Percutaneous grafting with bone marrow autologous concentrate for open tibia fractures: analysis of forty three cases and literature review

Purpose

Tibial fractures are the most common lower limb fractures. Some criteria such as open fractures and increasing open stage are known to be associated with high delayed union and pseudarthrosis rate. In cases of delayed or nonunion, classical treatment is autologous cancelous bone graft which is associated with high morbidity rate. The ideal treatment would be a percutaneous harvesting and grafting technique. As bone marrow autologous concentrate (BMAC) presents both advantages, we evaluated this technique from 2002 to 2007.

Methods

This was a retrospective study of 43 cases of open tibial fractures with initial surgical treatment. The criteria of inclusion were open fracture and nonunion, delayed union or suspicion of delayed union.

Results

In 23 cases (53.5 %) BMAC was successful. The success group had received significantly more CFU-F than the failure group (469 vs 153.10³, p?=?0.013). A threshold of 360.10³ CFU-F grafted could be established over which there was 100 % success. BMAC done before 110 days after fracture had 47 % success and BMAC done since 110 days after fracture had 73 % success. BMAC success rate decreased with increasing initial fracture skin open stage. There was no BMAC success in cases of a fracture with a remaining gap of more than 4 mm. We had no complications with the technique at the iliac harvesting zone and tibia injection point.

Conclusion

BMAC is a technique that should be considered as one of the different alternatives for management of long-bone delayed and nonunion because of its effectiveness, low complication rate, preservation of bone stock and low cost.     

External fixation by Hoffmann-Vidal-Adrey osteotaxis for severe tibial fractures. Treatment scheme and technical criticism

In addition to the many advantages of external fixation, e.g., Hoffmann's osteotaxis technique, in the treatment of severe, open tibial fractures (grades II and III), some disadvantages result from both technical factors and the nature of the bone injury. Risk of delayed union or nonunion and secondary bone atrophy is due not only to the severity, comminution, soft tissue injury, and/or infection of the fracture site but also to the prolonged use of the external fixation equipment and the long nonweight-bearing time. In addition, a small distraction between the main fragments is often present after an otherwise successful reduction of an unstable comminuted fracture. The use of compression rods in an attempt to remove the distraction often leads to loss of the reduction result (sliding effect). The necessary compression effect between the tibial fragments in early weight-bearing is further prevented by the usual early union of the fibular fracture, which enhances the danger of delayed union or nonunion in the tibia, especially in older persons. To prevent the ossification disturbances mentioned, the authors treated 79 patients during the period from 1971 to 1978 by osteotaxis consisting of (1) a relatively short fixation time (less than or equal to 10 weeks); (2) correspondingly early graded weight-bearing in a cast; and (3) prophylactic fibulectomy in patients with the distraction phenomenon of comminuted tibial fractures. These patients have been followed up for an average of more than five years. This treatment scheme used during the early phase of treatment is often effective in producing union of tibial fractures without bone grafting. However, during later phases closed intramedullary nailing (Küntscher nail) can be used as a reliable method to treat the few severe cases that are resistant to the measures mentioned.     

Transverse debridement and acute shortening followed by distraction histogenesis in the treatment of open tibial fractures with bone and soft tissue loss

This retrospective case series evaluates the technique of transverse debridement, acute shortening and subsequent distraction histogenesis in the management of open tibial fractures with bone and soft tissue loss, thereby avoiding the need for a soft tissue flap to cover the wound. Thirty-one patients with Gustilo grade III open tibial fractures between 2001 and 2011 were initially managed with transverse wound extensions, debridement and shortening to provide bony apposition and allowing primary wound closure without tension, or coverage with mobilization of soft tissue and split skin graft. Temporary monolateral external fixation was used to allow soft tissues resuscitation, followed by Ilizarov frame for definitive fracture stabilization. Leg length discrepancy was corrected by corticotomy and distraction histogenesis. Union was evaluated radiologically and clinically. Patients’ mean age was 37.3 years (18.3–59.3). Mean bone defect was 3.2 cm (1–8 cm). Mean time to union was 40.1 weeks (12.6–80.7 weeks), and median frame index was 75 days/cm. Median lengthening index (time in frame after corticotomy for lengthening) was 63 days/cm. Mean clinic follow-up was 79 weeks (23–174). Six patients had a total of seven complications. Four patients re-fractured after frame removal, one of whom required a second frame. Two patients required a second frame for correction of residual deformity, and one patient developed a stiff non-union which united following a second frame. There were no cases of deep infection. Acute shortening followed by distraction histogenesis is a safe method for the acute treatment of open tibial fractures with bone and soft tissue loss. This method also avoids the cost, logistical issues and morbidity associated with the use of local or free-tissue transfer flaps and has a low rate of serious complications despite the injury severity.     

