Bone morphogenetic protein-2 compared to autologous iliac crest bone graft in the treatment of long bone nonunion

This retrospective study investigated the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) mixed with cancellous allograft on fracture healing compared to iliac crest autograft in the treatment of long bone nonunion. Eighty-nine patients with 93 established long bone nonunions treated between January 2002 and June 2004 at a single academic Level I trauma center were evaluated. Patients with clinical and radiographic evidence of failed fracture union underwent nonunion debridement, revision of fixation, and implantation at the nonunion site of either rhBMP-2 or the standard treatment autologous iliac crest bone graft. Union rate, operative time, estimated intraoperative blood loss, hospital length of stay, and postoperative infections were recorded. Nineteen nonunions received rhBMP-2 on a specialized carrier matrix (an absorbable collagen sponge) mixed with cancellous allograft, and 74 nonunions were treated with autologous iliac crest bone graft. There was no statistical difference in the rate of healing between treatment groups (68.4% vs 85.1%, respectively; P=.09). Incidence of postoperative infection was 16.2% after autologous iliac crest bone graft and 5.3% after rhBMP-2/absorbable collagen sponge (P=.22). Iliac crest autograft was associated with longer operative procedures (257.9±93.0 vs 168.9±86.5 minutes; P=.0007) and greater intraoperative blood loss (554.6±447.8 vs 331.6±357.2 mL; P=.01). These outcomes suggest that rhBMP-2 may provide a suitable alternative to autologous iliac bone graft, with the possible advantages of shorter operative time and reduced intraoperative blood loss, and may be considered as part of the orthopedic surgeon's treatment options.     

外源性重组人骨形态发生蛋白-2应用于兔腰椎植骨融合中细胞增殖的实验研究

目的 探讨外源性重组人骨形态发生蛋白-2(rhBMP-2)应用于兔腰椎后路横突植骨融合中的促成骨效应细胞增殖作用及其成骨机制. 方法 45只新西兰大白兔随机分为三组(n=15),建立腰椎后路横突间植骨融合模型,分别植入rhBMP-2/异体骨复合骨条(复合骨组)、自体髂骨条(自体骨组)、单纯异体髂骨条(异体骨组).用流式细胞仪检测2、7、14、28、35 d具有成骨效应的骨髓基质细胞(MSCs)、成骨细胞、血管内皮细胞的增殖量. 结果复合骨组MSCs增殖量在术后2、7、35 d均比自体骨组和异体骨组高,差异均有统计学意义(P<0.05).复合骨组成骨细胞增殖量除在术后2 d高于自体骨组,差异有统计学意义(P=0.028)外,在其他时间点差异均无统计学意义(P>0.05),但复合骨组成骨细胞增殖量在术后2、7、14、28、35 d时均高于异体骨组,差异有统计学意义(P<0.05).复合骨组血管内皮细胞增殖量在术后2、7、28 d均高于自体骨组和异体骨组,差异有统计学意义(P<0.05).结论 在脊柱融合的不同时间段,外源性rhBMP-2能有效地促进MSCs、成骨细胞、血管内皮细胞增殖.     

Recombinant human bone morphogenetic protein-2: a novel osteoinductive alternative to autogenous bone graft?

Autogenous bone grafts from the iliac crest have long been the gold standard for repair and reconstruction of bone; however harvesting of the grafts from the iliac crest is associated with donor site morbidity, particularly chronic pain. The bone morphogenetic proteins (BMPs) are soluble bone matrix glycoproteins that induce the differentiation of osteoprogenitor cells into osteogenic cells and have the potential to act as autogenous bone graft substitutes. BMP-2, which can be produced with recombinant technology, is highly osteoinductive, inducing bone formation by stimulating the differentiation of mesenchymal cells into chrondroblasts and osteoblasts. At present, more than 1,000 patients have received rhBMP-2 in clinical trials for acute open tibial fracture and interbody fusion procedures for the treatment of degenerative disc disease. Data suggest that rhBMP-2 therapy may offer an effective alternative to autogenous bone graft for recalcitrant bone unions and spinal fusion, obviating donor site morbidity.     

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.     

