Fracture healing is a carefully orchestrated process that closely resembles embryonic skeletal development. In 5-10% of all fractures however this process arrests or is impeded, creating a nonunion of bone across the fracture site that severely complicates patient recovery at great economic cost. The pathophysiology of this complication remains largely unknown, although the disruption of specific cytokine signaling pathways, lack of osteogenic cells, vascular disruption, and a suboptimal mechanical environment may all contribute. Smoking, diabetes, and the use of NSAIDs have also demonstrated associations with nonunion. Diagnosis of a nonunion has also proven difficult as radiographic and clinical assessments remain the gold standard but are largely subjective. Following a diagnosis, surgical intervention is typically pursued and augmented with pharmacologic agents and bone stimulators, although evidence for the effectiveness of both remains limited. The future of nonunion understanding and diagnosis are coupled, as current research into the complication’s pathophysiology hopes to elucidate biologic markers of bone healing potentially disrupted in nonunion and detectable in the serum. The use of these markers in addition to the expanded use of validated radiographic scoring present the most promising future diagnostic tools. Advanced grafting techniques and compounds as well as stronger evidence-based pharmacologic augmentation seek to improve outcomes after treatment as well. Overall, this review seeks to provide a comprehensive report of current understandings, diagnostics, and treatments for fracture nonunion and the evidence that supports them, as well as present current and planned future research aimed at developing more efficacious diagnostic and therapeutic modalities.

The following graduate thesis aims to identify important clinical variables, including injury, treatment and healing characteristics, that serve as prognostic indicators for complications in patients with fractures of the tibial shaft. In particular, the complications of focus in this thesis are surgical site infections and nonunion. The three analytical studies comprising this thesis were derived from large data sets arising from two randomized controlled trials and an observational cohort study. The first chapter (Open Tibial Fractures: Updated Guidelines for Management) is a published literature review that provides an overall introduction to the thesis. It highlights the paucity of high-quality evidence currently available to inform many of the treatment strategies for patients with open fractures of the tibial shaft. The second chapter (Timing of Irrigation & Debridement and Infection Risk in Severe Open Fractures) is a sub-study of all open fracture patients recruited in the International Orthopaedic Multicenter Study (INORMUS) in Fracture Care. The findings of this study suggest that timing delays to irrigation and debridement for patients with open fracture injuries is associated with an increased risk of surgical site infection. The third and fourth chapters evaluate the association between early healing measures and nonunion in patients with tibial fractures. Specifically, chapter three (Exploring the Association of 3-Month Radiographic Union Score for Tibia Fractures (RUST) with Nonunion in Tibial Shaft Fracture Patients) demonstrates that radiographic healing at three months post-operatively is strongly associated with nonunion at one year. Similarly, chapter four (Nonunion in Patients with Tibial Shaft Fractures—Can Early Functional Status Predict Healing?) demonstrates that functional status at three months post-operatively is also correlated to eventual healing. Both of these studies include patients from the randomized controlled trials, SPRINT (Study to Prospectively Evaluate Reamed Intramedullary Nails in Patients with Tibial Fractures) and FLOW (Fluid Lavage of Open Wounds). / Thesis / Master of Science (MSc) / The enclosed thesis work evaluates outcomes in patients with fractures primarily of the tibial shaft. In particular, the comprised studies assess whether certain characteristics, such as injury factors, treatment variables and early healing progression, are associated with adverse outcomes in these patients. One study found that delays in timing to appropriate surgical care for patients with open fractures (open wound at the site of the fracture) leads to greater risk of infection. Furthermore, two studies found that both the level of radiographic healing and functional status of patients at three months from surgery can help predict if the patient will ultimately heal radiographically at one year from injury. The findings of this thesis work should help orthopaedic care providers identify patients at high risk for infections and nonunions, such that these patients can be closely monitored to minimize the risk of such complications.

