The original Ilizarov frame is a form of circular external fixation in which bone fragments are supported by tensioned fine wires; the wires give the frame a nonlinear axial stiffness which is one of its key qualities. However, as the wires deform plastically in response to loads imposed by functional weight bearing, the stiffness of frame gradually decreases with time. To circumvent this problem the modified Ilizarov frame was conceived in which half pins rather than wires are used for bone support. As fractures managed with Ilizarov fixation tend to unite with little radiographic evidence, monitoring the progression of fracture healing is difficult. The study described in this dissertation had three primary objectives. The first was to investigate the significance of the plastic deformation which occurs in the tensioned fine wires to the long term performance of the original frame. The second was to investigate the biomechanics of the modified frame. The third objective was to conduct a in-vivo feasibility study on the use of fracture axial stiffness measurements as method of monitoring the progression of fracture healing. Plastic deformation of the wires in the original frame readily occurs at moderate load levels because stress concentrations arise at the wire-clamp and wire-bone interfaces. The reduction in frame stiffness is typically 20-30%; re-tensioning only temporarily restores the original frame stiffness. In contrast to the original frame, the modified frame displays a linear stiffness and, as the half pins act as cantilevers, shearing of the bone ends can occur under axial loading. The in-vivo study showed that the technique of relative stiffness measurement, which has been successfully applied to uniaxial fixators, is not directly applicable to Ilizarov fixation. However, it was noted that the standardd eviation of repeatm easurementsd ecreasedw ith the progressiono f healing. It is suggestedt hat this may arise as a result of decreasedm icromovement at the fracture site and might provide a means of monitoring fracture healing itself

No description available.

Introduction Non-union (NU) is a fracture that will not unite. With over one million fractures per annum in the UK long bone non-union has serious social and economical implications. There is little epidemiological data available specifically looking at this NU patient cohort. Studies that are bone specific quote rates of non-union as a proportion of their study group but there is no data quantifying the incidence of NU in the population or per fracture. Studies have highlighted risk factors associated with atrophic non-union including age, diabetes, non-steroidals, and cigarette smoking. There is scientific interest regarding how best to classify non-unions and the role of biological agents in treating them. Aims • To quantify the incidence of non-union in a large population and calculate the risk of non-union per fracture according to age, sex and anatomical distribution. • To assess the causes contributing to non-union and outcomes of treatment in a non-union cohort and validate a new non-union scoring system. • To test the treatment potential of a novel molecule (monobutyrin) and a growth factor in a small animal model of non-union. Method • Using the ICD-10 data from the Scottish population as collected by NHS Scotland the incidence of non-union and fractures were calculated. • A cohort of 100 non-union patients were studied for risk factors associated with their non-union, treatment outcome and to assess a new NU classification system. • A rat model of tibial non-union was used to assess the potential of monobutyrin and BMP-2 in treating non-union in an animal model. Results • Fracture non-union is very rarely found in children (1 in 500 fractures) and occurs in up to 1 in 50 adult fractures. Non-union of a fracture has a significantly higher risk in young adults than the elderly by about 3 fold. Osteoporosis may not be a risk for non-union. The tibia and clavicle are the sites with the greatest potential for fracture non-union. • Non-union is multifactorial in two out of three patients. Biomechanical stability, patient host factors and infection must all be considered in every patient. Occult or unexpected recurrent infection is present in up to 10% of patients. When all factors are considered in treatment the outcome is 95% successful with 88% requiring 2 or less procedures to heal the non-union and only a minority requiring adjuvant graft or biological agents. The proposed new classification system is complex and did not clearly identify those patients who would require adjuvant treatment (eg bone grafting or BMP) or those likely to have unsuccessful non-union treatment. • Monobutyrin and BMP-2 when tested on the small animal non-union model did not improve the success rate of union. Conclusions Non-union affects approximately 1000 people per year in Scotland, this figure is not as high as 5-10% of all fractures. It is associated with fractures in young adults and of the clavicle and tibia, treatment can have a very high success rate without the need for adjuvant biological polytherapy when all contributing factors are considered and managed appropriately. A new non-union classification needs to incorporate the multifactorial aspects of non-union without being too complex to use in everyday clinical situations.

