Demineralized bone matrix composite grafting for posterolateral spinal fusion

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

骨髓干细胞复合纳米骨用于脊柱融合的研究

目的 探讨骨髓间充质干细胞(BMSCs)复合纳米羟基磷灰石/胶原(nHAC)用于脊柱融合的可行性.方法 将20只新西兰大白兔根据双侧L5～L6横突间植入物不同分为复合材料组和自体髂骨组,每组10只.术后4周每组取材2只,术后8周取材剩余兔,行X线、大体观察、手触检测和组织学观察,评估腰椎融合情况.结果术后8周复合材料组和自体髂骨组融合率分别为75.0%(6/8)和87.5%(7/8),两组融合率差异无统计学意义(P>0.05).结论 BMSCs复合nHAC是一种较好的植骨替代材料,用于脊柱融合可获得与自体骨移植近似地融合效果.     

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

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

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.     

应用脱钙骨基质和硫酸钙颗粒治疗骨缺损的初期结果

目的探讨使用骨移植替代物脱钙骨基质（DBM）和硫酸钙颗粒（OSTEOSET）治疗骨缺损的疗效。方法对同期手术治疗的52例骨缺损患者的缺损处,分别于术后第1、4、8周及3、6、12个月进行随访并摄X线片直至骨缺损愈合。统计分析患者的临床资料、X线片辅助分析骨缺损修复程度和并发症。结果随访8-12个月,植骨术后6、12个月分别有95%和99%患者的骨缺损显示有明显的新骨形成,修复水平为60%-100%。并发症为3例（5.77%）,经换药后治愈,未发生骨缺损不愈合。结论DBM和OSTEOSET在骨愈合早期可加速骨缺损的修复,并可作为新鲜自体髂骨的替代物。     

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

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

Osseous healing with a composite of allograft and demineralized bone matrix: adverse effects of smoking

We report on our use of a composite graft of lyophilized cancellous allogenic chips and demineralized bone matrix (DBM; Grafton; Osteotech, Eatontown, NJ) to manage traumatic osseous defects and nonunions. Data were prospectively collected from all patients who received this composite bone graft between 1996 and 2000. Only acute fractures with bone loss resulting in a uncontained defect and atrophic non-unions were included in the present study. Demographic data and complications related to composite use, tobacco use, and other comorbidities that could affect healing were evaluated. One hundred seven patients (112 bone graft sites) were followed up for a mean of 32 months (range, 12-60 months). Graft sites included the forearm, femur and tibia. Of the 112 patients, there were 56 smokers (25 non-unions and 31 fractures) and 56 non-smokers (28 fractures and 28 non-unions). Healing occured in 38/56 smokers compared with 49/56 non-smokers. In failed cases, smoking was characteristic in 7/9 non-unions and 11/16 fractures. There were 26 acute uncontained injuries, 29 acute contained defects, and 67 nonunions. Grafting sites were radius/ulna (13 cases), humerus (17), femur (31), and tibia/fibula (51). Significant comorbidities were diabetes mellitus (4 cases), fungal osteomyelitis (1), and pulmonary alveolar proteinosis (1). Eight (73%) of the 11 patients with graft failure had a significant smoking history. This composite graft is an option for managing osseous defects and nonunions traditionally treated with autologous bone grafting but should be used with caution when treating patients who are smokers.     

自体骨髓、骨联合移植在脊柱融合中的应用

目的 探讨自体骨髓、骨联合移植在脊柱融合中的运用。方法 84例中2例半椎体畸形、8例胸椎及胸腰椎结核、10例椎体滑脱、4例下颈椎骨折、51例胸腰段骨折、6例腰椎骨折及3例退变节段不稳患者在处理原发病的同时行植骨融合术，二期再在X线监视下行经皮注射自体骨髓移植，其中74例合并应用内固定器。结果 78例获得随访，平均随访期30．06个月。75例融合成功。3例失败，其中2例二次取内固定术中才被发现，第3例术后8个月X线片有假关节形成表现，再次术中也证实有假关节形成。无神经系统症状加重的病例出现。结论 骨髓、骨联合移植在脊柱融合中运用失败率低(3．85％)，成骨性强、生物安全性好。     