Recombinant human bone morphogenetic protein-2 enhances anterior spinal fusion in a thoracoscopically instrumented animal model

BACKGROUND: Thoracoscopically assisted anterior spinal arthrodesis and instrumentation is being used more widely to treat idiopathic scoliosis. However, harvesting autologous bone increases operative time and morbidity. The purpose of this study was to compare autologous iliac crest and rib graft with recombinant human bone morphogenetic protein-2 (rhBMP-2) in thoracoscopically assisted anterior spinal arthrodesis and instrumentation in an animal model. METHODS: Twenty-two pigs underwent thoracoscopically assisted anterior spinal arthrodesis. Each animal had five contiguous thoracic discectomies followed by anterior instrumentation. The animals were randomly assigned to five treatment groups. Group I consisted of control animals that received no graft material; group II, animals treated with autologous rib graft; group III, animals treated with autologous iliac crest graft; group IV, animals treated with an rhBMP-2-composite sponge (collagen-hydroxyapatite-tricalcium phosphate carrier); and group V, animals treated with a composite sponge carrier alone. The animals were killed four months after the procedure, and the spines were harvested. The fusion mass was assessed with use of axial and sagittal computed tomography scans. The spines were tested biomechanically with incremental loads applied in the frontal and axial planes to achieve bending moments of up to 6.0 N-m. Angular motion at each segment was recorded with use of a three-dimensional motion analysis system. Histomorphometric analysis of each undecalcified disc segment was also performed. RESULTS: The fusion grades, according to computed tomography analysis with use of a 4-point grading system in which scores of 3 and 4 indicated a solid fusion, were 0.6 point for group I, 2.1 points for group II, 2.3 points for group III, 3.8 points for group IV, and 0.4 point for group V. Group IV (the rhBMP-2-treated animals) had a higher grade than all of the other groups. Group II (rib graft) and group III (iliac crest) had similar grades, and both were greater than group I (the untreated controls) and group V (composite sponge alone) (p < 0.05). In axial rotation, lateral bending, and flexion-extension, the spines in group IV were stiffer than those in the four other groups (p < 0.05); the spines in groups II and III were similar, and the spines in both of those groups were stiffer than those in groups I and V (the control groups). Histologic analysis demonstrated that the total new-bone area, expressed as a percentage of the total disc space area, was 23.2% in group I, 37.1% in group II, 37.2% in group III, 48.5% in group IV, and 5.9% in group V. Group IV had significantly greater bone formation than all of the other groups (p < 0.001). The animals treated with rib graft (group II) and iliac crest (group III) had a similar amount of bone formation, and it was greater than that in both control groups (p < 0.001). CONCLUSIONS: The rhBMP-2 significantly increased the prevalence and quality of the spinal fusion after thoracoscopically assisted anterior arthrodesis and instrumentation in an animal model compared with that in the other treatment groups and in the controls.     

Posterolateral lumbar intertransverse process spine arthrodesis with recombinant human bone morphogenetic protein 2/hydroxyapatite-tricalcium phosphate after laminectomy in the nonhuman primate.

STUDY DESIGN: A nonhuman primate lumbar intertransverse process arthrodesis model was used to evaluate recombinant human bone morphogenetic protein 2 (rhBMP-2) in a hydroxyapatite-tricalcium phosphate (HA-TCP) carrier as a complete bone graft substitute. OBJECTIVES: To assess the ability of a ceramic material to serve as a carrier for various doses of rhBMP-2 as a bone graft substitute in a primate model of posterolateral intertransverse process spinal fusion after laminectomy. SUMMARY OF BACKGROUND DATA: The reported non-union rates for posterolateral lumbar spine fusion with autogenous iliac crest bone range from 5-35%. Recombinant human bone morphogenetic protein 2 has shown potential to serve as a bone graft substitute for posterolateral intertransverse process spine fusion. Although a resorbable collagen sponge was a suitable carrier in rabbits and dogs, it was too compressible for the paraspinal muscles in rhesus monkeys. This failure of the collagen carrier has prompted evaluation of the feasibility of an alternative carrier material and the required dose of rhBMP-2. METHODS: Twenty-one adult rhesus monkeys underwent a laminectomy at L4-L5 followed by bilateral intertransverse process arthrodesis via the same midline incision (n = 16) or a minimally invasive video-assisted posterolateral approach (n = 5). Bone graft implants on each side consisted of either 5 cm3 of autogenous iliac crest bone or 60:40 HA-TCP blocks (1.2 x 0.5 x 3.7 cm) loaded with a solution containing 0, 6, 9, or 12 mg of rhBMP-2 per side. The monkeys were killed 24 weeks after surgery. Inspection, manual palpation, radiography, and histology were used to assess fusion and to detect any bony growth into the laminectomy defect. RESULTS: Fusion was not achieved in any of the monkeys treated with autogenous iliac crest bone graft. Both of the monkeys treated with the HA-TCP blocks with 0 mg rhBMP-2 achieved fusion. All 15 monkeys treated with the HA-TCP blocks and either of the three doses of rhBMP-2 achieved solid fusion. Two animals had extension of the fusion on one side because of malpositioned ceramic block. The results in animals fused via the minimally invasive video-assisted technique were the same as inthose fused with the open technique. Histologic analysis showed some ingrowth of bone into the ends but not-through the ceramic block in the absence of rhBMP-2. When the ceramic blocks were loaded with rhBMP-2 there was a dose-dependent increase in the amount and quality of bone throughout the ceramic carrier based on qualitative assessment. No significant bone encroachment on the exposed thecal sac through the laminectomy defect was observed in any of the monkeys. CONCLUSION: Hydroxyapatite-tricalcium phosphate proved to be a suitable carrier for rhBMP-2 in the posterolateral spine fusion model in rhesus monkeys. Even in the presence of a laminectomy defect, there was no evidence of bone induction outside the confines of the ceramic carrier.     