Cancellous bone constitutes much of the volume of bone which makes up axial skeletal sites such as the vertebrae of the spine and the femoral neck. However the increased vascularity of cancellous bone compared with cortical bone means that it is more prone to drug, endocrine and metabolic related effects and therefore these skeletal sites are more prone to the bone condition osteoporosis. With the bone condition osteoporosis increasing in prevalence it is becoming far more important not only for those at risk of having the condition to be diagnosed earlier, but also for the effects of the condition to be better understood. There is a need for the better clinical management of fractures and for therapies and medical practices that will best avoid the low trauma fractures that are seen as a consequence of the condition. This study is in two separate sections, the first constitutes an investigation into the diagnostic abilities of the CUBA Clinical and Sunlight Omnisense quantitative ultrasound systems; and on the other hand an examination of the osteoporotic risk factor questionnaires, Osteoporosis Risk Assessment Instrument (ORAI), Osteoporosis Index of Risk (OSIRIS), Osteoporosis Self-assessment Tool (OST), Patient Body Weight (pBW), Simple Calculated Osteoporosis Risk Estimation (SCORE) and the Study of Osteoporotic Fractures (SOFSURF). The skeletal status was assessed by DXA at the axial skeleton. The aim was to differentiate between the systems that could rationally be used to screen populations to identify those who needed DXA densitometry investigations, on the basis of ability. The second section of the study focused on the biomechanics of cancellous bone, with the initial studies examining the compressive properties of both osteoporotic and osteoarthritic cancellous bone and the effects that the conditions have on the compressive mechanics of the bone. The later section is the first ever study into the K, G and J-integral fracture mechanics of cancellous bone. It used osteoporotic and osteoarthritic cancellous bone from the femoral head of a cohort of ultrasound scanned patients and of some equine vertebral cancellous bone. The study focused on the identification of the dominant independent material variables which affected the compressive and fracture mechanics of cancellous bone, and the differences that were seen between the two different skeletal conditions. In addition to the independent variables, quantitative ultrasound (QUS) scans were performed on the donors of the femoral heads which enabled investigation into QUS’s ability to predict either the compressive or fracture mechanics of bone in-vivo. The study demonstrated that the investigation of the calcaneus using the CUBA clinical system provided the highest level of diagnostic accuracy (AUC: 0.755 - 0.95), followed by the questionnaires, of which the OSIRIS questionnaire was the best performer (AUC: 0.74 – 0.866), and lastly the Sunlight Omnisense results. The best option for the prediction of the lowest feasible DXA T-score was a combination of the CUBA Clinical results, the individual’s weight and the OSIRIS questionnaire (r2 = 45.5%), with potential minor, but significant, support also added by the OST and SOFSURF questionnaires (r2 = 46.8%). The compressive testing demonstrated that osteoporotic and osteoarthritic bone both performed differently with respect to the apparent density, with the osteoporotic bone adhering to the previously published power function relationships, but with the osteoarthritic bone having lower power functions. The stress intensity factor for plane strain testing (KQ or KC) and the critical strain energy release rate results were both influenced primarily by the apparent density with the K values obeying a power relationship to the power of 1.5 and G a relationship to the power 2. However, both the composition and integrity of the collagen network, (demonstrated by collagen cross-link analysis), played roles in the explanation of the fracture mechanics results. The J-integral results were distinctly different to those of the K and G results with regard to their dependence on composition and it is hypothesised that this is due to the structure of the bone having more dominant effects than the apparent density. In conclusion, the fracture mechanics of cancellous bone are contributed to by a complex combination of a number of variables, but with apparent density dominating the K and G fracture mechanics to a power function of between 1 and 2. Currently available QUS systems demonstrated an ability to relate to the Young’s modulus and strength but also, in this study, to the fracture mechanics variables of the cancellous bone from the hip. This relationship is a profound outcome which may help the clinical management of the condition and the fractures when they occur. The dependence on fracture mechanic variables points to a clear causal relationship between the bone fracture parameters and bone condition as underlying factors of osteoporotic fractures.

