Percutaneous autologous bone marrow transplantation for nonunion of the femur.

Percutaneous bone marrow injections were performed on 7 nonunions of the femur. There were 6 hypervascular nonunions and one avascular nonunion. Two nonunions presented with active infections. One other patient had a history of infection which had subsided. One nonunion received the injection twice. After the site of nonunion was curetted and the bone surface was scored, 150 ml of bone marrow aspirated from the iliac bone was injected. Complete union occurred in 4 patients within 9 months; all of them were uninfected hypervascular nonunions following intramedullary nail fixation. One nonunion with a bone defect united partially leaving a 1 x 1 cm defect. The two infected femoral nonunions failed to unite. The results show that percutaneous autologous bone marrow injection for femoral nonunions can be considered for uninfected hypervascular nonunions following intramedullary nail fixation. In these cases stimulation of healing processes of fracture leading to consolidation can be expected from bone marrow injection. However, femoral nonunion with an active infection and loss of fixation is considered to be a contraindication for this technique.     

Local transplantation of bone marrow concentrated granulocytes precursors can cure without antibiotics infected nonunion of polytraumatic patients in absence of bone defect

Purpose

Infected, long bone non-unions present a significant clinical challenge. New and alternative therapies are needed to address this problem. The purposes of this study were to compare the number of circulating granulocyte-macrophage colony-forming units (CFU-GM) in the peripheral blood of polytraumatic patients with infected tibial non-unions and in the peripheral blood of control patients with the hypothesis that their number was decreased in polytraumatic patients; and to treat their infection without antibiotics and with local transplantation of bone marrow concentrated granulocytes precursors.

Methods

Thirty (18 atrophic and 12 hyperthrophic ) infected tibial non-unions (without bone defect) that occurred after open fractures in polytraumatic patients were treated without antibiotics and with percutaneous injection of autologous bone marrow concentrate (BMC) containing granulocytes precursors (CFU-GM). CFU-GM progenitors were assessed in the bone marrow aspirate, peripheral blood, and fracture site of these patients. The number of these progenitors was compared with the CFU-GM progenitors of control patient samples (healthy donors matched for age and gender). Outcome measures were: timing of union, callus formation (radiographs and CT scan), and recurrence of clinical infection.

Results

As compared to control patients, the number of CFU GM derived colonies was lower at peripheral blood in patients with infected nonunions. The bone marrow graft injected in nonunions contained after concentration 42 621?±?20 350 CFU-GM-derived colonies/cc. Healing and cure of infection was observed at six months for 25 patients and at one year follow up for 30 patients. At the median ten year follow-up (range: 5 to 15), only one patient had clinical recurrent infection after healing (between 6 months and last follow-up).

Conclusion

The peripheral blood of these polytraumatic patients with infected nonunions had a remarkable decrease in CFU-GM-derived colonies as compared with normal controls. Local transplantation of concentrated CFU-GM-derived colonies aspirated from bone marrow allowed cure of infection and healing without antibiotics.

     

经皮自体骨髓移植治疗骨折不愈合

目的 探讨经皮自体骨髓移植治疗骨折不愈合的疗效。方法 治疗患者３１例,男２５例,女６例;年龄１８￣７７岁,平均２７岁。骨不连部位：肱骨７例,腕舟骨１２例,股骨５例,胫骨７例。骨不连时间７￣４８个月,平均１３个月。治疗方法：在Ｘ线电视透视下将一枚骨穿针准确穿入骨不连部位,然后抽取自体髂骨红骨髓即刻注入骨不连部位。腕舟骨注射１０￣１５ｍｌ,一次即可;四肢长骨注射３０￣５０ｍｌ,需２￣３次,间隔３￣４周     

Percutaneous autologus bone marrow injection in the treatment of delayed or nonunion

Background:

Bone marrow is a source of osteoprogenitor cells that are key elements in the process of bone formation and fracture healing. The purpose of the study was to ascertain the osteogenic potential of autologous bone marrow grafting and its effectiveness in the management of delayed union and nonunion.