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.     

In vivo evaluation of coralline hydroxyapatite and direct current electrical stimulation in lumbar spinal fusion.

STUDY DESIGN: An animal model of posterolateral intertransverse process lumbar spinal fusion using autologous bone, coralline hydroxyapatite, and/or direct current electrical stimulation. OBJECTIVES: To evaluate the effect of an osteoconductive bone graft substitute and direct-current electrical stimulation on the rate of pseudarthrosis in a rabbit spinal fusion model. SUMMARY OF BACKGROUND DATA: Conventional techniques for the surgical treatment of degenerative conditions in the lumbar spine have a substantial failure rate and associated morbidity. Bone graft substitutes and electrical stimulation are alternative techniques to enhance fusion rates and limit the morbidity associated with posterolateral intertransverse process fusion using autologous iliac crest bone graft. METHODS: Fifty-three adult female New Zealand White rabbits underwent single-level lumbar posterolateral intertransverse process fusion. Animals were assigned to one of four groups using either autologous bone (Group I), coralline hydroxyapatite with autologous bone marrow aspirate (Group II), coralline hydroxyapatite with a 40-microA implantable direct current electrical stimulator and bone marrow aspirate (Group III), or coralline hydroxyapatite with a 100-microA implantable direct current electrical stimulator and bone marrow aspirate (Group IV). Animals were killed at 8 weeks, and fused motion segments were subjected to manual palpation, mechanical testing, and radiographic and histologic analysis to assess the fusion mass. RESULTS: Successful fusion was achieved in 57% (8/14) of animals in Group I, 25% (3/12) in Group II, 50% (6/12) in Group III, and 87% (13/15) in Group IV. Mean stiffness and ultimate load to failure were significantly higher in Group IV than in all other groups (P < 0.05). Histologic analysis demonstrated a qualitative increase in fusion mass in Group IV versus all other groups. CONCLUSIONS: Direct-current electrical stimulation increased fusion rates in a dose-dependent manner in a rabbit spinal fusion model. Coralline hydroxyapatite is an osteoconductive bone graft substitute, and thus requires an osteoinductive stimulus to ensure reliable fusion rates. Furthermore, coralline hydroxyapatite and direct current electrical stimulation can be used together to increase fusion rates in a rabbit spinal fusion model while avoiding the morbidity associated with harvesting iliac crest bone.     

Bone union rate with recombinant human bone morphogenic protein-2 versus autologous iliac bone in PEEK cages for anterior lumbar interbody fusion

Purpose

Autologous iliac crest bone graft (ICBG) is the gold standard material for spinal fusion. Bone graft substitutes, such as recombinant human bone morphogenic protein 2 (rhBMP-2) have been developed to promote spinal fusion and address morbidity issues related to ICBG harvesting. The objective of this study was to compare bone fusion rates after anterior lumbar interbody fusion (ALIF) between ICBG and rhBMP-2 by examining thin-cut computed tomography (CT) images at the one year follow-up.