Treatment of nonunion by percutaneous injection of bone marrow and demineralized bone matrix. An experimental study in dogs

Successful treatment of nonunited fractures remains a major clinical challenge. Because bone marrow and demineralized bone matrix (DBM) are capable of stimulating osteogenesis, experiments were designed to test the effectiveness of bone marrow or DBM or both when injected percutaneously into a canine nonunion model. Six-millimeter segmental defects were created in the midtibial diaphysis of 24 adult mongrel dogs and held distracted by external fixation. For comparative purposes, a 0.5-mm osteotomy was created in five dogs. Five weeks later, the 6-mm defects were injected with either saline, autogeneic marrow, DBM powder, a composite of bone marrow and DBM, or treated by open grafting techniques with autogenic cancellous bone. Healing of the defect was evaluated roentgenographically, biomechanically (three-point bending), histologically, and biochemically 13 weeks postsurgery. Marrow and DBM stimulated defect healing. However, the combination of bone marrow with DBM produced a synergistic response in the defect, which was greater than the sum of either marrow or DBM alone. Healing in the composite-grafted dogs was comparable to those treated by standard cancellous bone grafting. These data suggest that percutaneous injection of bone marrow and DBM may be a potential alternative that offers numerous advantages over standard open grafting techniques in the treatment of fractures with nonunited defects.     

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

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

干细胞技术结合新型可降解材料进行腰椎融合的临床研究

目的 探索富集骨髓干细胞技术进行腰椎融合治疗脊柱疾病的疗效.方法 腰椎退行性疾患患者56例,根据行下腰椎后路融合手术中植骨融合材料的不同,分为富集骨髓干细胞快速复合多孔β-磷酸三钙(13-TCP)复合材料组(复合材料组,n=30)和自体髂骨植骨组(自体骨组,n=26).对复合材料组富集前后骨髓体积、有核细胞(NCs)和碱性磷酸酶染色阳性的细胞集落(CFUs/ALP+)计数,分析富集效率;结合随访、影像学检查和Oswestry功能评分等综合评定疗效.结果 复合材料组术中平均抽取骨髓血(249±31)ml,富集技术平均回收(43±11)ml,NCs由(15.9±3.3)x106/ml浓缩至(44.1±10.8)×106/ml,富集后CFUs/ALP+数量由(118±86)/ml浓缩至(486±305)/ml.临床随访(26.3±7.5)个月.两组中患者的年龄、性别、病种分布及融合节段无显著差异,复合材料组与自体骨组融合率分别为93.3%和96.2%(P＞0.05).两组手术时间的差异也无统计学意义(P＞0.05).复合材料组术中患者的总出血量高于自体骨组(P＜0.01),但术中自体血回输可以将接近1/2的术中出血回输给患者.复合材料组术后骨髓采集部无血肿和慢性疼痛,伤口渗出或局部肿胀4例,均自行愈合;而自体骨组术后髂骨采集部血肿(15.4%)和慢性疼痛(26.9%),无伤口渗出的情况.两组间Oswestry功能评分的差异无统计学意义(P＞0.05).结论 富集骨髓干细胞技术可在术中一期应用,提高骨髓MSCs的浓度,安全、快速.富集骨髓干细胞快速复合多孔β-磷酸三钙后,可作为腰椎后外侧融合的植骨替代品.     

The effect of demineralized bone matrix-calcium sulfate with vancomycin on calcaneal fracture healing and infection rates: a prospective study

