Novel methodology for assessing cement injection behaviour in cancellous bone

Understanding the cement injection behaviour in cancellous bone and accurately predicting the cement placement within the vertebral body is extremely challenging. We propose a novel method using reproducible and pathologically representative 2D and 3D bone surrogates to help study the influence of cement properties on injection behaviour. Bespoke methodology was developed to control the injection volume and flow rate, measure the injection pressure, and allow visualization and quantitative analysis of the spreading distribution. Morphology analysis showed that the variability in the 2D and 3D bone surrogates was very low, indicating that the geometrical structure of the surrogates was constant. The overall pore size of the surrogates was very similar to that reported for human osteoporotic vertebral cancellous bone, indicating that the surrogates were pathologically representative. Injections performed into the 3D surrogates revealed that an increase in the fluid starting viscosity significantly increases the injection pressure in all surrogates, decreases the risk of leakage for osteoporosis surrogates only, decreases the mean spreading distance for multiple myeloma surrogates only and increases the sphericity causing a more uniform spreading pattern for the metastasis surrogates only. Injections performed into the 2D surrogates highlighted the influence of cement formulations and model structure on the injection behaviour and showed that (i) cements with similar composition/particle size have similar flow behaviour, (ii) cements with a high liquid-to-powder ratio cause irregular filling patterns and have a high risk of leakage, and (iii) the injection behaviour of certain cement formulations improves in the presence of lesion or fracture, suggesting the notion of pathology specific bone cements. The developed methodology provides a fast, robust tool for discerning subtle differences in bone cement formulations and allows comprehensive assessment of cement flow behaviour through controlling the surrogate morphology, controlling the injection parameters, measuring the injection pressure, and allowing the visualization and quantitative analysis of the spreading distribution. The advantage of this methodology is that it provides a clinically relevant representation of cement flow patterns and a tool for validating computational simulations

Physics of Complex Plasmas.

Physics of complex plasmas is a wide and varied field. In the context of this PhD thesis I present the major results from my research on fundamental properties of the plasma sheath, the plasma dust interaction, non-Hamiltonian dynamics, and on non-equilibrium phase transitions, using complex plasmas as a model system. The first chapter provides a short overview of the development of physics of Complex Plasmas. From fundamental plasma physics, properties of dust in plasmas, to the exceptional and unique features of complex plasmas. A summary of twenty years of research topics is also presented. This is followed by three chapters that illustrate publications based on experiments I did during my PhD. These publications, in my opinion, reflect nicely the large diversity of complex plasma research. • The investigation of nonlinear vertical oscillations of a particle in a sheath of an rf discharge was a simultaneous test of (pre-)sheath models and parameters. The nonlinear oscillations were shown to derive from a (strong) nonlinearity of the local sheath potential. They could be described quantitatively applying the theory of anharmonic oscillations, and the first two anharmonic terms in an expansion of the sheath potential were measured. On top of that we provided a simple experimentally, theoretically and mathematically based method that allows for in situ measurement of these coefficients for other experimental conditions. • The vertical pairing of identical particles suspended in the plasma sheath demonstrated some of the unique features that complex plasmas have as an open (non-Hamiltonian) system. Particle interaction becomes non-reciprocal in the presence of streaming ions. The symmetry breaking allows for mode-coupling of in plane and out of plane motion of particles. • Lane formation is a non-equilibrium phase transition. I summarize the main result of my papers on the dynamics of lane formation, i.e., the temporal evolution of lanes. This is followed by an outlook on my future research on non-equilibrium phase transitions, how they relate to our research of systems at the critical point, and how they allow us to test fundamental theories of charging of particles and the shielding of the resulting surface potential. Finally there is an appendix on the scaling index method. A versatile mathematical tool to quantify structural differences / peculiarities in data, that I used to define a suitable order parameter for lane formation

The Development Of Test Protocols For Padded Clothing In Rugby Union Using Human Tissue Impact Surrogates