Methods

Fifty one patients (62 levels) who underwent single- or two-level ALIF via the video-assisted minimally invasive anterior approach in our institution were assessed. Radiolucent cages were inserted in all cases. Each cage has a middle beam delimiting two chambers. Grafting was performed as follows: one chamber was filled with autologous ICBG, and the other chamber was filled with 6 mg of rhBMP-2. Thin-cut CT-scan multiplanar reconstruction analyses were performed to assess the rate and quality of bone fusion at one year of follow-up.

Results

Fusion was observed in 55 levels (88.7 %), with significant differences in fusion rates with rhBMP-2 and ICBG (71 % vs. 88.7 %) (P=0.001). Osteogenesis in the rhBMP-2 chamber had a centripetal pattern in all cases, leaving a central void in 97.7 % of cases representing 38.3 % of the surface of its chamber (range 0–80.3 %). In ICBG chambers, graft resorption was present in 44.4 %, representing 9.8 % of the chamber surface (range 0–52.2 %).

Conclusion

RhBMP-2 was inferior to ICBG in terms of rate and quality of bone fusion in one- or two-level ALIF.     

Minimally invasive bone harvesting tools

The most readily available source for autologous bone graft used in spinal fusion (the gold standard) is the iliac crest. However, the open surgical approach for harvesting corticocancellous iliac bone is associated with a marked increase in morbidity. This study suggests two alternatives to the traditional open harvesting procedure. For anterior interbody fusion procedures using a cage, the autologous bone is harvested regionally from a neighboring vertebral body. Alternatively, using minimally invasive techniques, a custom bone graft harvester with a flexible tube and cutting tip allows harvesting of autologous bone from ¶a single entry point at the iliac crest. The effect on the mechanical strength of a lumbar vertebra of removing a cylindrical regional bone graft was studied in a cadaveric model. The bone defect was filled using three different filler materials: a porous tricalcium phosphate plug, a porous tantalum plug, and a self-setting calcium phosphate cement. After plug removal, the vertebral body's strength in flexion/compression loading was reduced significantly, but could be restored to at least intact values with any of the three filler materials. The minimally invasive bone graft harvester was tested in three cadaveric pelves. With the cutting tip being guided within the cortical boundaries of the pelvis, cancellous bone volumes of 10-20 cc could be harvested from each iliac bone. Regional bone graft harvest in anterior spine surgery is suggested to be anatomically safe and biomechanically acceptable. Any of the three filler materials can restore the vertebral body's mechanical strength, but the filler's long-term resorption/remodeling or osteointegration behavior is unknown. The minimally invasive bone graft harvester is a novel tool, which performed satisfactorily under laboratory conditions, but clinical results are still missing.     

Minimally invasive bone harvesting tools

The most readily available source for autologous bone graft used in spinal fusion (the gold standard) is the iliac crest. However, the open surgical approach for harvesting corticocancellous iliac bone is associated with a marked increase in morbidity. This study suggests two alternatives to the traditional open harvesting procedure. For anterior interbody fusion procedures using a cage, the autologous bone is harvested regionally from a neighboring vertebral body. Alternatively, using minimally invasive techniques, a custom bone graft harvester with a flexible tube and cutting tip allows harvesting of autologous bone from ¶a single entry point at the iliac crest. The effect on the mechanical strength of a lumbar vertebra of removing a cylindrical regional bone graft was studied in a cadaveric model. The bone defect was filled using three different filler materials: a porous tricalcium phosphate plug, a porous tantalum plug, and a self-setting calcium phosphate cement. After plug removal, the vertebral body’s strength in flexion/compression loading was reduced significantly, but could be restored to at least intact values with any of the three filler materials. The minimally invasive bone graft harvester was tested in three cadaveric pelves. With the cutting tip being guided within the cortical boundaries of the pelvis, cancellous bone volumes of 10–20 cc could be harvested from each iliac bone. Regional bone graft harvest in anterior spine surgery is suggested to be anatomically safe and biomechanically acceptable. Any of the three filler materials can restore the vertebral body’s mechanical strength, but the filler’s long-term resorption/remodeling or osteointegration behavior is unknown. The minimally invasive bone graft harvester is a novel tool, which performed satisfactorily under laboratory conditions, but clinical results are still missing.     