<p>During a three-year period (1989-91), all patients living in the county of Uppsala, Sweden, with a radiographically verified fracture of the clavicle were prospectively, consecutively followed (n=245). </p><p>The epidemiological study (I) was restricted to the two first years with 187 fractures in185 patients. The short term study (II) with 6 months follow-up included 222 patients. The long term study (III) with 10 years follow-up included 208 patients. The malunion study (IV) included eight patients and the nonunion study (V) 24 patients all of whom were consecutively operated between 1988-2000.</p><p>Displacement, especially with no bony contact in the initial radiographs, was a statistically significant risk factor for sequelae.</p><p>Comminute fractures, especially if including transversally placed fragments, were associated with a significantly increased risk of remaining symptoms. An increasing number of fragments was also associated with an increased risk of sequelae.</p><p>Patients with remainig symptoms after 6 months were on average older at the time of injury as compared to patients without remaining symptoms. Advancing age was also a significant risk factor for sequelae – specifically pain at rest – still after 10 years.</p><p>There was no difference between gender with respect to the risk of sequelae, except for nonunion.</p><p>Fracture location did not predict outcome, except for more cosmetic defects (middle part).</p><p>Shortening defined as overlapping at the fracture site was a significant risk factor for cosmetic defects after 10 years.</p><p>Patients who experience pain at rest and/or cosmetic defects more than twelve weeks after the fracture have a higher risk for sequelae.</p><p>The radiographic examination should always consist of two projections: the AP (0°) view and the 45° tilted view. Transversally placed fragments are not seen in the 0° view.</p><p>Removal of excessive callus in patients with persistent symptoms even several years after the fracture showed a good outcome. One does not have to stabilize the clavicle when excising the hypertrophic callus.</p><p>Symptomatic clavicular nonunions should be treated with surgery. Reconstruction plate combined with cancellous bone gives a faster and more reliable healing rate than external fixation.</p>

During a three-year period (1989-91), all patients living in the county of Uppsala, Sweden, with a radiographically verified fracture of the clavicle were prospectively, consecutively followed (n=245). The epidemiological study (I) was restricted to the two first years with 187 fractures in185 patients. The short term study (II) with 6 months follow-up included 222 patients. The long term study (III) with 10 years follow-up included 208 patients. The malunion study (IV) included eight patients and the nonunion study (V) 24 patients all of whom were consecutively operated between 1988-2000. Displacement, especially with no bony contact in the initial radiographs, was a statistically significant risk factor for sequelae. Comminute fractures, especially if including transversally placed fragments, were associated with a significantly increased risk of remaining symptoms. An increasing number of fragments was also associated with an increased risk of sequelae. Patients with remainig symptoms after 6 months were on average older at the time of injury as compared to patients without remaining symptoms. Advancing age was also a significant risk factor for sequelae – specifically pain at rest – still after 10 years. There was no difference between gender with respect to the risk of sequelae, except for nonunion. Fracture location did not predict outcome, except for more cosmetic defects (middle part). Shortening defined as overlapping at the fracture site was a significant risk factor for cosmetic defects after 10 years. Patients who experience pain at rest and/or cosmetic defects more than twelve weeks after the fracture have a higher risk for sequelae. The radiographic examination should always consist of two projections: the AP (0°) view and the 45° tilted view. Transversally placed fragments are not seen in the 0° view. Removal of excessive callus in patients with persistent symptoms even several years after the fracture showed a good outcome. One does not have to stabilize the clavicle when excising the hypertrophic callus. Symptomatic clavicular nonunions should be treated with surgery. Reconstruction plate combined with cancellous bone gives a faster and more reliable healing rate than external fixation.

The current gold standard of therapy for treatment of tibial fracture nonunion is iliac crest bone graft. However, this intervention is associated with significant morbidity to the donor site. Research into alternative interventions highlights the role of mesenchymal stem cells (MSCs). MSCs are capable of differentiating into mature, organized osseous tissue as well as recruiting local vascular cells. However, there are few prospective studies demonstrating the therapeutic potential of MSCs in fracture nonunion. The proposed study is a multicenter single-blinded controlled study of MSC application compared to iliac crest bone graft in the setting of fracture nonunion of the tibia. The study subjects will be evaluated at each return to care with mRUST radiographic scoring as well as Short-Form 12 evaluation of general health. These results will be correlated with MSC concentrations as assessed by FACS analysis. The data from this study will help to characterize MSCs as a possible therapeutic intervention in fracture nonunion.