Padded clothing (shoulder padding) is worn in Rugby Union to allow players to protect themselves. A performance specification for padded clothing has been set out by World Rugby™, with the intention that padding only protects against Cuts and Abrasions [1]. This performance specification is set out in Regulation 12 (padded clothing) [2]. This limits its density (45 + 15 kg·m-3), thickness (10 + 2 mm) and impact attenuation performance (acceleration > 150 g for a 14.7 J impact). Regulation 12 was critiqued and areas for improvement were identified. A literature review was conducted, covering injury and protection in Rugby Union, injury modes, anatomy of the human shoulder, organic tissue properties and human tissue simulants. It was identified that padded clothing’s ability to prevent Cut and Abrasion injuries have yet to be quantitatively assessed. This was crucial in improving the Regulation 12 test protocols. To address this problem, a multi-faceted investigation was performed. To start with, assessments were made of rugby players’ external and internal shoulder anatomies using 3D and ultrasound scanning techniques. From this, geometries of rugby players’ shoulders were found. The material properties of organic tissues were also assessed, with the focus being on the tissue’s compressive response to load. The reason for this work was to aid the fabrication of a human shoulder surrogate. Both a simplified and anatomical human shoulder surrogate were fabricated using human tissue simulants, as well as 3D printing and moulding techniques. A bespoke muscle simulant was developed with similar compressive properties to organic muscle tissue. Both the simplified and anatomical surrogates were integrated into various impact testing procedures. Padded clothing was tested for its force attenuative properties, its ability to prevent blunt force Cut and Abrasion injuries, and its ability to prevent stud-induced injuries. The results from this have led to informed recommendations 3 being made for the improved assessment of padded clothing in Rugby Union and therefore an improved Regulation 12. The research conducted in this thesis was the first to quantitatively assess padded rugby clothing’s ability to protect from specific injuries. As well as fabricate a human shoulder surrogate for the assessment of sports padding. The testing protocols developed in this thesis can be easily adapted for the assessment of protection or padding in other collision sports or even in other industries like ballistics or automotive

Markovianity of Trabecular networks

Clinically established methods to diagnose osteoporosis, a systemic disease with multiple implications to the human's well being are bound to the bone mineral density. Since it is well known, that the bone structure changes under osteoporosis, this thesis investigates, whether structural changes represent information independent of bone mineral density, and whether this structural information, obtained by innovative mathematical techniques improves first the ability to distinguish between osteoporotic and healthy structures, second the measurement of a risk to belong to the osteoporotic group, and third the prediction of a biomechanical measure, the failure load, compared to existing standard structural measures. By building a bridge between natural patterns of human cancellous bone to mathematical and stochastic algorithms capable of modeling complex structures this in vitro study proposed a successful way to catch the specifics of these natural patterns and to improve the current structural analysis methods. Methods investigated included Markov point processes, hidden Markov models and conditional entropie

Crystallization and demixing: morphological structure analysis in many-body systems