A novel source of cancellous autograft for ACDF surgery: the manubrium

There are a variety of techniques and biologic options when performing interbody fusion during an anterior cervical discectomy and fusion (ACDF). Autologous graft provides high rates of fusion; however, complications associated with donor site morbidity from the iliac crest have prompted some surgeons to use alternative graft material. Ten patients (8 men, 2 women) with cervical radiculopathy underwent single-level ACDF with plate fixation, titanium mesh cage, and cancellous autograft from the manubrium. Cancellous bone was obtained through a cortical window on the anterior aspect of the manubrium through a 2-cm transverse incision. A minimum 1-year clinical and radiographic follow-up for all patients evaluated fusion rates, donor site morbidity, and patient satisfaction. All patients had immediate postoperative resolution of radicular symptoms and radiographic evidence of solid fusion within 3 months. No patient complained of donor site pain and narcotic pain medication was not required after discharge. No complications associated with the manubrium donor site were noted; however, 1 female patient was dissatisfied with its cosmetic appearance. The manubrium is an effective, safe, and technically facile source of autologous bone graft that yields high fusion rates and patient satisfaction in contemporary ACDF surgery. This new technique to obtain cancellous graft from the manubrium combines the advantages of autologous bone without the morbidity of iliac crest harvest.     

Safety of recombinant human bone morphogenetic protein-2 after spinal laminectomy in the dog

STUDY DESIGN: This was a randomized, blinded trial of the safety of the application of recombinant human bone morphogenetic protein (rhBMP)-2 or autologous bone graft onto a laminectomy defect of the dog in the presence or absence of a dural membrane puncture. OBJECTIVE: To test the safety of rhBMP-2 in an application in which direct contact of the material with neural tissue occurs. SUMMARY OF BACKGROUND DATA: Application of rhBMP-2 in laboratory animals stimulates local bone formation to effect spinal fusion and healing of segmental bone defects. The use of rhBMP-2 as a bone graft substitute in spinal fusion would eliminate donor site morbidity and may augment the rate of successful fusion. Because rhBMP-2 may unintentionally come in contact with neural tissue, the consequences of such a safety issue must be addressed in an animal model before human trials. METHODS: Twenty skeletally mature beagles underwent spinal exposure followed by bilateral laminectomy at L5. In half of the dogs, a puncture wound was made to the dura with the expression of cerebrospinal fluid at the site of the puncture. In randomly selected animals, the exposed dural elements received either autologous bone graft with the bone removed from the laminectomy site or an implant of the rhBMP-2 device. The animals was observed for 12 weeks with periodic clinical examinations and monthly computed tomographic scans. RESULTS: There was no clinical, radiographic, or histologic evidence of neurologic abnormalities in these animals. The rhBMP-2 stimulated bone growth in the laminectomy defect and came into direct contact with the dural membrane. There was no evidence of abnormal mineralization within the thecal sac or in the spinal cord itself. CONCLUSIONS: The rhBMP-2 implant stimulated bone formation in the laminectomy site. Neither autologous bone, rhBMP-2, nor the dural puncture had deleterious consequences for the animals.     

rhBMP-2复合物与自体骨移植后腰椎融合率的系统评价

目的分析比较rhBMP-2复合物与自体髂骨移植后植骨融合率的差异。方法检索Cochrane liabrary（CCTR）以及Cochrane协作网专业试验数据库，MEDLINE（1966～2006），EMBASE（1980～2006），PUBMED（1966～2006），NRR（http：//www．update-software．com／National），CCT（http：//www．controlled-trials．com）。收集了有关rhBMP-2复合物与自体髂骨应用于腰椎手术的临床随机对照试验。统计软件采用Cochrane协作网提供的RevMan4．2．9。结果共纳入有关rhBMP-2复合物与自体髂骨应用于脊柱手术中的临床随机对照试验4篇共364例患者。Meta分析表明，rhBMP12复合物对比自体髂骨在治疗腰椎疾病的手术当中，术后6个月、12个月及24个月的植骨融合率明显高于自体髂骨。结论rhBMP-2复合物用于腰椎疾病的手术治疗时，其中、远期植骨融合率的效果明显优于自体髂骨。     

Experimental posterolateral spinal fusion with beta tricalcium phosphate ceramic and bone marrow aspirate composite graft

Background:

Beta tricalcium phosphate is commonly used in metaphyseal defects but its use in posterolateral spinal fusion remains controversial. There are very few published animal studies in which use of beta tricalcium phosphate has been evaluated in the posterolateral lumbar arthrodesis model. Hence we conducted a study to evaluate the potential of composite graft of beta tricalcium phosphate and bone marrow aspirate in comparison to autologous bone graft, when used for posterolateral spinal fusion.