Materials and Methods:

Twenty-eight patients with delayed union and three with nonunion of fracture of the long bones were treated with this procedure. Of these 28 cases, two patients had fracture shaft femur, one had fracture shaft ulna and 25 patients had tibial shaft fractures. The average time duration between procedure and injury was 25 weeks (range 14-53 weeks). The bone marrow was aspirated from the anterior iliac crest and injected percutaneously at the fracture site. The procedure was carried out as an outpatient procedure. All but five cases required one injection of bone marrow.

Results:

Union was observed in 23 cases. The average time of healing after the procedure was 12 weeks (range 7-18 weeks).

Conclusion:

The technique of percutaneous autologous bone marrow injection provides a very safe, easy and reliable alternative to open bone grafting, especially for early intervention in fracture healing process.     

Percutaneous bone marrow grafting for the treatment of tibial non-union

This is a prospective study to evaluate the efficacy of percutanous bone marrow grafting in patients with established tibial non-union and minimal deformity, whilst on the waiting list for open surgical procedures. Twenty consecutive patients with established tibial non-union and minimal deformity were treated by percutanous bone marrow injection under local anaesthesia. Bone marrow was obtained from the iliac crest, 3-5 ml of marrow was aspirated and injected immediately into and about the non-union site. Subsequent aspirations were performed 1 cm posterior to the previous site until a maximum of 15 ml of marrow was injected. Our results revealed clinical and radiological bone union following percutanous injection in 15 out of 20 patients (75%), with an average time to union following the first injection of 14 weeks. Four patients (20%) showed no evidence of union and were considered a failure. There were no cases of infection following the injection, and no complications at the donor site. We conclude that percutanous bone marrow grafting is a safe, simple, and reliable method of treating tibial non-union with minimal deformity. It is a limited invasive technique with minimal complications. It can be performed under local anaesthesia, is cost effective and potentially can avoid major surgical reconstruction.     

Core decompression with marrow stem cells

Association of core decompression with technique of bone graft is frequent and many different techniques have been described. In this series, grafting was done with autologous bone marrow obtained from the iliac crest of patients operated for hips osteonecrosis. The bone marrow was harvested under general anesthesia. A beveled metal trocar of 6 to 8 cm in length and a bore of 1.5 mm was pushed deep into the cancellous bone. A 10-mL syringe that has been flushed with heparin is used to aspirate the marrow. Once the needle has been inserted to the desired depth, the tip is swept around a full circle in 45° steps, with the bevel pointing in different directions at each step. This procedure is continued until a sufficient quantity of bone marrow has been harvested (150 mL). All the marrow aspirated is discharged into a plastic collection bag containing ACD (acid citrate dextrose) anticoagulant solution. It is then filtered, to remove fat aggregates and clots. The aspirated marrow was reduced in volume by concentration and injected in the femoral head after core decompression with a small trocar. To measure the number of progenitor cells transplanted, we used the fibroblast colony forming unit as an indicator of the stromal cell activity and performed in vitro cultures of the fibroblast progenitor cells. The average volume of bone marrow aspiration was 147 mL ± 12 mL per hip. The number of progenitor cells was average 12.4 ± 3.4 per 10⁶ bone marrow nucleated cells and the number of nucleated cells was estimated to be 16.4 million cells per milliliter of bone marrow.     