TGF-β1 als pathophysiologischer Faktor bei der Frakturheilung

AIM: TGF-beta1 is an important local and systemic regulatory molecule during fracture healing. Various authors have shown differences in the systemic levels of TGF-beta1 over the time taken for bone healing in distraction osteogenesis and osteotomies. Previous studies have shown characteristic differences in the physiological levels of growth factors between normal fracture healing and delayed fracture union. The aim of the present study was to evaluate possible differences in sera levels of patients with normal and delayed union fracture healing. METHODS: Patients with long bone shaft fractures were recruited prospectively. Peripheral blood samples were collected over a period of 1 year using a standardized time schedule. At the end of the individual's investigation period, TGF-beta1 levels were determined. To achieve a homogeneous collective of patients, only those with a maximum of two fractures were included in the study. After matching for four criteria, we compared patients with normal fracture healing to patients with delayed unions. The fact of delayed union was accepted in case of failed consolidation 4 months after trauma. RESULTS: During a prospective study period of 1 year, 15 patients with normal fracture healing could be compared to 15 patients suffering from delayed union. By determining the absolute sera levels we found a typical increase of TGF-beta1 up to 2 weeks after fracture in both groups, with a subsequent decrease up to the sixth week after fracture. However, a decline in serum concentration occurred earlier in patients with delayed union, causing significantly lower TGF-beta1 levels in the non-union group 4 weeks after trauma (P=0.00006). CONCLUSION: Even with a relatively small number of patients, we could show a significant difference in serum concentrations of TGF-beta1 between the investigated groups. If these results can be verified within a larger collective, TGF-beta1 could be used as a predictive cytokine for delayed fracture healing.     

Biological fixation of fracture shaft femur in children

The aim of this work was to assess the results of biological fixation of fracture shaft femur in children with locked plates. Twenty-eight fractures in 26 children with closed fractures of the shaft of the femur were managed with biological plating using locked plates bridging the fracture site applied submuscularly through two small incisions above and below the fracture site. The mean age of the patients was 11.2 years; all patients had radiological union within a mean time of 11.9 weeks (8–14 weeks); the average follow-up was 31 months (14–40 months). No patient had frontal or sagittal plane deformity more than 10° or limb length discrepancy more than 1.5 cm. There was no infection, delayed union, nonunion or clinically evident malrotation. A significant positive correlation between the age and the time to healing (p = 0.03) was detected, whereas there was no significant correlation between time to healing and patient sex, fracture level, fracture type, mechanism of injury. Also there was no significant correlation between limb length discrepancy and patient age, sex, fracture level, fracture type, and mechanism of injury. Biological fixation of fractures of the femoral shaft in children with locked plates is a reliable method of fixation with excellent healing potential and fixation mechanics without complications.     

Prediction of the healing potential of closed adult tibial shaft fractures by bone scintigraphy

Fifty unilateral closed adult tibial shaft fractures treated by closed methods were studied prospectively using bone scintigraphy to predict the healing potential of individual fractures. Dynamic and static scintigrams, using 99mtechnetium methylene diphosphonate, were obtained at zero, six, and 12 weeks after fracture. The data were analyzed according to the methods of recent workers in this field. Forty-one fractures united normally at 20 weeks and nine fractures developed delayed union. Analysis of results showed significant differences in uptake ratios, mean net counts, and an osteogenesis index between fractures with normal and delayed union. Of particular value was a ratio of uptake over the fracture site to an adjacent site in the same bone obtained at six weeks. A ratio greater than 2 indicated the potential to heal normally. The findings suggest that a single static scintigram at six weeks is strongly predictive of subsequent healing.     

体外冲击波在促进骨愈合中的应用

目的:观察体外冲击波促进骨折愈合、治疗骨不连的疗效。方法:选取22例外伤性骨折愈合延迟、骨不连患者进行体外冲击波冲击治疗,治疗后每4～6周进行X线片复查,观察骨折愈合情况。首次冲击波治疗12周后如骨折处无明显骨痂形成,则进行第2次冲击波治疗。冲击波能量为0.4mJ/mm2,每次脉冲总数为1600～2400次。结果:22例下肢外伤性骨折愈合延迟及骨不连经体外冲击波治疗后,骨性骨痂形成的时间为4～12周,20例有明显骨痂形成,其中17例在治疗后3～6个月内骨折完全愈合。2例胫骨下段骨折冲击波治疗无效。结论:体外冲击波在治疗骨不连,促进骨折愈合方面效果满意,有广阔的应用前景。     