Materials and Methods:

Single level posterolateral lumbar fusion was performed in 40 adult male Indian rabbits, which were assigned randomly into one of the four groups based on graft materials implanted; a) 3 gm beta tricalcium phosphate plus 3 ml bone marrow aspirate (Group I); b) 3 ml bone marrow aspirate alone (Group II); c) 3 gm beta tricalcium phosphate (Group III) and d) 3 gm autologous bone graft (Group IV). Each group had 10 rabbits. Half of the rabbits were sacrificed by injecting Phenobarbitone intraperitoneally after eight weeks and the remaining after 24 weeks, and were evaluated for fusion by X-rays, computed tomography (CT) scans, manual palpation test and histology.

Results:

Beta tricalcium phosphate used with bone marrow aspirate produced best results when compared to other groups (P =.0001). When beta tricalcium phosphate was used alone, fusion rates were better as compared to fusion achieved with autologous iliac crest bone graft though statistically not significant (P =0.07). Autologous bone graft showed signs of new bone formation. However, the rate of new bone formation was comparatively slow.

Conclusion:

Composite graft of beta tricalcium phosphate and bone marrow aspirate can be used as an alternative to autologous iliac crest bone graft.     

Anterior lumbar interbody fusion using rhBMP-2 with tapered interbody cages

In a multicenter, prospective, randomized, nonblinded, 2-year study, 279 patients with degenerative lumbar disc disease were randomly divided into two groups that underwent interbody fusion using two tapered threaded fusion cages. The investigational group (143 patients) received rhBMP-2 on an absorbable collagen sponge, and a control group (136 patients) received autogenous iliac crest bone graft. Plain radiographs and computed tomographic scans were used to evaluate fusion at 6, 12, and 24 months after surgery. Mean operative time (1.6 hours) and blood loss (109.8 mL) were less in the investigational rhBMP-2 group than in the autograft control group (2.0 hours and 153.1 mL). At 24 months the investigational group's fusion rate (94.5%) remained higher than that of the control group (88.7%). New bone formation occurred in all investigational patients. At all intervals, mean postoperative Oswestry, back pain, and leg pain scores and neurologic status improved in both treatment groups with similar outcomes. In the control group, eight adverse events related to the iliac crest graft harvest occurred (5.9%), and at 24 months 32% of patients reported graft site discomfort and 16% were bothered by its appearance. Lumbar fusion using rhBMP-2 and a tapered titanium fusion cage can yield a solid union and eliminate the need for harvesting iliac crest bone graft.     

颈椎椎间融合器融合效果的在体动物研究

目的在活体山羊颈椎上比较三面皮质自体骨、垂直圆柱体Harmscage及方盒形Carboncage的椎间融合效果。方法取24只成年雄性山羊,随机分为三组:自体骨组、Harmscage组及Car-boncage组。所有动物均行C3-4椎间盘切除术并分别植入以上内植物。于术前、术后即刻及术后1、2、4、8、12周摄颈椎正侧位X线片,于侧位X线片上测量平均椎间高度、椎间角及前凸角;术后12周处死动物,取C3,4节段标本进行组织学评估。结果术后1周Carboncage组的平均椎间高度、椎间角及前凸角大于Harmscage组和自体骨组(P<0.05);术后12周两个cage组的平均椎间高度、椎间角及前凸角均大于自体骨组,差异有统计学意义(P<0.05)。术后12周依据融合分级标准对三组进行影像学评估,和自体骨组比较,两个cage组的骨融合效果略好,但无统计学意义;组织形态学亦发现两个cage组的椎间融合效果较好,但与自体骨组比较差异无统计学意义。垂直圆柱体Harmscage中形成的新生骨量多于方盒形Carboncage。结论方盒形Carboncage具有良好的椎间支撑能力,而垂直圆柱体Harmscage的椎间融合效果更好。     