The description and analysis of spatial data is an omnipresent task in both science and industry: In the food industry the distribution and size of pores in baked goods plays a role in their taste. In chemistry, biology and physics spatial data arises in manifold disciplines and on all length scales. On large scales one finds them in the structure of the universe or in earth surveillance data. On small scales one observes highly structured data in inner bones or on minute scales in the deformation of nucleons in nuclear pasta, which is theorized to form during the cooling of a neutron star. In particular in statistical physics many-body-systems have a tendency to collectively form complex structures by self-organization. These complex structures often allow to draw conclusions about the underlying physics. In order to formulate a quantitative relation between the physics of many-body-systems and their morphology, i.e. the spatial structure they assume, a quantitative description of this structure is essential. In this dissertation the spatial structure of phase transitions (crystallization and demixing) in many-body-systems is quantitatively described and analyzed in order to achieve an improved understanding of the physics involved. Regarding the analysis methods applied in this thesis we go beyond conventional linear measures based on two-point correlation functions or the power spectrum. Instead, the aim is a full nonlinear morphological characterization of the spatial data with measures derived from the family of Minkowski functionals and tensors. They are additive, morphological measures related to, not only geometrical concepts like volume, area and curvature, but also to topological aspects such as connectivity and are sensitive to higher order correlation. Complex plasmas (dielectric microparticles immersed in a plasma) are a well suited model system for the particle resolved investigation of many-body processes. Their optical thinness allows for the optical imaging and tracking of the fully resolved trajectories of hundreds of particle layers. Additionally interactions can be tuned over a large range allowing to manipulate the shape and magnitude of the interparticle potential. Since the gas density is typically very low, the particle motion is practically undamped resulting in a direct analogy to the atomistic dynamics in solids or fluids. Liquid-solid phase transition have been considered impossible for a long time since the Mermin-Wagner theorem forbids long-range order in two (or less) dimensions. However, Kosterlitz and Thouless (Nobel prize 2016) circumvented this by replacing the long-range order with a quasi-long-range order and by introducing a topological phase transition mediated by defects. The well accepted KTHNY theory predicts an intermediate anisotropic phase, the hexatic phase. In the first part of this thesis the KTHNY theory is tested for experiments and a simulation of the crystallization of two-dimensional complex plasma sheets. For the same experiments the hypothesis and prediction of the recently developed fractal-domain-structure (FDS) theory is tested. The FDS theory is based on the Frenkel kinetic theory of melting. It postulates a fractal relationship between crystalline domains separated by boundaries of defect lines and predicts a scale-free relation between the system energy and the defect fraction. It is found that the KTHNY theory is not applicable to the liquid-solid phase transition in complex plasmas. The FDS theory however, is validated. The other focus of this thesis is the morphological characterization of fluid-fluid demixing dynamics. The generally accepted mechanism for fluid-fluid demixing is spinodal decomposition. Spinodal decomposition is achieved by a quench deep inside the spinodal curve of the phase diagram. It is characterized by the exponential growth of longwavelength density fluctuations. However the mean-field theory predictions of spinodal decomposition are not consistent with experiments and simulations. This shows the need for particle resolved studies with tunable interactions. To this end complex plasma simulations in flat three-dimensional space and density-functional theory calculations on the two-dimensional sphere are analyzed. In both cases different stages of demixing are identified with distinct domain growth rates during spinodal decomposition. Most importantly, universal demixing behavior is found for different interaction potentials, respectively for different mixture fractions and sphere sizes. These universal features could only be resolved by applying nonlinear measures, going beyond conventional methods based on the power spectral density. This suggests that nonlinear features in the demixing kinetics play an important role and that it is crucial to address this issue in future works.Räumliche Daten zu beschreiben und zu analysieren ist eine allgegenwärtige Problemstellung sowohl in der Wissenschaft als auch in der Industrie: So spielt beispielsweise in der Nahrungsmittelindustrie die räumliche Verteilung und die Größe von Poren in Backwaren eine Rolle für deren Geschmack. In den wissenschaftlichen Gebieten der Chemie, Biologie und der Physik liefern räumlich strukturierte Systeme Grundlage vieler Forschungsbereiche und sind in allen Größenordnungen aufzufinden: Auf großen Skalen z.B. bei der Struktur des Universums oder bei