As fraturas de mandíbula são freqüentes e o seu tratamento é por meio de fixação interna rígida. Complicações podem ocorrer após o tratamento das fraturas mandibulares levando a necessidade de reabordagem cirúrgica, havendo poucos estudos a esse respeito na literatura. A proposta deste estudo retrospectivo foi avaliar as características, os possíveis fatores de risco e os tipos de tratamento realizado em pacientes que necessitaram de reabordagem cirúrgica de fraturas de mandíbula tratadas com fixação interna rígida (FIR). Dentre 364 pacientes tratados por fraturas de mandíbula com FIR, houve 17 pacientes (4,7%) que necessitaram de reabordagem cirúrgica, tendo sido incluídos três pacientes provenientes de outros serviços, totalizando 20 casos com necessidade de nova cirurgia. Houve predomínio do gênero masculino, com idade média de 31,4 anos, sendo freqüentes o tabagismo e o etilismo. Foram freqüentes fraturas múltiplas e cominutivas nas regiões de corpo e ângulo mandibular, dente no traço e exposição intraoral da fratura. O tempo de espera para primeira cirurgia foi alto e o acesso extraoral e o sistema de fixação menos rígido 2.0 mm foram freqüentes. As complicações mais comuns foram dor, infecção e mobilidade anormal. Nas culturas bacterianas houve predomínio do Staphylococcus aureus e a imagem mais freqüente foi de reabsorção óssea difusa, seguida por parafuso solto, seqüestro ósseo, traço de fratura visível, fixação solta e placa fraturada. A reabordagem cirúrgica ocorreu em média de 7,5 meses após a primeira cirurgia e constou de remoção dos meios de fixação associada ou não a nova fixação ou ainda a remoção de seqüestro ósseo, sendo que apenas um caso necessitou de refratura. Histologicamente houve predomínio de osteomielite crônica. Os diagnósticos em ordem decrescente foram infecção, pseudoartrose, osteomielite e placa exposta, sendo que muitos pacientes tiveram mais de um diagnóstico. Foi destacada a freqüência de tabagismo e etilismo, fraturas múltiplas e cominutivas na região de corpo e ângulo mandibular, dente no traço, exposição intraoral, tempo de espera alto e acesso extraoral predispondo complicações das fraturas mandibulares e exames de imagem de reabsorção óssea, fixação e parafusos solto e seqüestro ósseo e diagnóstico histológico de osteomielite como característica dos casos requerendo nova cirurgia. / Mandibular fractures are frequent and their treatment is through rigid internal fixation (RIF). Complications can occur after treatment of the mandibular fractures which may require a new surgical procedure, and there are a few studies about that in the literature. The purpose of this retrospective study was to evaluate the characteristics, possible risk factors, and the kinds of treatment did in patients which needed another surgery after treatment of mandibular fracture with RIF. From 364 patients with mandibular fractures treated by RIF, there were 17 patients (4.7%) with need of a new surgery, and 3 patients coming from another city were included, comprising a total of 20 patients who needed a new surgery. There was predominance of the male gender, with a mean age of 31.4 years, being frequent smoking and alcohol abuse. Multiple and comminuted fractures on the body and angle sites, teeth in the fracture line, and intraorally exposed fractures were frequent. Delay time to the first surgery was high, and extraoral approaches and system 2.0mm were predominant. The most common complications were pain, infection and abnormal mobility. In the bacterial culture there was predominance of Staphylococcus aureus, and the most frequent radiographic images were of diffuse bone resorption, loosening of screws, bone sequestration, fracture line visible, loose fixation, and fractured plate. A new surgery occurred with a mean of 7.5 months after the first intervention and comprised plate and screws removal associated or not to a new fixation or bone sequestra removal, and only a case the fracture needed to be osteotomized. Histologically there was predominance of chronic osteomyelitis. The diagnoses in decreasing order were infection, nonunion, osteomyelitis and exposed plate, although many patients had more than one diagnosis. It was evidenced the frequency of smoking and alcohol abuse, multiple and comminuted fracture on the body and angle regions, teeth in the fracture line, intraoral fracture exposition, high delay time and extraoral approaches predisposing complications of the mandibular fractures, and images showing bony resorption, loose hardware and bone sequestra, as well as histological diagnosis of osteomyelitis as characteristic of the cases requiring a new surgery.

