Salvage of humeral nonunions with onlay bone plate allograft augmentation

Eight women and one man were treated for 10 established diaphyseal humeral nonunions. Six patients sustained fractures in motor vehicle accidents and two patients sustained fractures in a fall. Two of the fractures were open. One patient with multiple myeloma originally was treated conservatively and received local radiation, followed by open reduction and internal plate fixation. The other patients previously were treated with fracture braces, intramedullary nails, dynamic compression plates, or a combination of these techniques. After removal of the surgical hardware and fibrous tissue at the nonunion site, stable fixation was accomplished using a cortical long bone plate allograft (femoral and tibial) or fibular shaft allograft and a dynamic compression plate. All humeral nonunions had united at an average of 2.9 months. Radiographic incorporation of the allograft cortical bone plate and fibular shaft into the host cortex occurred in all but one patient by 3 months. Graft to host junction healing was accomplished by incorporation of the cortical allograft plate into the host cortex, resulting in an increased diameter of the bone. Cortical allograft bone plates and fibular grafts provide structural and probably osteoinductive support to enhance healing of these nonunions.     

Global gene profiling reveals a downregulation of BMP gene expression in experimental atrophic nonunions compared to standard healing fractures.

Nonunion is a challenging problem that may occur following certain bone fractures. However, there has been little investigation of the molecular basis of nonunions. Bone morphogenetic proteins (BMPs) play a significant role in osteogenesis. However, little is known about the expression patterns of BMPs in abnormal bone healing that results in nonunion formation. These facts prompted us to investigate and compare the gene expression patterns of BMPs and their antagonists in standard healing fractures and nonunions using rat experimental models. Standard closed healing fractures and experimental atrophic nonunions produced by periosteal cauterization at the fracture site were created in rat femurs. At postfracture days 3, 7, 10, 14, 21, and 28, total RNA was extracted from the callus of standard healing fracture and fibrous tissue of nonunion (n=4 per each time point and each group). Gene expression of BMPs, BMP antagonists, and other regulatory molecules were studied by methods including Genechip microarray and real-time quantitative RT-PCR. Gene expression of BMP-2, 3, 3B, 4, 6, 7, GDF-5, 7, and BMP antagonists noggin, drm, screlostin, and BAMBI were significantly lower in nonunions compared to standard healing fractures at several time points. Downregulation in expression of osteogenic BMPs may account for the nonunions of fracture. The balance between BMPs and their endogenous antagonists is critical for optimal fracture healing.     

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.     

Differential gene expression and immunolocalization of insulin‐like growth factors and insulin‐like growth factor binding proteins between experimental nonunions and standard healing fractures

Insulin‐like growth factors (IGF‐I/II) are important growth factors in bone, and their actions are regulated by six IGF binding proteins (IGFBPs). However, little is known about their exact functions in fracture healing. The aim of this study was to compare the gene expression and immunolocalization of IGFs and IGFBPs between standard healing fractures and nonunions using rat experimental models. Standard healing fractures and nonunions produced by periosteal cauterization at the fracture site were created in rat femurs. At postfracture days 3, 7, 10, 14, 21, and 28, total RNA was extracted from the callus of the healing fractures and the fibrous tissue of the nonunions, and gene expression were analyzed by real‐time PCR. Additionally, immunolocalization of these proteins was studied by immunohistochemistry at postfracture days 7, 14, and 21. In nonunions, the gene expression of IGF‐I/II and IGFBP‐6 was significantly higher, and that of IGFBP‐5 was significantly lower at several time points. The immunolocalization of IGF‐I/II and IGFBP‐5 was widely distributed in both models. In contrast, that of IGFBP‐6 was barely detected in the fracture callus. In conclusion, our results suggest that IGFs/IGFBPs may have important roles not only in fracture healing but also in nonunion formation. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1820–1826, 2011     

Effect of nerve injury on fracture healing. Callus formation studied in the rat

In an attempt to determine the effects of peripheral nerve lesions on fracture healing, radiographic, histomorphometric and chemical methods were used to evaluate callus formation in tibial fractures of rats with sciatic denervation. Fracture union by bridging external callus was more rapid in denervated limbs than in controls. By contrast, external calluses of denervated fractures were smaller and less dense and contained less collagenous matrix (hydroxyproline) and minerals (calcium, phosphorus) than controls. The RNA/DNA ratio decreased more rapidly in denervated calluses than in controls. Mineralization of collagenous matrix (estimated from the calcium/hydroxyproline ratio) was not affected by denervation.     