A critical review of studies related to the modelling of the human locomotor system is given. Kinematic and dynamic modelling and analysis of the pelvis-leg apparatus as an ensemble of four rigid body segments are described. Experiments were performed on two patients with custom-made instrumented massive proximal femoral prostheses implanted after tumour resection. Telemetered axial forces transmitted along the prostheses, together with kinematic, force plate and electromyographic data, were recorded synchronously during level walking, single and double leg stance, and isometric tests of the hip muscles. A sagittal plane model of the locomotor system, with an anatomical model of the knee joint, was developed from an existing model and used for a comparative study of methods for the calculation of the internal forces. A three-dimensional computer graphics-based animated model of the locomotor system was developed, with the hip as a ball-and-socket joint, the knee as a parallel spatial mechanism and the ankle as a two-hinge complex. Thirty-four muscles or muscle groups were included. A method for the determination of the orientation of multi-joint systems from surface markers was developed to take account of measurement errors including skin movement artefacts. Both the 2D and 3D models of the locomotor system were evaluated and validated quantitatively with the telemetered femoral axial forces. It is concluded that (a) a significant part of the bending moments along limbs are transmitted by a combination of tensile forces in muscles and compressive forces in bones so that moments transmitted by the bones are much less than the limb moments, (b) bi-articular muscles play a major role in modulating forces in bones, (c) appropriate simulation of muscle forces is important in experimental or theoretical studies of load transmission along bones, (d) computer graphics-based modelling and animation are important tools in bridging the gap between clinical users and biomechanists.

Η διαδικασία πώρωσης καταγμάτων των οστών συμπεριλαμβάνει την ενεργοποίηση και αλληλεπίδραση διαφόρων κυττάρων, που ρυθμίζονται από βιοχημικά και μηχανικά σήματα. Στην παρούσα διπλωματική εργασία μελετάται το μαθηματικό μοντέλο πώρωσης καταγμάτων οστών, συμπεριλαμβανομένου μόνο των βιοχημικών ερεθισμάτων. Το μοντέλο αυτό, που αναπτύχθηκε αρχικά από τους Geris L. et al. (2008), περιλαμβάνει μία σειρά μερικών μη γραμμικών διαφορικών εξισώσεων που περιγράφουν την χωροχρονική εξέλιξη των συγκεντρώσεων και των πυκνοτήτων των κυτταρικών τύπων, των τύπων εξωκυττάριας θεμέλιας ουσίας και των αυξητικών παραγόντων που συμμετέχουν στη διαδικασία πώρωσης. Η προσομοίωση του μαθηματικού μοντέλου πώρωσης οστών έγινε μέσω υπολογιστικού κώδικα πεπερασμένων όγκων στο Matlab. Ιδιαίτερη έμφαση δίνεται στην διαδικασία της αγγειογένεσης που λαμβάνει χώρα κατά την πώρωση των καταγμάτων και αποτελεί σημαντικό παράγοντα για την αποκατάσταση των οστών και την πλήρη επαναφορά τους στην αρχική κατάσταση. Για την καλύτερη κατανόηση των διαδικασιών αγγειογένεσης, εκτός από την μελέτη του μαθηματικού μοντέλου της πώρωσης των οστών, πραγματοποιήθηκε μελέτη των βιολογικών διαδικασιών επούλωσης δερματικής πληγής και προσομοίωση με υπολογιστικό κώδικα στο Matlab του απλοποιημένου μαθηματικού μοντέλου της αγγειογένεσης στην επούλωση δερματικών πληγών. / The process of fracture healing involves the action and interaction of many cells, regulated by biochemical and mechanical signals. This postgraduate dissertation studies a mathematical bone fracture healing model for the case of normal fracture healing including only the biochemical factors (a bioregulatory model). The mathematical model, which was originally established by Geris L. et al. (2008), consists of a system of nonlinear partial differential equations describing the spatiotemporal evolution of concentrations and densities of the cell types, extracellular matrix types and growth factors indispensable to the healing process. The simulation of mathematical model was held by a computational finite volume code in Matlab. Particular emphasis is given to the process of angiogenesis, which occurs during fracture healing and is a key factor for bone repair and restore of the original state. For a better understanding of angiogenesis processes, a study in biological processes for dermal wound healing was held and a simulation of a simplified mathematical model of angiogenesis in healing dermal wounds by a computational code in Matlab.