采用骨端钢板治疗股骨远端骨折58例报告

我院从１９８８年采用骨端钢板治疗股骨远端骨折５８例，髁上骨折２６例，经髁间型骨折３２例，陈旧性骨折２例，开放骨折８例。４７例经６个月至７年的随访，开放骨折仅１例表浅感染，４６例骨折顺利愈合。愈合时间：新鲜骨折平均１１．２周，陈旧骨折平均１４．５周。１例因过早负重钢板折断而延迟愈合。治疗效果：优２９例，良１２例，优良率８７．２％。作者认为，骨端钢板治疗股骨远端骨折，具有手术操作简便，内固定确实的优点，便于早期进行膝关节伸屈练习，疗效满意。     

兔骨折延迟愈合动物模型的建立

目的为骨折延迟愈合的实验研究建立一种客观的动物实验模型。方法选取纯种新西兰大白兔,在后肢胫骨中下段截断,切除远近端各1 cm内外骨膜及黄骨髓,保留断端约1 mm间隙,并且钢板固定。术后4、8、12周后经大体标本、病理组织学及X线检查确定骨折愈合情况。结果大体标本肉眼观察、放射学检查及病理组织学检查均显示术后8周仍未见骨性连接,术后12周才达骨性愈合。结论本实验所建立的动物模型,具有骨折延迟愈合的表现,又未出现骨不连,符合骨折延迟愈合的要求,可以认为是一种可靠而实用的实验性骨折延迟愈合动物模型。     

扩髓带锁髓内钉治疗股骨、胫骨干骨折不愈合、延迟愈合

目的　总结使用扩髓带锁髓内钉治疗股骨、胫骨干骨骨折不愈合、延迟愈合的临床经验。方法　回顾自 1999年 4月～2 0 0 1年 6月使用扩髓带锁髓内钉治疗股骨干、胫骨干骨折不愈合、延迟愈合病人 2 1例 ,其中股骨 8例 ,胫骨 13例 ,钢板固定术后 ,股骨 3例 ,胫骨 6例。普通髓内针股骨 5例。外固定架胫骨 2例。石膏固定胫骨 3例 ,骨牵引股骨 2例。均采用有限切口切开复位顺行扩髓 ,静力锁定加植骨术。结果　随访半年以上 18例 ,骨折均愈合 ,临近关节功能达正常。无感染、断钉等并发症。结论　采用有限切口切开复位、扩髓、静力锁定治疗股骨、胫骨干骨折不愈合、延迟愈合 ,具有骨折稳定性可靠、有利于骨折愈合和早期关节活动的优点 ,是治疗股骨、胫骨干骨折不愈合、延迟愈合的有效方法之一。     

The effect of ultrasound on bone healing across a bone gap,an experimental study of a delayed union model

The aim of the study is to determine whether ultrasound accelerates bone repair across a bone gap. To replicate the clinical situation of bone repair in a severe tibial fracture, such as Gustilo grade three, we designed an experimental model to determine whether ultrasound can promote bone healing in the presence of a bone gap. The effect of ultrasound on bone healing of a tibial bone gap held in an external fixator was studied. 60 New Zealand White rabbits were divided into four groups. In one group of 6 animals, a tibial osteotomy was closed or compressed and studied at six weeks (Comparative Group). In 3 groups of 18 animals each, a tibial bone gap was maintained and was untreated, treated with ultrasound or mock ultrasound (Control Group). The repair of the bone gaps was studied in 3 animals each at 2,4,6,8,10 and 12 weeks. Investigation was by histology, angiography, radiography and densitometry. Three of the 18 untreated group progressed to delayed union, compared with 4 in the ultrasound and 3 in the mock ultrasound group (Control Group). Statistical analysis showed no difference between the three groups. 5 of the 6 closed/compressed osteotomies (Comparative Group) united faster at 6 weeks. The healing pattern of the bone gap groups were similar. We recommend this as a delayed union model. We found no evidence that ultrasound accelerated bone healing, reduced the rate of delayed union or increased callus formation in this model of delayed union. This study simulates delayed union following a compound tibial fracture and has clinical relevance concerning treatment of a delay in union with ultrasound.     

Deformation across the zone of callotasis during loading. radiostereometric analysis in a patient with achondroplasia.