Effect of nerve injury on fracture healing: Callus formation studied in the rat

In an attempt to determine the effects of peripheral nerve lesions on fracture healing, radiographic, histomorphometric and chemical methods were used to evaluate callus formation in tibial fractures of rats with sciatic denervation. Fracture union by bridging external callus was more rapid in denervated limbs than in controls. By contrast, external calluses of denervated fractures were smaller and less dense and contained less collagenous matrix (hydroxyproline) and minerals (calcium, phosphorus) than controls. The RNA/DNA ratio decreased more rapidly in denervated calluses than in controls. Mineralization of collagenous matrix (estimated from the calcium/hydroxyproline ratio) was not affected by denervation.     

The neuronal regulation of fracture healing: Effects of sciatic nerve resection in rat tibia

The effect of sciatic nerve resection on tibial fracture healing was studied in rats 25 days post-trauma. To prevent differences in loading between sham-operated and nerve-resected animals the fractured limbs were cast-immobilized. On radiograms 8 of 11 fractures in the sham-operated animals showed very little callus formation in contrast to only 1 of 8 fractures in the group with nerve resection. Measured by single-photon absorptiometry, animals with sciatic nerve resection had a higher bone mineral content than the sham-operated animals. However, the mechanical strength in three-point cantilever bending was not better in the nerve-resected rats, implying a defective organization of the large callus. These results suggest neural regulation plays a role in the type of fracture healing, primary or secondary, and in the amount and quality of the callus.     

Sciatic nerve release following fracture or reconstructive surgery of the acetabulum

BACKGROUND: Sciatic neuropathy associated with acetabular fractures can result in disabling long-term symptoms. The purpose of this retrospective study was to evaluate the effect of sciatic nerve release on sciatic neuropathy associated with acetabular fractures and reconstructive acetabular surgery. METHODS: Between 2000 and 2004, ten patients with sciatic neuropathy associated with an acetabular fracture were treated with release of the sciatic nerve from scar tissue and heterotopic bone. Additional surgical procedures included open reduction and internal fixation of the acetabulum (five patients), removal of hardware and total hip arthroplasty (three patients), and removal of hardware alone (one patient). The average age of the patients was forty-three years. All patients were followed with serial examinations and assessments for a minimum of one year (average, twenty-six months). RESULTS: All patients had partial to complete relief of radicular pain, of diminished sensation, and of paresthesias after the nerve release. Four of seven patients with motor loss and two of five patients with a footdrop demonstrated improvement in function after the nerve release. No patient had evidence of worsening on neurologic examination after the release. CONCLUSIONS: Sciatic nerve release during reconstructive acetabular surgery can decrease the sensory symptoms of preoperative sciatic neuropathy associated with a previous acetabular fracture. Motor symptoms, however, are less likely to resolve following nerve release.     

The effects of tibial fracture and Ilizarov osteosynthesis on the structural reorganization of sciatic and tibial nerves during the bone consolidation phase and after fixator removal

Reactive and adaptive changes in mechanically uninjured nerves during fracture healing have not been studied previously although the status of innervation is important for bone union and functional recovery. This study explores whether subclinical nerve fibre degeneration occurs in mechanically uninjured nerves in an animal fracture model and to quantify its extent and functional significance. Twenty-four dogs were deeply anaesthetized and subjected to experimental tibial shaft fracture and Ilizarov osteosynthesis. Before fracture and during the experiment, electromyography was performed. In 7, 14, 20, 35–37 and 50 days of fixation and 30, 60–90 and 120 days after fixator removal, the dogs were euthanized. Samples from sciatic, peroneal and tibial nerves were processed for semithin section histology and morphometry. On the 37th postoperative day, M-response amplitudes in leg muscles were 70 % lower than preoperative ones. After fixator removal, these increased but were not restored to normal values. There were no signs of nerve injuries from bone fragments or wires from the fixator. The incidence of degenerated myelin fibres (MFs) was less than 12 %. Reorganization of Remak bundles (Group C nerve fibres—principally sensory) led to a temporal increase in numerical nerve fibre densities. Besides axonal atrophy, the peroneal nerve was characterized with demyelination–remyelination, while tibial nerve with hypermyelination. There were changes in endoneural vessel densities. In spite of minor acute MF degeneration, sustained axonal atrophy, dismyelination and retrograde changes did not resolve until 120 days after fracture healing. Correlations of morphometric parameters of degenerated MF with M-response amplitudes from electromyography underlie the subclinical neurologic changes in functional outcomes after tibial fractures even when nerves are mechanically uninjured.     

Development of an atrophic nonunion model and comparison to a closed healing fracture in rat femur.