BACKGROUND: Displaced intra-articular calcaneal fractures may have a central cancellous bone defect area. We hypothesized that human demineralized bone matrix (DBM) calcium sulfate (CaSO(4)) might act as a reasonable alternative to autograft in calcaneal fractures. When combined with antibiotic powder, this bone graft substitute also may act as a local antibiotic delivery device. This is the first clinical study evaluating bone healing and complications associated with DBM-calcium sulfate bone graft substitute in the treatment of displaced intra-articular calcaneal fractures with a central cancellous bone defect. METHODS: Over a 29-month period, 33 displaced intra-articular calcaneal fractures with central cancellous defects were treated with open reduction and internal fixation (ORIF) and grafting with vancomycin/DBM-calcium sulfate bone graft substitute. Eleven fractures without bone defects were treated with ORIF only. Patient demographics, medical history, and CT fracture classification were recorded. Postoperatively, fractures were monitored every 2 weeks for healing and complications. RESULTS: The mean time to union was 8.2 weeks in the grafted, while the control group mean time to union was 10.4 weeks (p = 0.0117). Wound problems occurred in five (15%) of the 33 patients with grafting, all in type III fractures with severe soft-tissue swelling, and included two minor wound healing delays, and three serious wound problems. At a mean followup time of 22.4 months, no DBM-calcium sulfate grafted calcaneus demonstrated evidence of osteomyelitis. CONCLUSIONS: This is the first study examining human DBM-calcium sulfate bone graft substitute to treat displaced intra-articular calcaneal fractures. Based on these initial data, human DBM-calcium sulfate acted as an acceptable and safe autograft alternative in displaced intra-articular calcaneal fractures with moderate (5 cc to 10 cc) central cancellous bone defects.     

脱钙骨基质治疗长骨骨折延迟愈合及骨不连

目的探讨脱钙骨基质(decalcifiedbonematrix,DBM)治疗长骨骨折延迟愈合和骨不连的疗效。方法长骨延迟愈合、骨不连共57例,男45例,女12例;年龄21~65岁,平均42岁。开放性骨折17例,闭合骨折40例。骨折延迟愈合32例中,肱骨4例,股骨10例,胫骨18例;骨不连25例中,肱骨5例,股骨4例,胫骨16例。全部采用DBM于骨断端处和骨缺损区植入治疗。结果57例患者均获随访,随访时间4~37个月,平均7.8个月。骨折延迟愈合32例中骨折愈合31例,1例胫骨骨折未愈合;骨不连25例中骨折愈合23例,2例未愈合,其中胫骨1例、肱骨1例。愈合时间3~6.6个月,平均4.7个月。结论DBM治疗长骨骨折延迟愈合及骨不连,其疗效满意、并发症少。     

Combined autologous cellular cardiomyoplasty with skeletal myoblasts and bone marrow cells in canine hearts for ischemic cardiomyopathy

OBJECTIVES: Cellular cardiomyoplasty with isolated skeletal myoblasts and bone marrow mononuclear cells is an encouraging therapeutic strategy for heart failure. We investigated the achievements accomplished with combined cell therapy of skeletal myoblast and bone marrow mononuclear cell transplantation to the ischemic canine myocardium. METHODS: Autologous skeletal myoblasts (1 x 10(8)) and autologous bone marrow mononuclear cells (3 x 10(6)) were injected directly into the damaged myocardium of canine hearts that had undergone 2 weeks of left anterior descending coronary artery ligation. Treatment groups were as follows: skeletal myoblasts plus bone marrow mononuclear cells (combined cell therapy, n = 4), myoblasts (n = 4), bone marrow mononuclear cells (n = 4), and medium only (n = 4). In similarly designed supporting experiments, angiogenic factor expression was evaluated by enzyme-linked immunosorbent assay after cell transplantation in rat hearts that had undergone left anterior descending coronary artery ligation. RESULTS: Four weeks after cell implantation, echocardiography demonstrated better cardiac performance with reduced left ventricular dilation and significantly improved ejection fraction in the combined cell therapy group compared with that seen in the other groups (pretreatment, 37.7% +/- 1.1%, vs combined cell therapy, 55.4% +/- 8.6%; myoblasts, 47.4% +/- 7.4%; bone marrow mononuclear cells, 44.4% +/- 6.7%; medium only [control], 34.4% +/- 5.4%; P < .05). A significantly high number of neovessels were observed in the group receiving combined cell therapy only (combined cell therapy, 45.5 +/- 12 x 10(2)/mm2; myoblasts, 26.5 +/- 8 x 10(2)/mm2; bone marrow mononuclear cells, 30.7 +/- 15 x 10(2)/mm2; medium only [control], 7.1 +/- 1 x 10(2)/mm2; P < .05). Immunostained sections expressed the skeletal specific marker myosin heavy chain, although they did not express the cardiac specific marker troponin T. Results of enzyme-linked immunosorbent assay showed the highest expression of vascular endothelial growth factor (combined cell therapy, 2.9 +/- 0.7 ng/g tissue; myoblasts, 0.24 +/- 0.7 ng/g tissue; bone marrow mononuclear cells, 1.9 +/- 0.2 ng/g tissue; medium only [control], 0.19 +/- 0.004 ng/g tissue; P < .05) and hepatocyte growth factor in the combined cell therapy hearts. CONCLUSIONS: Combined autologous cellular therapy induced both myogenesis and angiogenesis with enhancement of cardiac performance and reduction of cardiac remodeling, suggesting a capable strategy for treating severe ischemic cardiomyopathy clinically.     