The present study demonstrates that high-resolution radiostereometric analysis (RSA) can be used to assess global longitudinal compressive deformation across the callotasis zone during loading. In an achondroplastic patient operated with bifocal lengthening of the tibia by use of the Ilizarov external fixator, the axial compressive intersegmental strain in the proximal lengthening zone under a load of 71% of body weight was 7.7 mm. The proximal lengthening zone was 51.0 mm, and accordingly the overall linear strain across the callotasis was 15.1%. This large strain value found in distraction osteogenesis 6 weeks after end of distraction is not consistent with classical theory of the magnitude of micromotion needed for adequate stimulation of bone formation in fracture healing. The increased axial displacement did not stimulate bone healing and delayed union was observed. This one single observation does not allow for any conclusions to be drawn about the relationship of strain to fracture healing, but further and refined use of the RSA method will certainly improve our understanding of the role of axial strains in distraction osteogenesis.     

An experimental study on the effects of the plating method for bone fractures--with reference to bone union and bone strength (author's transl)

The plating method for bone fractures is in wide use. The author studied both new bone formation and bone atrophy of the cortex of fracture site after long periods of plating. This study is concerned with the bone strength of the fracture site as influenced by rigid plate fixation, and also with bone union after the removal of the plate. The experimental results, using mature rabbits as subjects, showed the following: X-rays of the bone union at the fracture site treated by the plating method confirmed evident union at 8 weeks after surgery. The bone strength at the region of this union, as tested by the bending method (an Instron Type Testing Machine was used), showed its highest values at 28 weeks after surgery. Yet, this was only 60% of the bone strength as measured at a non-fracture site; it then gradually declined in strength. On the other hand, in the case where the plate had been removed 8 weeks after surgery, bone strength was recovered to the same level as that of non-fracture sites 16 weeks after surgery. In conclusion, rigid plate fixation for a long period may result not only in progressive bone atrophy of the cortex but also in a delayed remodeling of the bone at the region of the bone union. It is, therefore, very important to remove the plate as early as possible once union has been achieved. Careful observation, however, is necessary during the short time between plate removal and the period when bone strength becomes again normal.     

Augmentation of bone healing in delayed and atrophic nonunion of fractures of long bones by partially decalcified bone allograft (decal bone)

Background:

Autograft from iliac crest is considered as gold standard for augmentation of bone healing in delayed and nonunion of fractures. Bone demineralized with 0.6N hydrochloric acid has shown to retain its osteoinductive capacity. We report the outcome of partially decalcified bone allograft (decal bone) in the treatment of delayed union and atrophic nonunions of bones.

Materials and Methods:

Twenty patients with clinicoradiological diagnosis of delayed union or atrophic nonunion of long bone fractures were included in this retrospective study. Patients at extreme of ages (<18 years and >60 years), pathological fractures, metabolic bone diseases, infected nonunion, hypertrophic nonunion and those having systemic illness like diabetes mellitus and on drugs that impair fracture healing were excluded from the study. Decal bone was prepared in the bone bank and maintained in department of orthopedics. Allografting was done in 20 patients of delayed union (9/20) and atrophic nonunion (11/20) of long bone fractures with mean age of 34 years (range 18–55 years). The bones involved were humerus (8/20), tibia (7/20) and femur (5/20). Fourteen patients underwent treatment in the form of internal fixation and allografting and six patients were operated with osteoperiosteal allografting.

Results:

Nineteen patients achieved union in mean time of 14.9 weeks range (range 8–20 weeks). Eight patients had serous discharge from the operative site that subsided in 11 days (range 4–21 days). One patient had pus discharge that required repeat debridement and antibiotics for 6 weeks. The fracture healed in 16 weeks.

Conclusion:

The partially decalcified bone allograft is an effective modality for augmentation of bone healing without complication associated with autograft like donor site morbidity, increased blood loss and increase in the surgical time.     

Effect of osteoporosis on bone mineral density and fracture repair in a rat femoral fracture model

Osteoporosis (OP) is one of the most prevalent bone diseases worldwide with bone fracture the major clinical consequence. The effect of OP on fracture repair is disputed and although it might be expected for fracture repair to be delayed in osteoporotic individuals, a definitive answer to this question still eludes us. The aim of this study was to clarify the effect of osteoporosis in a rodent fracture model. OP was induced in 3‐month‐old rats (n = 53) by ovariectomy (OVX) followed by an externally fixated, mid‐diaphyseal femoral osteotomy at 6 months (OVX group). A further 40 animals underwent a fracture at 6 months (control group). Animals were sacrificed at 1, 2, 4, 6, and 8 weeks postfracture with outcome measures of histology, biomechanical strength testing, pQCT, relative BMD, and motion detection. OVX animals had significantly lower BMD, slower fracture repair (histologically), reduced stiffness in the fractured femora (8 weeks) and strength in the contralateral femora (6 and 8 weeks), increased body weight, and decreased motion. This study has demonstrated that OVX is associated with decrease in BMD (particularly in trabecular bone) and a reduction in the mechanical properties of intact bone and healing fractures. The histological, biomechanical, and radiological measures of union suggest that OVX delayed fracture healing. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:384–393, 2008     