Although most fractures heal, some fail to heal and become nonunions. Many animal models have been developed to study problems of fracture healing. The majority of nonunion models have involved segmental bone defects, but this may not adequately represent the biologic condition in which nonunions clinically develop. The objective of the present study is to develop a nonunion model that better simulates the clinical situation in which there is soft tissue damage including periosteal disruption and to compare this model to a standard closed fracture model utilizing identical fracture stabilization, providing a similar mechanical environment. A total of 96 three month old Long Evans rats were utilized. A 1.25 mm diameter K-wire was inserted into the femur in a retrograde fashion, and a mid-diaphyseal closed transverse fracture was created using a standard three-point bending device. To create a nonunion, 48 of the rats received additional surgery to the fractured femur. The fracture site was exposed and 2 mm of the periosteum was cauterized on each side of the fracture. Fracture healing was evaluated with serial radiographs every two weeks. Animals were maintained for intervals of two, four, six or eight weeks after surgery. Specimens from each time interval were subjected to biomechanical and histological evaluation. None of the cauterized fractures healed throughout the eight weeks experimental duration. The radiographical appearance of nonunion models was atrophic. This investigation showed pronounced differences between the experimental nonunions and standard closed fractures both histologically and biomechanically. In conclusion, we have developed a reproducible atrophic nonunion model in the rat femur that simulates the clinical condition in which there is periosteal disruption but no bone defect.     

Strut allografts for failed treatment of periprosthetic femoral fractures: Good outcome in 13 patients

Strut allografts are not recommended after a femoral shaft exposure, because they may endanger the femoral blood supply. Up till now, we have seen no clinical reports on this problem. We treated 13 consecutive patients with very large anteromedial and anterolateral femoral strut allografts to restabilize periprosthetic fractures which had become loose after a previous attempt at surgical fixation (Vancouver type B fractures with severe bone loss). In 8 cases, the stem was revised in conjunction with the use of strut allografts and in 5 cases, strut allografts alone were used. All refractures and nonunions healed without further treatment. At a mean follow-up of 3 (1.2-7) years, the mean Harris Hip Score was 78 (65-92). All strut grafts showed ingrowth with augmentation of periprosthetic bone on the radiographs. There were 3 complications, 1 nonprogressive subsidence of a revision stem (fibrous stable), 1 deep hematoma and 1 partial lesion of the sciatic nerve. In this series, strut grafts gave reliable healing with augmentation of the host bone stock despite previous femoral exposure, severe bone loss, adverse type of fracture, and persistent instability at the index operation.     

Strut allografts for failed treatment of periprosthetic femoral fractures: good outcome in 13 patients

Strut allografts are not recommended after a femoral shaft exposure, because they may endanger the femoral blood supply. Up till now, we have seen no clinical reports on this problem. We treated 13 consecutive patients with very large anteromedial and anterolateral femoral strut allografts to restabilize periprosthetic fractures which had become loose after a previous attempt at surgical fixation (Vancouver type B fractures with severe bone loss). In 8 cases, the stem was revised in conjunction with the use of strut allografts and in 5 cases, strut allografts alone were used. All refractures and nonunions healed without further treatment. At a mean follow-up of 3 (1.2-7) years, the mean Harris Hip Score was 78 (65-92). All strut grafts showed ingrowth with augmentation of periprosthetic bone on the radiographs. There were 3 complications, 1 nonprogressive subsidence of a revision stem (fibrous stable), 1 deep hematoma and 1 partial lesion of the sciatic nerve. In this series, strut grafts gave reliable healing with augmentation of the host bone stock despite previous femoral exposure, severe bone loss, adverse type of fracture, and persistent instability at the index operation.     

Treatment of delayed and nonunited fractures and osteotomies with pulsed electromagnetic field in children and adolescents

Nonunion of fractures or osteotomies in the pediatric population is rare. The gold standard for the treatment of nonunions involves harvesting autologous iliac crest bone graft and sometimes internal fixation, which are invasive procedures. The purpose of this study was to evaluate the effectiveness of pulsed electromagnetic field on a non-united fracture or osteotomy in the pediatric population. A retrospective study was performed on all patients at the authors' institution who used pulsed electromagnetic field as part of their treatment for nonunion or delayed union. Success of the initial nonunion treatment was defined as complete union of the fracture or osteotomy site. Two types of treatment were administered once delayed bone healing was identified: pulsed electromagnetic field alone or pulsed electromagnetic field plus an adjunct treatment. Twenty-one patients were included; 8 osteotomies and 14 fractures developed a nonunion. Average patient age was 11.7 years. Average age for patients who healed with the initial treatment was 10.7 years, whereas nonhealers had an average age of 14 years. Eighty-nine percent of osteotomy nonunions healed with their first management. Fifty-seven percent of fracture nonunions healed at the first attempt. The use of pulsed electromagnetic field is a good option for the initial treatment of pediatric nonunions, especially for patients who develop nonunions secondary to osteotomies. Adding bone marrow aspiration improves the outcomes and is minimally invasive compared with autologous iliac crest bone graft, with no complications.     