Surgical treatment of proximal ulna nonunion

We reviewed our experience in the surgical treatment of 12 cases of proximal ulna nonunion. The primary injuries were 2 fracture-dislocations of the olecranon, 6 Monteggia lesions and 3 isolated fractures of the proximal ulna. According to the type of primary injury and its anatomical site, the nonunions were classified into 2 groups, considering that the nonunions nearest to the humerus-ulna joint present a more disabling clinical profile and are more difficult to treat: group A (6 patients — nonunion within 5 cm from the olecranon tip of the olecranon) and group B (6 patients — nonunion between 5 and 10 cm from the olecranon tip of the olecranon). In all cases, after fibrous callus debridement and bone surface remodelling, fixation was performed with plate and screws and homoplastic cortical bone graft (orthogonal or parallel to the plate) and an intercalary bone cylinder when the bone defect was severe. In 3 patients (group A), where the defect was smaller than 1 cm, fixation of the ulna was combined with a resection of the radial neck. Clinical-radiographic healing was achieved in all patients followed for a mean of 27 months. Complications included a case of nonunion due to failure of the intercalary graft with plate breakage. The patient healed after a new surgery performed with same technique. The score, according to the Broberg-Morrey scoring system, was 78 in group A patients and 93 in group B patients. The use of homoplastic cortical bone graft represents an effective technique to improve the mechanical properties of the fixation and supports biological union, even when the bone defect is severe.     

Treatment of osteonecrosis with autologous bone marrow grafting

Core decompression with bone graft is used frequently in the treatment of osteonecrosis of the femoral head. Many different techniques have been described. In the current series, grafting was done with autologous bone marrow obtained from the iliac crest of patients operated on for osteonecrosis of the hip. The results of a prospective study of 189 hips in 116 patients treated with core decompression and autologous bone marrow grafting are reported. Patients were followed up from 5 to 10 years. The outcome was determined by the changes in the Harris hip score, by progression in radiographic stages, and by the need for hip replacement. The bone marrow was harvested with the patient under general anesthesia. The usual sites were the anterior iliac crests. The aspirated marrow was reduced in volume by concentration and injected into the femoral head after core decompression with a small trocar. When patients were operated on before collapse (Stage I and Stage II), hip replacement was done in nine of the 145 hips. Total hip replacement was necessary in 25 hips among the 44 hips operated on after collapse (Stage III and Stage IV). To measure the number of progenitor cells transplanted, the fibroblast colony forming unit was used as an indicator of the stroma cell activity. Patients who had the greater number of progenitor cells transplanted in their hips had better outcomes.     

Treatment of allograft nonunions with recombinant human bone morphogenetic proteins (rhBMP)

Fractures and nonunions are the main complications associated with bone allografts. Although the osteogenic role of recombinant human bone morphogenetic proteins (rhBMPs) has been demonstrated in experimental models and human tibial nonunions, the results are unknown for allograft nonunions. In this study, the efficacy of rhBMPs was evaluated in nonunions of femoral allografts. The results of six allograft nonunions in five patients who underwent resection of malignant bone tumours and allograft bone transplantation were analysed one to five years following application of rhBMPs at the nonunion site. There were two osteoarticular allografts and three intercalary allografts. Of three intercalary allografts, one demonstrated nonunion at both ends. Four patients received adjuvant chemotherapy and three had additional radiation therapy. There were two allograft fracture nonunions and four nonunions at the allograft-host junction. Two allograft fracture nonunions and one nonunion at the allograft-host junction were treated with 12 mg of rhBMP-2. The remaining three nonunions were treated with 7 mg of rhBMP-7 (Osigraft). The outcome and radiological evidence of healing were evaluated at a minimal follow-up of twelve months. There was neither healing of allograft fractures nor union of allograft-host junction. There was elongation or enlargement of the callus from the host. One patient continued to develop resorption of the allograft, which led to allograft fracture. Two patients who were treated with rhBMP-7 and corticocancellous allografts developed sterile drainage. There was no tumour recurrence with the use of rhBMPs after a mean follow-up of 39+/-25 months. rhBMP's alone were not sufficient to achieve healing in allograft nonunions and fractures following wide resection including periosteum and soft tissues.     