动力化治疗下肢长骨骨折术后延迟愈合的研究进展

下肢长骨骨折术后延迟愈合是骨折术后主要并发症之一。骨折延迟愈合一旦出现，应给予积极的干预措施，避免进一步发展成骨不连。"动力化"技术治疗髓内钉术后骨折延迟愈合，具有微创、高效的特点，临床上已得到广泛运用。锁定加压接骨板（LCP）"动力化"作为一项新技术，有临床证据显示对LCP术后骨折延迟愈合有显著疗效。现就临床上针对下肢长骨干骨折术后延迟愈合的动力化治疗进展作一综述。     

Longitudinal in vivo monitoring of callus remodeling in BMP-7- and Zoledronate-treated fractures

Pharmacological interventions that combine pro-anabolic and anti-catabolic drugs to treat recalcitrant fractures have shown remarkable efficacy in augmenting the regenerative response. Specifically, in rodent models of fracture repair, treatment with BMP-7 and Zoledronate (ZA) has almost uniformally resulted in complete union. However, delayed remodeling may be problematic for ZA-treated fractures. The increase in newly formed bone is substantial but if translated in humans, delayed remodeling may delay functional recovery. Our objective was to determine if, and to what extent, bone morphogenetic protein (BMP) (in synergistically administered BMP-7 + ZA) can modulate the delayed hard callus remodeling caused by ZA. Callus remodeling in BMP-7-only and BMP-7 + ZA-treated osteotomies were monitored using in vivo µCT to follow the progression of healing at 6-week intervals over 24 weeks in an open femoral fracture rat model. None of the groups recovered baseline cortical bone volumes within 24 weeks post-osteotomy. Treatment prolonged the remodeling phase but the kinetics of remodeling appeared to differ between BMP and BMP + ZA groups. However, the mechanical characteristics were largely restored. Callus/bone volumes in BMP-only treated fractures peaked as early as week 3 suggesting that remodeling is stimulated prematurely. However, this rate of remodeling was not maintained as BMP-7 was found to exhibit negligible changes in callus/bone volumes between weeks 6 and 18, whereas declines in callus/bone volumes were present at these time points in the BMP-7 + ZA group. Our findings suggest that inclusion of ZA as an anti-catabolic agent may not be detrimental to the regenerative process despite a prolonged remodeling phase.     

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.     

Low-intensity pulsed ultrasound treatment for postoperative delayed union or nonunion of long bone fractures

Background Postoperative delayed union and nonunion is the most common complication in fracture treatment. Recent studies have shown an accelerating effect of low-intensity pulsed ultrasound (LIPUS) on fracture repair. However, the indications for delayed union and nonunion are not clear. To clarify the factors which influence the effects of LIPUS, the data from a previous prospective multicenter study on LIPUS treatment for postoperative delayed union and nonunion of long bone fractures were reanalyzed. Methods Seventy-two cases of long bone fracture, including those of the femur, tibia, humerus, radius, and ulna, were analyzed. The mean time from the most recent operation to the beginning of LIPUS treatment was 11.5 (3–68) months. The relationship between the background factors and the union rate was analyzed using a logistic regression method. In addition, long bone fractures in an upper extremity or in a lower extremity were analyzed separately. Results The union rate was 75% in all the cases of long bone fracture. There was a significant relationship between the union rate and the period from the most recent operation to the beginning of LIPUS treatment in all cases and in those that had long bone fracture of an upper extremity. There was also a significant relationship between the union rate and the time when a radiological improvement was first observed after the beginning of the treatment in all cases and in those with fractures in a lower extremity. When LIPUS treatment was started within 6 months of the most recent operation, 89.7% of all fractures healed. When an improvement in the radiological changes at the fracture site was observed after 4 months in those cases, then the sensitivity and specificity for union were more than 90%. Conclusions LIPUS treatment should be started within 6 months of the most recent operation. Because LIPUS has been shown to be effective without causing either serious invasiveness or any undue risk to the patient, it may be considered the treatment of first choice for cases of postoperative delayed union or nonunion.