Erdbeobachtungsdaten. Auf kleinen Skalen bei der Struktur im inneren von Knochen oder im kleinsten bei der Verformung von Nukleonen zu nuklearer Pasta, die z.B. beim Abkühlen von Neutronensternen entstehen soll. Insbesondere in der statistischen Physik neigen Vielteilchensysteme dazu, sich in komplexen Strukturen selbst anzuordnen. Diese komplexen räumlichen Strukturen lassen oft Rückschlüsse auf die zugrunde liegende Physik zu. Um einen quantitativen Zusammenhang zwischen der Physik von Vielteilchensystemen und ihrer Morphologie, also der Struktur die diese annehmen, herzustellen, ist eine quantitative Beschreibung dieser Struktur unerlässlich. In dieser Dissertation werden daher die räumlichen Strukturen bei Phasenübergängen (Kristallisation und Entmischung) in Vielteilchensystemen beschrieben und analysiert, um damit Rückschlüsse auf die zugrundeliegende Physik ziehen zu können. Im Hinblick auf die Methoden, die zur Analyse der in dieser Dissertation untersuchten Systeme genutzt werden, gehen wir über konventionelle Methoden, die auf dem Leistungsspektrum oder auf zwei-Punkt Korrelationsfunktionen beruhen, hinaus. Das Ziel ist es die räumlichen Daten vollständig morphologisch zu charakterisieren. Zu diesem Zweck werden Metriken basierend auf der Familie der Minkowski Funktionale und Tensoren abgeleitet. Das sind additive morphologische Maße, die auch Korrelationen höherer Ordnung detektieren können. Sie sind nicht nur mit geometrischen Konzepten wie Volumen, Fläche und Krümmung verwandt, sondern stellen auch Aspekte der Topologie wie z.B. Verbundenheit dar. Komplexe Plasmen (dielektrische Mikropartikel eingebracht in ein Plasma) stellen ein überaus geeignetes Modellsystem für die Untersuchung von Vielteilchenprozessen auf der kinetischen Ebene individueller Teilchen dar, da durch ihre optische Dünnheit die Bildgebung mehrerer hundert Lagen von Teilchen und die volle Auflösung der Teilchentrajektorien ermöglicht wird. Darüber hinaus können die Teilchenwechselwirkungen in Komplexen Plasmen auf vielfältige Art und Weise manipuliert werden. Da der Gasdruck meist sehr gering ist, sind die Teilchenbewegungen praktisch ungedämpft. Dies stellt eine direkte Analogie zur Dynamik von Atomen in Flüssigkeiten oder Festkörpern dar. Flüssig-fest Phasenübergänge in zwei-dimensionalen Systemen wurden lange Zeit als unmöglich erachtet, da das Mermin-Wagner Theorem langreichweitige Ordnung in zwei (oder weniger) Dimensionen verbietet. Kosterlitz und Thouless umgingen diese Problem jedoch, indem sie die langreichweitige Ordnung durch eine quasi-langreichweitige Ordnung ersetzten und einen topologischen Phasenübergang vorstellten, der durch Interaktionen von Kristalldefekten vonstatten geht. Diese allgemein akzeptierte KTHNY Theorie sagt eine anisotrope Zwischenphase vorher, die so genannte hexatische Phase. Im ersten Teil dieser Dissertation werden die Vorhersagen der KTHNY Theorie, anhand von Experimenten und einer Computer Simulation an einzelnen zwei-dimensionalen Komplexen Plasma Kristall-Lagen getestet. Anhand selbiger Experimente wird eine kürzlich neu entwickelte fraktale-Domänen-Struktur (FDS) Theorie getestet. Die FDS Theorie basiert auf der kinetischen Theorie des Schmelzens von Frenkel. Sie postuliert einen fraktalen Zusammenhang zwischen der eingeschlossenen Fläche von kristallinen Domänen und der Länge deren Begrenzung durch Linien aus Kristalldefekten. Es wird gezeigt, dass die KTHNY Theorie nicht auf flüssig-fest Phasenübergänge in zwei-dimensionalen Komplexen Plasmen angewandt werden kann. Die FDS Theorie wird hingegen validiert. Desweiteren wird in dieser Dissertation die morphologische Beschreibung der Entmischungsdynamik von Flüssigkeiten behandelt. Der allgemein anerkannte Mechanismus, der für die Flüssigkeitsentmischung verantwortlich ist, ist die spinodale Dekomposition. Diese wird durch das quenchen (z.B. abkühlen) in den inneren Bereich der spinodalen Kurve im Phasendiagramm ausgelöst. Das charakteristische Merkmal der spinodalen Dekomposition ist der Beginn der Entmischung durch das exponentielle Wachstum von Dichtefluktuationen mit großen Wellenlängen. Die Vorhersagen der Molekularfeldtheorie der spinodalen Dekomposition sind jedoch nicht mit experimentellen Beobachtungen und Simulationen vereinbar. Diese Tatsache zeigt den Bedarf an Studien auf, die es vermögen einzelnen Teilchen zu folgen und bei denen man die Interaktionen zwischen den Teilchen beeinflussen kann. Deshalb werden in dieser Doktorarbeit sowohl Simulationen von Komplexen Plasmen (in drei-dimensionaler Euklidscher Geometrie) als auch Dichtefunktionaltheorie Berechnungen auf der zwei-dimensionalen Sphäre untersucht. In beiden Fällen können verschiedene Stadien in der Dynamik der Entmischung unterschieden werden. Das interessanteste Ergebnis ist die Entdeckung von universellem Verhalten im Entmischungsprozess. Universalität kann in dieser Arbeit im Hinblick auf verschiedene Interaktionspotentiale, bzw. im Hinblick auf verschiedene Mischungsverhältnisse und Sphärenradien gezeigt werden. Um diese universellen Eigenschaften zu entdecken, ist die Anwendung nicht-linearer Maße zwingend erforderlich, konventionelle auf dem Leistungsspektrum basierende Maße sind hierfür unzureichend. Dies zeigt, dass die nicht-linearen Eigenschaften des Entmischungsprozesses eine wichtige Rolle spielen und ist deshalb ein Fokus künftiger Arbeitenzu diesem Thema