Treatment of nonunions and osseous defects with bone graft and calcium sulfate

The treatment of long bone nonunions and fractures with osseous defects is challenging. The results of 26 patients with either a persistent long bone nonunion or an osseous defect after an open fracture were reviewed. Each patient was treated with debridement of devitalized tissue, open reduction and internal fixation, and bone grafting using a mixture of autogenous iliac crest bone graft and medical grade calcium sulfate. The current study evaluated the union rate and associated complications for treatment of these injuries using this protocol. Each nonunion was confirmed intraoperatively, and healing was determined clinically by the patients' return to full activities without pain and radiographically by the presence of bridging trabeculae. Complications included persistent nonunion (four patients), wound drainage (five patients), wound drainage and cellulitis (one patient) and cellulitis alone (one patient). Using this treatment protocol, 22 patients (85%) achieved healing after one surgery and an additional two patients (92%) achieved healing after a second surgery. Medical grade calcium sulfate increases the volume of graft material, facilitates bone formation, and is safe in the treatment of nonunions and fractures with osseous defects.     

Ablation of Proliferating Osteoblast Lineage Cells After Fracture Leads to Atrophic Nonunion in a Mouse Model

Nonunion is defined as the permanent failure of a fractured bone to heal, often necessitating surgical intervention. Atrophic nonunions are a subtype that are particularly difficult to treat. Animal models of atrophic nonunion are available; however, these require surgical or radiation-induced trauma to disrupt periosteal healing. These methods are invasive and not representative of many clinical nonunions where osseous regeneration has been arrested by a “failure of biology”. We hypothesized that arresting osteoblast cell proliferation after fracture would lead to atrophic nonunion in mice. Using mice that express a thymidine kinase (tk) “suicide gene” driven by the 3.6Col1a1 promoter (Col1-tk), proliferating osteoblast lineage cells can be ablated upon exposure to the nucleoside analog ganciclovir (GCV). Wild-type (WT; control) and Col1-tk littermates were subjected to a full femur fracture and intramedullary fixation at 12 weeks age. We confirmed abundant tk+ cells in fracture callus of Col-tk mice dosed with water or GCV, specifically many osteoblasts, osteocytes, and chondrocytes at the cartilage-bone interface. Histologically, we observed altered callus composition in Col1-tk mice at 2 and 3 weeks postfracture, with significantly less bone and more fibrous tissue. Col1-tk mice, monitored for 12 weeks with in vivo radiographs and micro–computed tomography (μCT) scans, had delayed bone bridging and reduced callus size. After euthanasia, ex vivo μCT and histology showed failed union with residual bone fragments and fibrous tissue in Col1-tk mice. Biomechanical testing showed a failure to recover torsional strength in Col1-tk mice, in contrast to WT. Our data indicates that suppression of proliferating osteoblast-lineage cells for at least 2 weeks after fracture blunts the formation and remodeling of a mineralized callus leading to a functional nonunion. We propose this as a new murine model of atrophic nonunion. © 2021 American Society for Bone and Mineral Research (ASBMR).     

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.     

经皮自体骨髓移植治疗骨折延迟愈合及不愈合

目的 探讨经皮自体骨髓移植治疗骨折延迟愈合、不愈合的疗效。方法 对11例骨折不愈合、4例延迟愈合患者,在C臂X线机透视下将所取自体红骨髓注射至骨折延迟愈合、不愈合部位。定期摄X线片复查。结果 12例获得愈合,愈合时间3～11个月。3例未愈合,未见异位骨化等并发症。结论 自体骨髓移植,是临床上治疗骨折延迟愈合及不愈合可供选择的方法之一。     

体外冲击波治疗骨不愈的临床观察

目的观察体外冲击波治疗骨不愈的疗效及安全性。方法应用体外震波碎石机所产生的高能震波对25例骨折不愈合病人进行治疗,每月复查X线片检查,了解骨折愈合情况。震波治疗3个月后如骨折处无明显骨痂生长,则再行一次震波治疗。结果震波治疗后,骨痂出现时间为4～11周,平均9周。25例中,5例无效;20例有较明显骨痂生长,其中18例最终骨折完全愈合,骨折愈合时间为10～21周,平均14周。治疗总有效率为80%,治愈率为72%。震波治疗后未观察到肢体神经血管损伤等并发症。结论体外冲击波治疗骨不愈疗效可靠、创伤小、方法简单安全,可作为治疗骨不愈的首选方法。     