As fraturas de mandíbula são freqüentes e o seu tratamento é por meio de fixação interna rígida. Complicações podem ocorrer após o tratamento das fraturas mandibulares levando a necessidade de reabordagem cirúrgica, havendo poucos estudos a esse respeito na literatura. A proposta deste estudo retrospectivo foi avaliar as características, os possíveis fatores de risco e os tipos de tratamento realizado em pacientes que necessitaram de reabordagem cirúrgica de fraturas de mandíbula tratadas com fixação interna rígida (FIR). Dentre 364 pacientes tratados por fraturas de mandíbula com FIR, houve 17 pacientes (4,7%) que necessitaram de reabordagem cirúrgica, tendo sido incluídos três pacientes provenientes de outros serviços, totalizando 20 casos com necessidade de nova cirurgia. Houve predomínio do gênero masculino, com idade média de 31,4 anos, sendo freqüentes o tabagismo e o etilismo. Foram freqüentes fraturas múltiplas e cominutivas nas regiões de corpo e ângulo mandibular, dente no traço e exposição intraoral da fratura. O tempo de espera para primeira cirurgia foi alto e o acesso extraoral e o sistema de fixação menos rígido 2.0 mm foram freqüentes. As complicações mais comuns foram dor, infecção e mobilidade anormal. Nas culturas bacterianas houve predomínio do Staphylococcus aureus e a imagem mais freqüente foi de reabsorção óssea difusa, seguida por parafuso solto, seqüestro ósseo, traço de fratura visível, fixação solta e placa fraturada. A reabordagem cirúrgica ocorreu em média de 7,5 meses após a primeira cirurgia e constou de remoção dos meios de fixação associada ou não a nova fixação ou ainda a remoção de seqüestro ósseo, sendo que apenas um caso necessitou de refratura. Histologicamente houve predomínio de osteomielite crônica. Os diagnósticos em ordem decrescente foram infecção, pseudoartrose, osteomielite e placa exposta, sendo que muitos pacientes tiveram mais de um diagnóstico. Foi destacada a freqüência de tabagismo e etilismo, fraturas múltiplas e cominutivas na região de corpo e ângulo mandibular, dente no traço, exposição intraoral, tempo de espera alto e acesso extraoral predispondo complicações das fraturas mandibulares e exames de imagem de reabsorção óssea, fixação e parafusos solto e seqüestro ósseo e diagnóstico histológico de osteomielite como característica dos casos requerendo nova cirurgia. / Mandibular fractures are frequent and their treatment is through rigid internal fixation (RIF). Complications can occur after treatment of the mandibular fractures which may require a new surgical procedure, and there are a few studies about that in the literature. The purpose of this retrospective study was to evaluate the characteristics, possible risk factors, and the kinds of treatment did in patients which needed another surgery after treatment of mandibular fracture with RIF. From 364 patients with mandibular fractures treated by RIF, there were 17 patients (4.7%) with need of a new surgery, and 3 patients coming from another city were included, comprising a total of 20 patients who needed a new surgery. There was predominance of the male gender, with a mean age of 31.4 years, being frequent smoking and alcohol abuse. Multiple and comminuted fractures on the body and angle sites, teeth in the fracture line, and intraorally exposed fractures were frequent. Delay time to the first surgery was high, and extraoral approaches and system 2.0mm were predominant. The most common complications were pain, infection and abnormal mobility. In the bacterial culture there was predominance of Staphylococcus aureus, and the most frequent radiographic images were of diffuse bone resorption, loosening of screws, bone sequestration, fracture line visible, loose fixation, and fractured plate. A new surgery occurred with a mean of 7.5 months after the first intervention and comprised plate and screws removal associated or not to a new fixation or bone sequestra removal, and only a case the fracture needed to be osteotomized. Histologically there was predominance of chronic osteomyelitis. The diagnoses in decreasing order were infection, nonunion, osteomyelitis and exposed plate, although many patients had more than one diagnosis. It was evidenced the frequency of smoking and alcohol abuse, multiple and comminuted fracture on the body and angle regions, teeth in the fracture line, intraoral fracture exposition, high delay time and extraoral approaches predisposing complications of the mandibular fractures, and images showing bony resorption, loose hardware and bone sequestra, as well as histological diagnosis of osteomyelitis as characteristic of the cases requiring a new surgery.