Caraterrizzazione biomecannica in vitro di vertebre naturali e trattate

The research aim of the present thesis was to investigate the in vitro biomechanical properties of human thoraco-lumbar natural and treated vertebral body, undergo prophylactic augmentation. To overcome some limitation of the current in vitro test methods, an anatomical reference frame for human vertebrae was formally defined and validated and the effects of in vitro boundary conditions on the strain experienced by vertebral body investigated. Moreover an integrated approach, which incorporated different measurement methods (strain gauges and digital volume correlation) at different dimensional scales was adopted to investigate natural and augmented vertebrae during non-destructive and destructive testing. The effects of prophylactic augmentation were investigated for the first time through digital volume correlation, which allowed to measure the state of strain inside the vertebral body, in the injected cement, and in the bone-cement interdigitated region of vertebrae, including the elastic regime, but also the internal micro-failure mechanisms. Findings showed that augmentation is not associated to a modification of the strain magnitude but rather to a re-arrangement of the higher strain due to an alteration of the load sharing between the trabecular core and the cement region. The most critical region was the interdigitated area, where the initial microdamage gradually spread across the surrounded trabecular bone. Prophylactic augmentation increased in some vertebrae the failure force required to damage the vertebrae, conversely in other case the failure force was lower than in the controls (not-augmented). This variability of the weakening/strengthening effect of prophylactic augmentation seems to support that the effect of augmentation depends on the quality of augmentation itself (amount, localization and distribution of the injected material). It is therefore reasonable to assume that to improve the outcomes of prophylactic augmentation, more attention should be dedicated to the quality of augmentation itself.L'obiettivo principale della tesi è la caratterizzazione biomeccanica di vertebre umani toraco-lombari naturali e sottoposte alla vertebroplastica profilattica. Per superare alcune limitazioni dei test in vitro, è stato per la prima volta definito e validato un sistema di riferimento in vitro per l'allineamento delle vertebre, ed è stato effettuato uno studio sugli effetti sulla distribuzione delle sollecitazioni al variare delle condizioni al contorno più comunemente utilizzate in letteratura. Questo studio si basa su un'approccio integrato che incorpora differenti metodi di misura delle sollecitazioni (estensimetri e digital volume correlation), utilizzati durante i test in campo elastico e a rottura. L'efficacia della vertebroplastica profilattica è stata investigata per la prima volta grazie alla Digital Volume Correlation, che permette di misurare lo stato di deformazione all'interno del corpo vertebrale a livello dell'osso trabecolare, nel cemento iniettato e all'interfaccia osso-cemento, sia in campo elastico che a rottura. Rispetto alle vertebre naturali i risultati mostrano che il trattamento non altera l'entità delle deformazioni bensì le zone di massimo stress, ciò è dovuto ad un'alterazione nella condivizione del carico tra il tessuto trabecolare e il cemento. la zona più critica si ha all'interfaccia osso-cemento, dove ha origine la frattura. In certi casi il trattamento aumenta la resistenza delle vertebre in altri casi la forza di rottura è inferiore a quella del controllo. Questa variabilità nelle prestazioni meccaniche delle vertebre aumentate dipende dalla qualità del trattamento stesso (quantità cemento, posizionamento e distribuzione)