Complications after titanium elastic nailing of pediatric tibial fractures

A retrospective review of 60 diaphyseal tibia fractures (31 closed and 29 open fractures) treated with flexible intramedullary fixation was conducted. All charts and radiographs were reviewed. Children ranged in age from 5.1 to 17 years. Fifty patients with 51 fractures were followed up until union and comprised the study group. The mean follow-up period for these 50 patients was 79 weeks. Forty-five fractures achieved bony union within 18 weeks (mean, 8 weeks). Five patients (11%) had delayed healing (3 had delayed unions that ultimately healed with casting or observation, and 2 had nonunions that required secondary procedures to achieve union [1 patient underwent a fibular osteotomy, and 1 underwent exchange nailing with a reamed tibial nail]). These 5 fractures ultimately healed, with a mean time to union of 41 weeks. Patients with delayed healing tended to be older (mean age, 14.1 years) versus the study population as a whole (mean age, 11.7 years). In addition to delayed union, other complications were observed in the study population. One patient healed with malunion (13-degree valgus), requiring corrective osteotomy. One patient with a grade II open fracture was diagnosed with osteomyelitis at the fracture site after attaining bony union. Two patients developed nail migration through the skin, requiring modification or nail removal.The fixation of pediatric diaphyseal tibia fractures with titanium elastic nails is effective but has a substantial rate of delayed healing, particularly in older patients.     

Screw fixation without bone grafting for scaphoid fracture nonunion

IntroductionWe previously reported the classification of the scaphoid fracture nonunions as linear, cystic, and sclerotic or displaced types based on radiographic findings. We have been treating the linear and cystic type fractures via screw fixation without bone grafting and the sclerotic or displaced type fractures via screw fixation with bone grafting. In this retrospective study, we report the treatment outcomes of the linear and cystic types of scaphoid fracture nonunions.MethodsNineteen patients with linear and cystic type scaphoid fracture nonunions were included. Two patients had linear type and 17 had cystic type fractures. All the patients were male, their mean age was 29.2 years. All patients were treated with screw fixation alone by a single surgeon.ResultsBone union was achieved in 17 cases. The mean time to bone union was 3.7 months. Bone union was not achieved in one case of linear type and one case of cystic type fracture. The former was thought to be due to misdiagnosis of displaced type as linear type fracture; however, no obvious reason could be found for the latter.DiscussionScrew fixation alone could help achieve bone union in linear type scaphoid fracture nonunions. However, if the type of the fracture is difficult to diagnose based on plain radiography, evaluation using computed tomography should be performed. The cystic type fractures may need to be subclassified according to the location or size of the cyst as well as the viability of the proximal bone fragment.     

Electrical treatment of non-united fractures

The semi-invasive technique for electrical stimulation of bone healing developed by Brighton et al. (1977) was used in 23 patients with nonunited fractures of the tibia (14 cases), humerus (4 cases), scaphoid, femur and fibula as well as one failed arthrodesis of the ankle. The fractures were clinically not healed and not operated on within a minimum of 6 months. The mean period from fracture to treatment was 18 months. Electrical stimulation led to solid bone healing in 10 cases. Two deep infections occurred during the treatment. Of 13 cases that did not unite, a great range of motion in the nonunion area was an obvious cause of failure in seven cases. The results in this series cannot compete with those of bone graft surgery for nonunions.     

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.     

Electrical treatment of non-united fractures

The semi-invasive technique for electrical stimulation of bone healing developed by Brighton et al. (1977) was used in 23 patients with nonunited fractures of the tibia (14 cases), humerus (4 cases), scaphoid, femur and fibula as well as one failed arthrodesis of the ankle. The fractures were clinically not healed and not operated on within a minimum of 6 months. The mean period from fracture to treatment was 18 months. Electrical stimulation led to solid bone healing in 10 cases. Two deep infections occurred during the treatment. Of 13 cases that did not unite, a great range of motion in the nonunion area was an obvious cause of failure in seven cases. The results in this series cannot compete with those of bone graft surgery for nonunions.     

Extrakorporale Stoßwellentherapie

Extracorporeal shock wave therapy (ESWT) has been established as a unique treatment option for soft tissue and bone pathologies. Typical indications include plantar fasciitis, tendinosis calcarea, and tennis elbow, as well as bone pathologies such as nonunions. Regarding the efficacy of ESWT in acute fractures, the literature is herein reviewed. Significant and effective acceleration of fracture and osteotomy healing as well as improvement of biomechanical bone properties by ESWT has been demonstrated in most of the relevant published animal studies. Thus, variable and noncomparable treatment parameters have been applied, and an optimized treatment protocol still must be established. Clinical data are limited to one prospective randomized trial, which demonstrated significant stimulation of healing of long bone fractures after ESWT was applied to the fracture site immediately after open reduction and internal fixation. Additional studies are required to corroborate the effectiveness of ESWT in acute fractures. Although the effectiveness of ESWT has been postulated in a myriad of trials investigating nonunions, published data are not sufficient to allow the recommendation of shock wave treatment for acute fractures also.     

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。