In the first part of these studies, we have performed standard microsurgical procedures provide a solution for long standing bone and soft tissue defects, even in cases of longstanding osteomyelitis of long bones. When long bony segments are missing, the microvascular bone transfer provides a reliable method. In smaller soft tissue and bone defects, the application of a descending genicular osteomyocutaneous flap provides an option with low donor site morbidity. In the second part, we have focussed on reducing the donor site morbidity and expanded on the application of tissue engineering methods. MSCs derived from bone marrow can be injected percutaneous or be combined with an autologous bony scaffold for treatment of delayed union and nonunion. The outcome of our studies, however, limited in number of patients, clearly showed the possibilities and advantages of this new approach. A multimodality approach is essential, but it can provide promising solutions. Well-established microvascular and modern biotechnology methods will improve patient satisfaction and functional recovery in severe limb trauma, often the result of high-energy motorcycle accidents. / Doctorat en Sciences médicales (Médecine) / info:eu-repo/semantics/nonPublished

No description available.

Αναδρομική μελέτη των 13 ασθενών με σηπτική ψευδάρθρωση κάτω πέρατος μηριαίου που αντιμετωπίστηκαν με ευρύ χειρουργικό καθαρισμό και με τη μέθοδο Ilizarov. Κατά την έναρξη της τελικής αντιμετώπισης όλοι οι ασθενείς είχαν σημαντικό περιορισμό της κίνησης της άρθρωσης του γόνατος. Ο μέσος όρος προηγούμενων χειρουργικών επεμβάσεων ήταν τρεις. Ο μέσος όρος οστικού ελλείμματος ήταν 8.3 εκ. Ο μέσος χρόνος εξωτερικής οστεοσύνθεσης ήταν 309.8 ημέρες. Σύμφωνα με τα κριτήρια Paley σε οκτώ ασθενείς είχαμε άριστο οστικό αποτέλεσμα, ενώ το λειτουργικό αποτέλεσμα ήταν σε τρεις περιπτώσεις άριστο, σε τέσσερις καλό. Πώρωση του κατάγματος, εκρίζωση της λοίμωξης και αποκατάσταση της στηρικτικής ικανότητας του σκέλους επιτεύχθηκε σε όλους τους ασθενείς. Η αύξηση του χρόνου εξωτερικής οστεοσύνθεσης παρατηρήθηκε: 1) η οριστική αντιμετώπιση εφαρμόστηκε 6 μήνες μετά από τον αρχικό τραυματισμό. 2) ο ασθενής υποβλήθηκε σε 4 τουλάχιστον προηγούμενες χειρουργικές επεμβάσεις 3) η αρχική αντιμετώπιση συμπεριλάμβανε ανοικτή ανάταξη και εσωτερική οστεοσύνθεση. Με την μέθοδο Ilizarov επιτυγχάνεται πλήρη εκρίζωση της οστικής λοίμωξης, υψηλό ποσοστό πώρωσης και αποκατάσταση της στηρικτικής ικανότητας του σκέλους. Ωστόσο συχνά η δυσκαμψία του γόνατος και η χωλότητα αποτελούν χρόνιο πρόβλημα για αρκετούς ασθενείς. / We retrospectively reviewed 13 patients with infected nonunion of the distal femur, which had been treated by radical surgical debridement and Ilizarov method. All had severely restricted movement of the knee and a mean of 3.1 previous operations. The mean bone defect was 8.3 cm and no patient was able to bear weight. The mean external fixation time was 309.8 days. According to the Paley’s grading system, eight patients had an excellent bone result and seven excellent and good functional results. Bone union, the ability to bear weight fully, and eradication of infection were achieved in all the patients. The external fixation time was increased when the definitive treatment started six months or more after the initial trauma, the patient had been subjected to more than four previous operations and the initial operation had been ORIF. The treatment of infected defect pseudarthrosis of the distal femur using the Ilizarov device is a salvage procedure, as it offers complete eradication of infection, high union rate and ability for full weight bearing. Nevertheless problems such as, impaired knee joint motion and limping bother the patients permanently.