Contributors to Proximal Femur Fracture Force: Multiscale Considerations of Rate, Toughness, and Bone Composition

Fall-related hip fractures are a major concern facing the older adult population, especially as rates of these injuries increasing worldwide. Based on the strong positive relationship between femoral areal bone mineral density (BMD) and femoral bone strength, various methods and tools have been developed to predict hip fracture risk and ultimately prevent these injuries. However, these BMD-based methods are currently limited in their sensitivity, with commonly used methods like the T-Score failing to predict approximately 70% of hip fracture case. This begs the question: What is currently limiting our ability to accurately predict hip fracture risk? One potential explanation is that currently established methods to predict bone strength may be limited as they are based on non-physiological, low loading rate experiments measuring bone strength. Additionally, current predictive methods are solely focused on the inorganic phase of bone which may limit their accuracy. Despite understanding the role of collagen in bone structure and on the mechanical properties of bone at the microscale, such as its influence on fracture toughness, the organic phase of bone has not been directly considered in the context of femoral bone strength and fall-related hip fractures. Therefore, the overarching purpose of this thesis was to investigate the contributions of loading rate, fracture toughness, and bone composition (including both the inorganic and organic phases of bone) on the strength of the proximal femur in the context of fall-related hip fractures. The secondary purpose of this thesis was to investigate the effect of bone-affecting inflammatory disease states on these factors. These purposes were achieved through four studies which aimed to answer the following questions: 1) Does a biofidelic experimental paradigm, a vertical drop tower hip impact simulator (HIS), produce different bone strength measures than a traditional low displacement rate material testing system (MTS) approach? 2) Does a predictive bone strength model developed using a biofidelic test paradigm result in a model that is more accurate than previously developed models? 3) Does collagen network integrity and connectivity affect the fracture toughness of inferior femoral neck cortical bone under impact-like loading? 4) Are metrics of collagen quality significant predictors of proximal femur bone strength? Matched pairs of fresh frozen cadaveric femurs were used to compare measures of femoral bone strength extracted from both inertially driven HIS experiments and constant displacement rate MTS experiments, with the femurs of each pair being split between experiments (Study 1). Using a separate sample of matched pairs of femurs, measures of proximal femur bone strength (Study 2) were linked to measures of fracture toughness and collagen connectivity of cortical bone samples from the inferior femoral neck of the paired contralateral femur (Study 3). This allowed for direct consideration of site-specific measures of toughness and collagen in predictions of femoral bone strength (Study 4). Although loading rate was significantly higher for specimens tested using the HIS in Study 1, there was no significant difference in the femoral bone strength measured between experimental paradigms. Within each experimental paradigm, there was a significant positive relationship between loading rate and bone strength which was likely mediated by individual specimen stiffness. In Study 2, the combination of femoral neck areal BMD, sex, and their interaction was identified as the strongest overall model for predicting femoral bone strength (adj. R2 = 0.688, p <0.001). Model predictions of bone strength from four published materials testing system-based models revealed that each model produced significantly lower predictions of bone strength compared to the model developed in this study. When split by sex, each of the published models predicted significantly lower bone strength for males when compared to measured values. Study 3 revealed a significant relationship between collagen network connectivity (Max Slope) and both elastic and elastic-plastic fracture toughness (KMax and JMax), of inferior femoral neck cortical bone samples when evaluated at, or up to, the point of peak load (adj. R2 = 0.229, p = 0.002, and adj. R2 = 0.163, p = 0.021, respectively). Collagen network thermal stability (Td), however, was not associated with fracture toughness. Towards addressing the secondary purpose of this thesis, presence of bone affecting disease states was considered as a categorical variable, where it was found to be significantly associated to fracture toughness metrics alongside Max Slope and led to a marked improvement of model strength for JMax (adj. R2 = 0.324, p = 0.003). After aggregating results for matched pairs of femurs that were split between Studies 2 and 3, regression analyses in Study 4 revealed that while fracture toughness was not associated with bone strength, Td was significantly associated with bone strength (adjusted R2 = 0.395, p = 0.017). Td explained an additional 3.2% of the variance in the prediction of femoral bone strength when included alongside BMD and sex. The combination of these three variables resulted in the strongest overall model predicting bone strength (adj. R2 = 0.942, p < 0.001). Considering that the Td is known to be associated with the connectivity of the collagen network, crosslinking content, and organization of the collagen network, this finding suggests that these molecular level characteristics of bone collagen are important contributors to femoral bone strength. Through multiscale investigations of whole bone strength at the macroscale and characterization of aspects of the collagen network at the micro-scale, this thesis represents the first investigations to directly measure the influence of collagen on whole bone strength, specifically in the context of fall-related hip fractures. The aspects of collagen connectivity captured by Td were found to significantly contribute to femoral bone strength in simulated lateral hip impacts. However, the inclusion of Td as a predictor alongside BMD and sex only resulted in an additional 3.2% of the variance being explained, which brings into question the clinical significance of these findings. The difference between the bone strength regression model generated in Study 2 compared to other published models based on materials testing systems experiments suggests that it may be important to use more biofidelic test paradigms for the development of models to predict bone strength. These findings may lead to improvements in our ability to accurately predict femoral bone strength and consequently result in better estimations of injury risk. By improving the accuracy of our estimates of injury risk, we can ultimately aid in the prevention of fall-related hip fractures. Further research into the molecular-level aspects of collagen that relate to Td is needed to properly understand the mechanism through which collagen contributes to bone strength. This would then allow for the identification of potential biomarkers that could be used clinically to estimate bone strength