Augmented demineralized bone matrix: a potential alternative for posterolateral lumbar spinal fusion

Variable osteoinductive potential has been reported between and within production lots of different demineralized bone matrix (DBM) products. This study compared fusion rates of different manufactured lots and augmented formulations of DBM with a dose-response curve of recombinant human bone morphogenetic protein 2 (rhBMP-2) on inactivated DBM carrier in a posterolateral fusion rat model. Lumbar fusions were performed in 145 rats. In the control rats, we implanted autograft, graft alternative, including inactivated DBM, or nothing (ie, no graft). In the study rats, we implanted 1 of 2 BioSETR (RTI Biologics, Alachua, Florida) DBM lots, growth factor-enriched DBM, and inactivated DBM plus rhBMP-2 in different concentrations. Manual palpation revealed fusion rates of 25% (autograft), 0% (inactivated DBM), 17% (DBM donor A), and 36% (DBM donor B). The fusion rate of the most enhanced donor B graft (83%) was higher (P<.05) than that of autograft or unenhanced DBM. Inactivated DBM plus rhBMP-2 fused between 45% and 100%. There was no significant difference between DBM plus rhBPM-2 and the highest enrichment group of donor B. Differences between 2 DBM lots in an athymic rat ectopic bone formation model also were found in the spine fusion model. Enhanced DBM formulations were comparable with inactivated DBM plus rhBMP-2 with respect to performance and could represent a bone graft alternative in spine fusion.     

Multicenter trial of Collagraft as bone graft substitute

Collagraft (Zimmer and Collagen Corporation) consists of a mixture of porous beads composed of 60% hydroxyapatite and 40% tricalcium phosphate ceramic and fibrillar collagen. When mixed with autogenous bone marrow, it serves as an effective bone graft substitute. Since September 1986, this material has been used in a multiclinic prospective trial, randomized against cancellous iliac crest autografts in the treatment of long bone fractures. To date, 267 patients have entered this study with 128 patients receiving cancellous autograft and 139 patients receiving Collagraft. At 6- and 12-month follow-ups, Collagraft appears to function as well as autogenous graft when used in the treatment of acute long bone fractures.     

Adjuncts in posterior lumbar spine fusion: comparison of complications and efficacy

Purpose

The purpose of this study was to define the efficacy of recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) and Demineralized Bone Matrix (DBM) compared to autograft in posterior lumbar spine fusion by comparing complication rates.

Methods

During a 7-year period (2003–2009), all patients undergoing posterior lumbar fusion were retrospectively evaluated within a large orthopedic surgery private practice. Patient demographics, comorbidities, number of levels, type of surgery, and types of bone void filler and osteobiologics were analyzed. Complications were defined as reoperation secondary to failed symptomatic fusion, hyper-reaction with fluid collections, bone overgrowth, and infections.

Results

1,398 patients were evaluated with 41.1?% males and 58.9?% females. Mean age was 60?years and BMI 30.6?kg/m2. Patients were subdivided in treatment groups: rhBMP-2, 947 (67.7?%), DBM 306 (21.9?%), and autograft 145 (10.4?%). The overall infection rate was 2.1?%. No significant differences were found between the three groups. The incidence of seroma formation was higher in the BMP group (3.2?%) than in the DBM or autograft group (2.0 and 1.4?%, respectively) but this was not significant (p?=?0.286 and p?=?0.245, respectively). 103 patients (7.4?%) underwent redo surgery for clinically significant nonunion. We found significantly fewer nonunions (4.3?%) in the rhBMP-2 group (p?Conclusion ICBG is the gold standard. DBM leads to comparable fusion rates and does not increase infection or seroma formation. rhBMP-2 supplementation instead of ICBG or bone marrow aspirate results in higher fusion rates compared to autograft alone or autograft plus DBM.     

