Extended periods of mechanical unloading are known to be detrimental to bone health. Astronauts who spend months in microgravity aboard the International Space Station (ISS) are at particular risk. It is anticipated that NASA will not drastically increase the size of the astronaut corps, and this will mean increased likelihood of repeat missions for more astronauts. Thus, it is important to better understand the effects that prolonged, multiple bouts of unloading have on bone. This study utilized the hindlimb unloaded (HU) rat model to examine bone loss and recovery for single and double unloading bouts. Adult male Sprague-Dawley rats (6 months old) were randomized into the following groups: baseline (sacrificed at 6 months), 1HU7 (unloaded for 1 month, weight-bearing recovery for 3 months), 2HU10 (unloaded for 1 month, recovered for 2 months, unloaded for another month, and then recovered 2 months), 1HU10 (normal cage activity until 1 month HU ending at month 10, 2 month recovery followed), and aging controls (remained ambulatory throughout experiment). Every month (28 days), animals were terminated and the left femurs were excised, resulting in n=15 per group for each time point. Mineral and geometric properties were measured using peripheral quantitative computed tomography (pQCT) at the distal femur metaphysis, and quasi-static reduced platen compression (RPC) was used to estimate the mechanical properties of cancellous bone. Strength indices based on pQCT parameters were calculated as predictors of mechanical properties. Bone mass properties decreased due to HU and recovered within 2-3 months post-HU. A combination of increased periosteal apposition and endocortical resorption also occurred during HU. The initial HU bout suppressed normal age-related increases in mechanical properties and recovered within 1-2 months. Cancellous compressive strength index (CSI) most closely matched changes in mechanical properties. A second HU bout after two months recovery had a less detrimental effect on pQCT parameters but a greater negative impact on mechanical properties, when compared to pre-HU values. The opposite is true for mechanical properties if loss is characterized relative to aging controls. Recovery after the second HU period did not appear to be significantly affected by a previous bout of HU.

La morphologie des os humains varie en fonction du sexe, de l'âge et de l'ethnie. Cette variabilité de l'anatomie humaine peut aider à déterminer le sexe, l'âge et l'ethnie. Les outils utilisés pour de telles analyses sont classiquement des méthodes ostéométriques (longueur, angle, rapport de longueur) qui peuvent être sujettes à des biais d'analyse ou d'interprétation. L'analyse morphométrique géométrique 3D (MG) permet de limiter ces biais. Elle étudie et compare la forme d'un ou plusieurs objets en éliminant les effets liés à la taille de celui-ci. Nous n'avons pas retrouvé d'analyse du dimorphisme sexuel, ethnique et lié à l'âge de l'extrémité distale du fémur à l'aide de cette méthode. Le fémur est pourtant un des plus gros os du corps et il est souvent bien conservé dans les restes humains. L'objectif de ce travail était de montrer qu'il existe une différence de forme du fémur distal en fonction de l'âge, du sexe et de l'ethnie visualisable grâce à MG. Nous avons réalisé une MG de 482 scanners d'extrémité distale de fémur de sujets vivant dans le sud de la France et dans la région de Chongqing (chine). Les sujets présentant une pathologie osseuse ou articulaires ont été exclus. Dix landmarks ont été positionnés sur des reconstructions tridimentionelles. Nous avons également réalisé une analyse ostéométrique " classique " en plus de MG afin d'évaluer la vraisemblance de nos résultats. Les données ont été analysées par deux observateurs à deux temps différents. Nous avons calculé pour chaque landmark la variabilité inter et intraobservateur. Les landmarks choisis permettaient de caractériser la forme de l'extrémité distale du fémur. La première étape a consisté en la réalisation d'une analyse généralisée procrustre (GPA). Les coordonnées dans l'espace des landmarks ont été analysées en utilisant une analyse en composant principal (PCA). Une analyse discriminante a permis de vérifier le pourcentage de cas dans lequel le sexe, l'âge ou l'ethnie estimés étaient les bons. GPA retrouve une différence de forme statistiquement significative entre les sexes, en fonction de l'âge et entre les ethnies. PCA retrouve une différence de forme en fonction de l'âge, du sexe ou de l'ethnie qui représente respectivement 54,4 ;58,6 et 61,9% de la variabilité observée. Les taux d'assignement correct avec cette méthode étaient de 80% (âge) ; 77,3% (sexe) et 82 % (l'ethnie). L'analyse ostéométrique " classique " retrouvait des valeurs comparables à celles retrouvées dans la littérature. Le pourcentage d'erreur intra et inter observateur pour l'ensemble des landmarks n'excédait jamais 2%. Nous avons démontré que l'analyse MG du fémur distal permettait de mettre en évidence une variabilité en fonction du sexe, de l'âge et de l'ethnie de ce segment osseux. La reproductibilité élevée et la vraisemblance des résultats valident notre méthodologie. Cette différence de forme a des retombées directes en anthropobiologie mais aussi en orthopédie. Cette méthode d'assignation ne donne pas de résultats suffisamment précis pour être utilisée seule. Cependant, elle a l'avantage de pouvoir être utilisée dans des contextes d'autopsie virtuelle ou in vivo. Par ailleurs, par la présente étude nous réactualisons les données morphométriques de population contemporaine du sud de la France et aussi de la région de Chongqing en chine. Cette méthodologie adéquate