorded, and logistic regression analyses were performed to determine the effects of these variables on fusion rates as determined by either manual palpation or radiographs.

Results

Seventy studies with 959 rabbits in 102 groups met the inclusion criteria. Excluding studies that measured fusion at 4 or fewer weeks or intentionally tried to decrease the fusion rate, the overall fusion rate for autograft was 58.3 ± 16.3 % (mean ± SD) as determined by manual palpation and 66.4 ± 17.8 % by plain radiographs. Regression analysis demonstrated a difference between these outcome measures with a trend towards significance (p = 0.09). Longer time points and larger volumes of autograft resulted in significantly greater reported fusion rates (p < 0.0001 and p < 0.05, respectively). Neither strain, age, weight, nor vertebral level significantly affected fusion rates.

Conclusions

Although experimental conditions varied across studies, time point evaluation and autograft volume significantly affected fusion rates. Despite some variability demonstrated across certain studies, we demonstrated that when the time point and volume of autograft were controlled for, the iliac crest control group of the rabbit posterolateral spinal arthrodesis model is both reliable and predictably affected by different experimental conditions.     

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.     

Erythropoietin augments bone formation in a rabbit posterolateral spinal fusion model

We tested the hypothesis that erythropoietin (EPO) enhances bone formation after posterolateral spinal fusion (PLF) in a rabbit model. Thirty-four adult rabbits underwent posterolateral intertransverse arthrodesis at the L5-L6 level using 2.0 g autograft per side. The animals were randomly divided into two groups receiving subcutaneous daily injections of either EPO or saline for 20 days. Treatment commenced 2 days preoperatively. Hemoglobin was monitored at baseline and 2, 4, and 6 weeks after fusion surgery. After euthanasia 6 weeks postoperatively, manual palpation, radiographic, and histomorphometric examinations were performed. Bone volume of the fusion mass was estimated by CT after 6 weeks. EPO increased bone fusion volume to 3.85 ccm (3.66-4.05) compared with 3.26 ccm (2.97-3.55) in the control group (p<0.01). EPO treatment improved vascularization of the fusion mass and increased hemoglobin levels (p<0.01). Fusion rate tended to be higher in the EPO group based on manual palpation, CT, and radiographic examinations. For the first time EPO has shown to augment bone formation after autograft PLF in a rabbit model. Increased vascularization provides a partial explanation for the efficacy of EPO as a bone autograft enhancer.     

Platelet-rich plasma enhances bone union in posterolateral lumbar fusion: A prospective randomized controlled trial

Background Context

Platelet-rich plasma (PRP) accelerates bone union in vivo in a rodent model of spinal fusion surgery. However, PRP's effect on bone union after spinal surgery remains unclear.

The effect of noggin interference in a rabbit posterolateral spinal fusion model

Study design

Noggin protein levels and spinal fusion rates were compared in a rabbit model after application of siRNA against BMP antagonist noggin in paraspinal muscle.

Objective

To test whether endogenous BMPs are sufficient to form bone in the absence of their antagonists, using noggin siRNA to interrupt the negative feedback loop on endogenous BMP within the paraspinal muscles in rabbits.

Summary of background data

Unused Posterolateral lumbar fusion is a standard surgical treatment for many spinal disorders, yet even under ideal conditions the rate of non-fusion approaches 25 %. BMPs are effective in promoting bone formation, and are inhibited by antagonists such as noggin. We have previously shown that in this model, endogenous BMPs are present and endogenous BMP antagonist noggin is strongly increased during spinal fusion. Previous studies have found that noggin siRNA enhanced spinal fusion in combination with supra-physiological amounts of exogenous BMP; however, the effect of the siRNA alone remains unknown.

Methods

A posterolateral intertransverse rabbit lumbar fusion was utilized, as established by Boden et al. SiRNA against noggin was electroporated into paraspinal muscle to determine its effect on fusion. Outcome measures included noggin protein expression, and assessment of spinal fusion at 6 weeks.