Multiscale Geometric Methods for Isolating Exercise Induced Morphological Adaptations in the Proximal Femur

The importance of skeletal bone in the functioning of the human body is well-established and acknowledged. Less pervasive among the populace, is the understanding of bone as an adaptive tissue which modulates itself to achieve the most construction sufficient for the role it is habituated to. These mechanisms are more pronounced in the long load bearing bones such as the femur. The proximal femur especially, functions under significant loads and does so with high degree of articulation, making it critical to mobility. Thus, exercising to buttress health and reinforce tissue quality is just as applicable to bone as it is to muscles. However, the efficiency of the adaptive (modelling/remodelling) processes is subdued after maturity, which makes the understanding of its potential even more important. Classically, studies have translated the evaluation of strength in terms of its material and morphology. While the morphology of the femur is constrained within a particular phenotype, minor variations can have a significant bearing on its capability to withstand loads. Morphology has been studied at different scales and dimensions wherein parameters quantified as lengths, areas, volumes and curvatures in two and three dimensions contribute towards characterising strength. The challenge has been to isolate the regions that show response to habitual loads. This thesis seeks to build on the principles of computational anatomy and develop procedures to study the distribution of mechanically relevant parameters. Methods are presented that increase the spatial resolution of traditional cross-sectional studies and develop a conformal mapping procedure for proximal femur shape matching. In addition, prevalent methods in cross-sectional analyses and finite element simulations are employed to analyse the morphology of the unique dataset. The results present the spatial heterogeneity and a multi-scale understanding of the adaptive response in the proximal femur morphology to habitual exercise loading