Repair of tibial nonunions and bone defects with the Taylor Spatial Frame

OBJECTIVE: To investigate the outcomes of tibial nonunions and bone defects treated with the Taylor Spatial Frame (TSF) using the Ilizarov method. DESIGN: Retrospective. SETTING: Limb Lengthening and Deformity Service at an academic medical center. PATIENTS: Thirty-eight consecutive patients with 38 tibial nonunions were treated with the TSF. There were 23 patients with bone defects (average 5.9 cm) and 22 patients with leg-length discrepancy (LLD) (average 3.1 cm) resulting in an average longitudinal deficiency (sum of bone defect and LLD) of 6.5 cm in 31 patients (1-16). The average number of previous surgeries was 4 (0-20). At the time of surgery, 19 (50%) nonunions were diagnosed as infected. INTERVENTION: All patients underwent repair of the nonunion and application of a TSF. Patients with bone loss were additionally treated with lengthening. Infected nonunions were treated with 6 weeks of culture-specific antibiotics. MAIN OUTCOME MEASUREMENTS: Bony union, time in frame, eradication of infection, leg-length discrepancy, deformity, Short Form-36 (SF-36) scores, American Academy of Orthopaedic Surgeons (AAOS) lower-limb scores, and Association for the Study of the Method of Ilizarov (ASAMI) bone and functional results. RESULTS: Bony union was achieved after the initial treatment in 27 (71%) patients. The presence of bone infection correlated with initial failure and persistent nonunion (P=0.03). The 11 persistent nonunions were re-treated with TSF reapplication in 4, intramedullary rodding in 3, plate fixation in 2, and amputation in 2 patients. This resulted in final bony union in 36 (95%) patients. The average LLD was 1.8 cm (0-6.8) (SD 2). Alignment with deformity less than 5 degrees was achieved in 32 patients and alignment between 6 degrees and 10 degrees was achieved in 4 patients. Significant improvement of Short Form-36 (SF-36) scores was noted in physical role (P=0.03) and physical function (P=0.001). AAOS lower-limb module scores significantly improved from 56 to 82 (P<0.001). ASAMI bone and functional outcomes were excellent or good in 36 and 34 patients, respectively. The number of previous surgeries correlated inversely with the ASAMI bone (P=0.003) and functional (P=0.001) scores. CONCLUSIONS: One can comprehensively approach tibial nonunions with the TSF. This is particularly useful in the setting of stiff hypertrophic nonunion, infection, bone loss, LLD, and poor soft-tissue envelope. Infected nonunions have a higher risk of failure than noninfected cases. Treatment after fewer failed surgeries will lead to a better outcome. Internal fixation can be used to salvage initial failures.     

更换髓内钉与保留髓内钉附加钢板治疗髓内钉固定后股骨肥大性骨不连

 目的 探讨更换髓内钉与保留髓内钉附加钢板治疗髓内钉固定后股骨肥大性骨不连的手术适应证。方法 1998年 4月至 2009年 6月收治髓内钉固定后股骨肥大性骨不连患者 20例,11例更换髓内钉,9例保留髓内钉附加钢板固定。两组患者性别、年龄、合并伤、骨折部位、骨折类型的差异无统计学意义。通过术后 1、2、3、4、6、12个月及以后每年 1次影像学和临床功能随访,观察骨痂生长情况和患肢功能。结果两组随访时间、手术时间、术中出血量、术后引流血量、住院时间、影像学愈合时间、临床愈合时间和美国矫形外科医师学会下肢功能评分均无统计学差异。更换髓内钉组住院费用多于保留髓内钉附加钢板组(t'=16.4,P=0.013)。更换髓内钉组 4例未获得骨性愈合,其中 2例为股骨下 1/3骨折,1例为狭部 B型骨折,1例为 32-A3型骨折。再次手术,其中 3例采用髂骨植骨保留髓内钉附加钢板固定,1例行动力化。保留髓内钉附加钢板组全部获得骨性愈合。两组愈合率的差异有统计学意义(χ²= 6.01,P=0.008)。结论 更换髓内钉只适用于股骨狭部肥大性骨不连。对干骺端骨不连、伴有大蝶形游离骨块、骨缺损及更换髓内钉失败病例可采用保留髓内钉附加钢板固定。     