Bone grafting and substitutes in spine surgery

The increase of spinal procedures over the last decades has made the long-term problems, such as pseudarthrosis, apparent. This demands optimized strategies, techniques and technologies. Modern fixation systems have been developed as an adjunct to spinal fusion, and several generations of different synthetic cages have proved to be reasonable alternatives to autologous bone or allografts. The development of recombinant bone morphogenetic proteins (BMPs) is of promise, because of their great osteoinductive capabilities. While spine surgeons are familiar with autologous and synthetic grafts as well as allografts, these comparably new evolving growth-factor-based technologies are of high interest. This was a selective literature review. Alternatives to autologous grafts include allograft bone, synthetic cages and growth-factor based bone substitutes, BMPs being the most-studied among them. Autologous iliac crest alone provides all of the required capabilities of an ideal bone graft, i.e. osteoconduction, osteoinduction, osteogenesis, but each of the alternatives can produce excellent results in a number of indications. If combined, these alternatives can cumulatively provide all required graft capabilities. Nevertheless, all of the available grafts have specific characteristics and can feature certain complications. Alternatives to autologous grafts circumvent donor-site morbidity and are available in a larger amount than autologous bone for extensive surgery. New technologies offer excellent possibilities of new bone formation, but there are also severe risks and high costs to be considered. The indication for bone grafting must be clearly defined, the graft selection should be individually adapted, and the risks, efforts and costs of the selected fusion procedure should be carefully considered.     

Use of rhBMP-2 in combination with structural cortical allografts: clinical and radiographic outcomes in anterior lumbar spinal surgery

BACKGROUND: Recombinant human bone morphogenetic protein-2 soaked into an absorbable collagen sponge (rhBMP-2/ACS) has been shown in a nonhuman primate study and in a pilot study in humans to promote new bone formation and incorporation of an allograft device when implanted in patients undergoing anterior lumbar interbody arthrodesis. However, a larger series with longer follow-up is needed to demonstrate its superiority to autogenous iliac crest bone graft. METHODS: Between 1998 and 2001, a two-part, prospective, randomized, multicenter study of 131 patients was conducted to determine the safety and efficacy of the use of rhBMP-2/ACS as a replacement for autogenous iliac crest bone graft in anterior lumbar spinal arthrodesis with threaded cortical allograft dowels. Patients were randomly assigned to a study group that received rhBMP-2/ACS or to a control group that received autograft. The clinical and radiographic outcomes were determined with use of well-established instruments and radiographic assessments. RESULTS: The patients in the study group had significantly better outcomes than the control group with regard to the average length of surgery (p < 0.001), blood loss (p < 0.001), and hospital stay (p = 0.020). Fusion rates were significantly better in the study group (p < 0.001). The average Oswestry Disability Index scores, Short-Form-36 physical component summary scores, and low-back and leg-pain scores were significantly better in the study group (p < 0.05). CONCLUSIONS: In patients undergoing anterior lumbar interbody arthrodesis with threaded allograft cortical bone dowels, rhBMP-2/ACS was an effective replacement for autogenous bone graft and eliminated the morbidity associated with graft harvesting.     

Complications following autologous bone graft harvesting from the iliac crest and using the RIA: a systematic review

Bone grafting is a commonly performed surgical procedure to augment bone regeneration in a variety of cases in orthopaedic and maxillofacial surgery. Autologous bone graft remains to be the 'gold standard' and the iliac crest to be the most common harvesting site. The intramedullary canal of long bones represents another potential site for large volume of autologous bone graft harvesting and is recently being used as an alternative donor site. However, harvesting of autologous bone graft is associated with morbidity and a number of complications. The aim of this systematic review was to collect and summarise the existing data on reported complications after harvesting autologous bone from the iliac crest (anterior and posterior) and the long bone intramedullary canal using the RIA device. We searched the PubMed Medline and Ovid Medline databases, from January 1990 to October 2010, to retrieve all relevant articles. A total of 92 articles (6682 patients) were included in the analysis. Overall, the complication rate following RIA was 6% (14 complications in 233 patients) and 19.37% after iliac crest bone graft harvesting (1249 complications in 6449 patients). The rate of each of the reported complications was assessed and, when the donor site was properly documented, comparison within the anterior and posterior iliac crest donor sites was performed. Although the difference of the overall morbidity rates between the two harvesting sites was not statistically significant (p=0.71); the rates of certain complications were found to significantly differ when anterior or posterior iliac crest was used. The rates of infection (p=0.016), haematoma formation (p=0.002), fracture (p=0.017), and hyperthrophic scar (p=0.017) were significantly higher when the donor site was the anterior iliac crest compared to the posterior iliac crest; whereas the rates of chronic donor site pain (p=0.004) and sensory disturbances (p=0.003) were significantly lower. The incidence of bone graft harvesting related complications can be reduced further if certain principles are followed depending on the performed harvesting methods; but overall the use of RIA device as harvesting method seems a promising alternative with a low complication rate.