Age-related bone fractures are usually painful and have highly negative effects on a geriatric patient's functional status, quality of life, and survival. Currently, there are few analgesic therapies that fully control bone fracture pain in the elderly without significant unwanted side effects. However, another way of controlling age-related fracture pain would be to preemptively administer an osteo-anabolic agent to geriatric patients with high risk of fracture, so as to build new cortical bone and prevent the fracture from occurring. A major question, however, is whether an osteo-anabolic agent can stimulate the proliferation of osteogenic cells and build significant amounts of new cortical bone in light of the decreased number and responsiveness of osteogenic cells in aging bone. To explore this question, geriatric and young mice, 20 and 4 months old, respectively, received either vehicle or a monoclonal antibody that sequesters sclerostin (anti-sclerostin) for 28 days. From days 21 to 28, animals also received sustained administration of the thymidine analog, bromodeoxyuridine (BrdU), which labels the DNA of dividing cells. Animals were then euthanized at day 28 and the femurs were examined for cortical bone formation, bone mineral density, and newly borne BrdU+ cells in the periosteum which is a tissue that is pivotally involved in the formation of new cortical bone. In both the geriatric and young mice, anti-sclerostin induced a significant increase in the thickness of the cortical bone, bone mineral density, and the proliferation of newly borne BrdU+ cells in the periosteum. These results suggest that even in geriatric animals, anti-sclerostin therapy can build new cortical bone and increase the proliferation of osteogenic cells and thus reduce the likelihood of painful age-related bone fractures.

A large number of bone fractures are treated with stabilisation devices that utilise metal wires or screws, which traverse the bone and are connected to an external frame or internal plate. Clinically, fixation devices are required to be able to: sustain loads; minimise patient discomfort and possible implant loosening; and promote healing. In the recent years locking plates have become increasingly popular for osteoporotic or complex fractures, which can be difficult to manage. It, however, remains unclear as to how these devices need to be configured for optimum clinical performance. This thesis investigates the mechanics of locking plates, factors that influence their performance and provides guidance to optimise the placement of screws. Finite element simulation and analytical models were developed and validated using lab-based experimental models. The local behaviour around the screw-bone interface is considered and the implications of different modelling assumptions assessed. A novel method of simulating the effect of radial interference due to pilot-hole size is proposed. Different screw types are evaluated: osteoporotic bone is found to be particularly susceptible to the screw tightening preload used in compression screws; far-cortical locking screws are found to slightly reduce device stiffness but substantially increase strain levels around screw holes. Finite element simulations show that many of the local effects, such as preloads and contact modelling, can profoundly influence the prediction of strains around screws but do not generally influence the global load-displacement behaviour; the screw-plate connection and bone/plate material and geometric properties are found to have an influence on global stiffness predictions. The key determinants of load-displacement behaviour evaluated through models are the loading and restraint conditions, which explain the huge range of stiffness predictions in the literature (three orders of magnitude). An analytical model based on 7 bone-plate construct parameters is developed. Despite its simplicity, the model is found to be able to predict the axial stiffness for experimental tests conducted and for 16 other cases from five previous studies with an average error of 20%. The manner of load application, not considered in the literature, is shown to dramatically alter predictions of plate stress, strains within the bone and conclusions regarding screw placement. Even with the inclusion of muscles forces, the choice of restraint condition dominates the mechanical behaviour. Using the models, the influence of screw position is systematically evaluated in varying bone qualities under axial loading and torsion and guidance for optimising fixation is developed.

In recent years, causewayed enclosures have come to be regarded as being ceremonial or ritual sites. This classification is derived from a perceived lack of evidence pertaining to domestic settlement, in the form of houses and 'typical' domestic animal bone assemblages, and a perceived abundance of 'atypical' material and methods of deposition. This thesis explores the animal bone from the Etton causewayed enclosure in order to ascertain whether these perceptions have an empirical basis. Etton was excavated in the 1980s, and the published literature relating to the site appeared to conform to the stereotypes established for causewayed enclosure sites, however during preliminary analysis, it became clear that the animal bone data was not complete and that many of the inferences regarding the role of animals at Etton were the result of presumption or data being taken out of context. Specifically, this thesis looks at the nature of the fractures on the animal bones from Etton, and also from a similar causewayed enclosure at Staines in order to establish a clear taphonomic history for the faunal remains on the site, from which aspects of the role of animals can be deduced. In archaeological literature the absence of 'fresh', or helical fractures (which tend to result from the conscious decision to break a bone for marrow) is said to support the hypothesis that sites of this type were not domestic in nature. This assertion has been made despite the fact that no detailed studies into bone fracture at Neolithic sites have ever been undertaken. This thesis demonstrates that at both Etton and Staines, fresh fractures were abundant and considers the potential implications of this for these sites. In so doing it highlights the dangers of presuming evidence exists or does not exist, and of cherry-picking data to fit a preordained ideal rather than allowing the data to speak for itself. At Etton and Staines, the animal bone speaks not necessarily of a categorically ceremonial or ritual economy, divorced from the domestic economy of the time, but of a more mundane economy, with occasional 'atypical' activity, that was standard for the inhabitants of causewayed enclosures, whether at this type of site or elsewhere.

Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / O propósito do presente trabalho foi investigar a participação da proliferação celular e da expressão dos componentes da matriz extracelular na cascata de eventos do processo de reparo da fratura óssea, empregando as técnicas histológica, imunohistoquímica e morfométrica, em um modelo experimental padronizado para a indução da lesão na tíbia de ratos a partir do método empregado por Yuehuei e Friedman7. É importante padronizar um modelo de indução da fratura, para posterior investigação da participação das células e dos componentes da matriz extracelular no processo de reparo da fratura, considerando que o tempo de consolidação depende significantemente da natureza e do tipo da lesão produzida. Quarenta (n = 40) ratos Wistar foram submetidos a fratura . Os animais foram avaliados em oito (n = 8) grupos de cinco (n = 5) animais, cada grupo emperimental com 12, 24, 48, 72, 96, 144, 192 e 240 horas após a fratura (12h até 10 dias). As fraturas foram classificadas de acordo com o sistema de classificação internacional de fratura de Muller100, AO (Associação para Osteosíntese). Foram encontradas fraturas simples em 86% do total, sendo 68% de fraturas transversas e 18% de fraturas obliquas, 14% do total de fraturas foram complexas, sendo 8% de fraturas irregulares e 6% de fraturas segmentares. Esses resultados demonstram que o aparelho permite padronizar radiológicamente o tipo de fratura, caracterizado pela linha que separa os fragmentos ósseos. Os resultados qualitativos dos componentes da matriz extracelular para TGF-β, VEGF, colágeno I e II, osteopontina, proteoglicanos, fibras do sistema elástico com a coloração de resorcina funcsina de Weigert, e para proliferação celular pelo PCNA, assim como os resultados morfométricos, sugerem que a modulação da expressão dos componentes da matriz extracelular e a proliferação celular durante o processo de reparo da fratura não é homogênea para todos os componentes teciduais, dependendo significantemente das tensões locais geradas pelo tipo da linha de fratura que pode ser determinante no tempo de regeneração do osso e na qualidade da restauração das propriedades biomecânica. Nossos achados podem contribuir para melhor compreensão da reparo de fratura óssea e para novas abordagens terapêuticas que considerem as propriedades biomecânicas do tecido ósseo em reparo nas suas diferentes etapas / The purpose of this study was to investigate the role of cells proliferation and extracellular matrix components expression in the process of bone fracture repair. To do so it used histological techniques, immunohistochemistry and morphometric analysis as well as a standardized experimental model for the induction of injury to the tibia of rats as proposed by Yuehuei and Friedman7. It is important to standardize a model of fracture induction for further investigation of the involvement of cells and extracellular matrix components in the fracture repair process, whereas the healing time depends significantly on the nature and type of lesion produced. Forty (n = 40) Wistar rats were subjected to fracture. The animals were divided into eight (n = 8) groups of five (n = 5). Each subgroup was observed after 12, 24, 48, 72, 96, 144, 192 and 240 hours of fracture (12 to 10 days). Immediately afterwards, the fractures were classified according to the system of international classification of fracture by Muller100, AO (Association for Osteosynthesis). Simple fractures were found in 86% of the total, among them, 68% were transverse and 18% were oblique. Complex fractures were found in 14% of the cases, among them 8% were irregular and 6% were segmental. These results demonstrated that the device enables researchers to standardize the type of fracture by X-ray, marked by the line separating the bone fragments. The qualitative results of the cells and extracellular matrix components of TGF-β, VEGF, PCNA, collagen I and II, osteopontin, proteoglycans, elastic fibers system with resorcin funcsin of Weigert, as well as the morphometric results suggest that the repair process of the fracture is not homogeneous for all components. Expression of the extracellular matrix components and cell proliferation modulation significantly depends on the local stresses generated by the type of the fracture. Such type can be decisive in determining time duration for bone regeneration and quality of the biomechanical properties restoration. Our findings may contribute to better understanding of bone fracture repair and for new therapeutic approaches that consider the biomechanical properties of bone tissue in repair in its different stages