经皮自体红骨髓植入治疗胫骨中下段骨折延迟愈合及不愈合

目的 探讨经皮自体红骨髓植入治疗胫骨中下段骨折延迟愈合及不愈合的疗效.方法 对胫骨中下段骨折延迟愈合18例、骨折不愈合5例患者,将自体红骨髓植入至骨折断端,定期摄X线片复查.结果 23例均获得随访,时间4～16个月,患者骨折均愈合,愈合时间3～12个月,未见骨折畸形愈合、异位骨化及感染等并发症.结论 经皮自体红骨髓植入治疗胫骨中下段骨折延迟愈合及不愈合是一种有效、安全、简易、实用的方法.     

Qualitative and quantitative analysis of orthotopic bone regeneration by marrow

A rat model of a femoral segmental defect was used to specifically test the hypothesis that autogenous marrow has the osteogenic capability to heal a bone defect. The variables analyzed included the ratio of the marrow volume to the defect, implantation of live or dead marrow, and remodeling of established nonunions by implantation of live marrow. The uniqueness of this model allows biomechanical evaluation of the new bone formed by the implant. When live marrow was implanted, woven bone formed at 3 weeks, progressing to early lamellar bone at 6 weeks, with subsequent remodeling for as long as 12 weeks in a volumetric fashion (p < 0.05). Bone marrow, when placed in a fresh femoral defect and given in sufficient amounts, produced a rate of union comparable with that of autologous bone grafts. Mature lamellar bone formed by marrow was evaluated biomechanically: the results were statistically comparable with those of cancellous bone grafts at 12 weeks. Significant bone formation occurred when marrow was percutaneously injected in femoral nonunions, although union and remodeling did not take place in this rat model. Implantation of dead marrow resulted in rare cellular infiltration and minimal bone formation in a manner comparable with that of autogenous cancellous bone grafts. These results indicate that bone marrow can lead to structurally functional bone regeneration in an orthotopic location.     

A revised protocol for more clearly classifying a nonunion

Classifying a nonunion solely on the extent of callus formation on a radiograph is insufficient. We have conducted a study with a revised protocol to classify a nonunion more clearly, which uses both radiographic observation and fixation stability. 47 consecutive femoral shaft nonunions were studied using this protocol and 42 nonunions were followed up for at least one year after discovery (range, 1-3 years). 40 nonunions healed after treatment with a union rate of 95.2% (40/42) and a union period of 4.7 plus or minus 0.9 months. The 2 cases of failure were due to implant failure and both healed after reoperation. We recommend this revised protocol as a pretreatment assessment for all nonunions because of its integrity and effectiveness.     

椎间盘镜下异体松质骨复合自体红骨髓植骨治疗骨不连及骨缺损

目的探讨椎间盘镜下异体松质骨复合自体红骨髓植骨治疗四肢长骨干骨不连及骨缺损的临床疗效。方法2003年9月～2006年9月,选择25例创伤后骨不连、骨缺损患者,其中胫骨9例,股骨13例,肱骨3例。骨不连、骨缺损引起须植骨长度1～6 cm,平均2.7 cm,均在椎间盘镜下行瘢痕清除,然后在骨缺损部位植入异体松质骨,再于髂骨取自体红骨髓15～20 ml注入植骨处。结果25例随访12～36个月,平均25个月,切口均一期愈合,无一例发生神经血管损伤症状。除2例术后内固定失败外,余23例骨不连、骨缺损均获骨性愈合,植骨生长良好,骨愈合时间4～9个月,平均5.1月,无感染及再出现骨不连。结论椎间盘镜下异体松质骨复合自体红骨髓植骨治疗骨不连和骨缺损,无须自体髂骨取骨,局部创伤小,血运破坏小,并发症少,骨愈合率高,是一种微创有效的治疗方法。