Mechanisms of bone loss following allogeneic and autologous hemopoietic stem cell transplantation.

A significant proportion of patients will be long-term survivors of bone marrow transplantation (BMT) and little is known about their risk of late bony complications. We therefore evaluated bone mineral density (BMD) prior to BMT, post-transplantation changes in BMD, and mechanisms of bone loss in long-term survivors. We performed two analyses. The first was a cross-sectional study of 83 consecutive BMT patients (38 F, 45 M), examining the relationship between BMD and bone turnover, measured immediately prior to transplantation, and a number of disease and patient variables. The second was a prospective study of 39 patients (19F, 20 M) followed for a median of 30 months (range 5-64 months) following either allogeneic (allo, n = 29) or autologous (auto, n = 10) BMT to determine if bone loss was related to treatment of graft versus host disease (GVHD) with glucocorticoids and cyclosporine A, high bone turnover rates, or hypogonadism. Auto BMT recipients acted as a control group for effects of GVHD therapy on BMD. Prior to BMT, spinal and femoral neck (FN) BMDs were 8.6% and 14% lower in female auto BMT recipients than in female allo BMT recipients, respectively (p = 0.12 and p = 0. 003). Urinary bone resorption markers were higher than in normal gender- and age-matched control subjects. Patients treated previously with glucocorticoids also had 8% lower FN BMD. Glucocorticoid-pretreated women with amenorrhoea had lower lumbar spine (LS) and FN BMDs than eumenorrheic women and women receiving HRT. Post-allo BMT, patients lost 11.7% of FN BMD compared with a nonsignificant decrease of 1.1% post-auto BMT (p < 0.001). Spinal BMD and total body bone mineral content (TBBMC) decreased by 3.9% and 3.5%, respectively, post-allo, compared with an increase (1.5%, p = 0.03) or nonsignificant decrease (-3.7%, p = NS), respectively, post-auto BMT. Post-allo BMT bone loss correlated best with the cumulative prednisolone dose at the LS and FN, and with average daily prednisolone dose for TBBMC. At the spine, the rate of bone loss was 4%/10 g of prednisolone, while the rate of bone loss at the FN was greater (9%/10 g of prednisolone). Bone loss was also negatively related to the duration of cyclosporine therapy for GVHD and baseline deoxypyridinoline concentrations. Avascular necrosis of the femoral head occurred in four, and vertebral and rib fractures occurred in one of the allo BMT patients, but in no auto BMT patients. In conclusion, BMT recipients are at risk of osteoporosis secondary to bone loss associated with their underlying illness and/or chemotherapy, particularly in female autograft recipients, and in allograft recipients secondary to GVHD and its treatment.     

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

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

糖尿病足患者骰骨病变的MRI和X线特征

目的分析糖尿病足(DF)患者骰骨病变的MRI及X线表现。方法回顾性分析124例不同类型的足部病变患者的MRI、X线资料,其中DF组54例,非DF组70例,观察两组患者骰骨信号改变、单纯骨髓水肿、骨髓水肿合并骨折、骰骨与周围骨的关系的MRI、X线的差异。结果两组患者骰骨信号改变、单纯骨髓水肿、骨髓水肿合并骨折的差异均有统计学意义(P均0.05)。DF组中,18例(18/54,33.33%)表现为单纯骨髓水肿,T1WI呈等低信号,T2WI呈高信号,增强扫描无明显强化;非DF组中,8例(8/70,11.43%)单纯骨髓水肿。DF组中,6例(6/54,11.11%)表现为骨髓水肿合并骨折,骨折T1WI呈线样、模糊低信号影,骨皮质不连续,仅1例骰骨骨折X线平片可见;非DF组中,1例(1/70,1.43%)表现为骨髓水肿合并骨折,X线平片不可见。DF组,1例骰骨骨髓炎,3例骰骨周围关节腔积液,2例合并夏科关节病;非DF组1例可见关节腔积液。结论 DF患者较非DF患者骰骨更易受损,出现骨髓水肿和骨折,结合MR影像特征有利于对DF患者骰骨病变的诊断。