Results

SiRNAs were effective in reducing overexpressed noggin in vitro. Noggin protein was successfully knocked down in vivo for the initial 7 days in our rabbit model and returned to detectable levels by 4 weeks and to normal levels by 6 weeks. The overall fusion rate was not significantly enhanced compared to established controls from our earlier work (Tang et al.).

Conclusions

Early noggin suppression does not appear to enhance the BMP activity sufficiently to significantly affect final fusion rates in our model.     

Lumbar posterolateral fusion using heparin-conjugated fibrin for sustained delivery of bone morphogenic protein-2 in a rabbit model

We had devised a heparin-conjugated fibrin (HCF) system to deliver bone morphogenic proteins (BMPs) for a long-term period to enhance bone regeneration. In the present study, we tested the effectiveness of the delivery system for spinal fusion in a rabbit model. A total of 15 rabbits underwent posterolateral lumbar spine fusion with BMP-2 (50 μg per collagen sponge). The control group received only collagen sponges without BMP-2, another group (short-term delivery [SD] group) received collagen sponges filled with fibrin gel loaded with BMP-2, and the third group (long-term delivery [LD] group) received collagen sponges filled with HCF loaded with BMP-2. All animals were euthanized 8 weeks after surgery, and the fusion was assessed by radiographs, manual palpation, computed tomography, and mechanical testing. The fusion rate was significantly higher in the LD group using HCF than in the SD group or in the control group. Biomechanical testing showed the tensile strength was also significantly higher in the LD group using HCF than in other groups. The HCF system can provide a good option for the delivery of BMP-2 on posterolateral lumbar spine fusion.     

兔脊柱VX2移植瘤模型的建立及生物学特性观察

目的探讨兔脊柱VX2移植瘤模型的建立方法及其生物学特性。方法新西兰大白兔25只,分为两组。实验组（20只）采用VX2瘤细胞悬液经横突椎弓根注射法建立兔脊柱VX2移植瘤动物模型,对照组（5只）以生理盐水注射代替VX2瘤细胞悬液进行同样操作。接种后每天观察下肢神经功能变化,接种术后第2周起每周行X线、CT影像学检查肿瘤生长情况。动物出现下肢瘫痪、死亡或接种后6周为观察终点,取出接种椎作组织学检查。结果对照组5只兔观察期内均未出现神经功能障碍,检查未见异常。实验组中1只兔因钻孔破人椎管,退出实验。19只兔成功接种,1只于接种术后9天感染死亡,1只经病理检查证实观察截止时仍无肿瘤生长,其余17只成瘤（89．5％）。观察期内9只出现完全瘫痪,5只不全瘫,其余3只未出现神经功能障碍。结论经横突-椎弓根种植法建立兔脊柱VX2移植瘤模型具有成瘤率高、可重复性好的特点。该模型能较好地模拟脊柱转移癌发展、压迫脊髓导致瘫痪的病理过程,有助于脊拄转移癌各种治疗模式的研究和探索。     

The effect of ketoprophen on lumbar spinal fusion healing in a rabbit model. Laboratory investigation

OBJECT: Several reports have shown that nonsteroidal antiinflammatory drugs (NSAIDs) have an inhibitory effect in osteogenesis and reduce heterotopic ossification in humans. A deleterious effect of NSAIDs in posterolateral intertransverse process fusion has also been suggested. The authors used a validated rabbit model to try to determine the influence of the NSAID ketoprophen on the fusion rate in lumbar spinal arthrodesis. METHODS: Thirty New Zealand male rabbits underwent posterolateral (intertransverse process) bilateral spinal fusions at a single level, using autologous bone graft obtained from both iliac crests. The animals were randomized after the operation, so that 15 rabbits received ketoprophen as a postoperative analgesic and the other 15 received the postoperative analgesic tramadol. The animals were killed 8 weeks after surgery, and fusion status was determined by inspection, palpation, anteroposterior radiographs, and histological analysis. RESULTS: A solid fusion was obtained in eight rabbits (53%), and pseudarthrosis in seven rabbits (47%) in each group. CONCLUSIONS: These findings suggest that the use of ketoprophen after intertransverse spinal fusion at a single level does not decrease the fusion rate, compared with tramadol.