et reproductible va permettre de réaliser des comparaisons diachroniques ainsi qu'inter ethnique. La validation de l'utilisation d'examen d'imagerie médicaux ouvre un champ nouveau en anthropologie physique. En ce qui concerne l'aspect orthopédique, cette variabilité questionne sur la nécessité ou non d'implant spécifique et surtout sur la nécessité de réévaluer de manière régulière la forme des prothèses de genou. / The shape of human bones varies based on age, sex and ethnicity. This variability in human anatomy can be used to determine a person's age, sex and ethnicity. Historically, the tools used for such analyses are osteometric methods (length, angle, length ratio) that can be plagued by analysis or interpretation biases. Three-dimensional geometric morphometric analysis (3D GM) can limit the impact of these biases. It is used to describe and compare the general shape of one or more objects by eliminating any size-related effects. To the best of our knowledge, this method has never been used to analyse the sexual dimorphism, ethnicity-related and age-related differences in the distal femur. The femur is one of the longest human bones and is often well preserved in human remains. The goal of this study was to demonstrate differences in the shape of the distal femur according to age, sex and ethnicity using GM. We carried out 3D GM on 482 CT scans of the distal femur of adults living in the South of France and in the Chongqing region of China. Subjects with bone or joint pathologies were excluded. Ten landmarks were defined on 3D reconstructions of the distal femur. A standard osteometric analysis was performed in addition to the GM analysis to evaluate the plausibility of our results. The data were analysed by two observers at two different times. This allowed us to calculate the inter- and intra-observer variability for each landmark. The chosen landmarks were used to characterise the shape of the distal femur. The first step consisted of a generalized Procrustes analysis (GPA). The landmarks' coordinates in space were analysed using a principal component analysis (PCA). A discriminant analysis was performed to determine the percentage of cases in which the sex, age or ethnicity was correctly estimated. The GPA found a statistically significant difference in the distal femur shape between different sexes, ethnicity groups and age groups. The PCA found that age, sex and ethnicity accounted for 54.4%, 58.6% and 61.9% of the observed variability in distal femur shape, respectively. Using this method, 80% of cases were assigned the correct age, 77.3% the correct sex and 82% the correct ethnic group. The results of the osteometric analysis were comparable to published values. The percentage error for the intra- and interobserver comparisons for all the landmarks was always less than 2%. In this study, MG analysis of the distal femur revealed age-related, sex-related and ethnicity-related variability in the distal femur. The high reproducibility and plausibility of our results validate our methodology. These shape differences have direct implications for anthropobiology and also orthopaedics. Although this method is not sufficiently accurate to be used alone, it has the advantage of being usable in the context of virtual or in vivo autopsy cases. Moreover, this study has updated the morphometric data for a modern population in the south of France and the Chongqing region of China. This reliable and accurate methodology can be used to perform diachronic and interethnic comparisons. Validation of this medical imaging modality opens new avenues in physical anthropology research. In the orthopaedics field, this variability means that the shape of implants used for knee arthroplasty should be re-assessed regularly and brings into question the need for gender-specific or ethnicity-specific implants.

Magnetic resonance imaging (MRI) has become the most important modality for assessment of pathological changes in the knee cartilage. The assessment of the cartilage is usually made by a set of anatomical MRI images with different sequences. Newer techniques, that map various in MRI parameters, have been developed and allows changes in an earlier stage of the disease. One of these techniques is T2 mapping. The goal of this thesis was to compare this newer technique, T2 mapping, with the standard MRI assessment for assessment of articular cartilage on distal femur in the knee. The purpose was to assess the cartilage with these two different methods and analyze its outcomes. Eight subjects were included in this study and scanned with a 3.0 T or 1.5 T MRI machine. A specific MRI knee protocol was used for the standard MRI assessment, and a multi-echo sequence was used for the T2 mapping. The T2 map was created and analyzed in the program IntelliSpace Portal. Both the standard MRI assessment and the T2 map showed changes in the knee cartilage. The result showed either indication for damage cartilage or healthy cartilage. The standard assessment showed cartilage lesion in three subjects and no lesion in five subjects. The same outcomes were with the T2 mapping. However, not all results were equal. The T2 mapping also showed higher values in the trochlea area where no indications for changes were found in the standard assessment. This study showed similar results for both the standard assessment and the T2 map. Both methods could identify damage and is, therefore, useful for assessment of the knee cartilage. The outcomes of the different methods differ, and the assessment is therefore made in different ways. The T2 mapping can be analyzed both visual and quantitative. The outcomes were both a color map of the knee but also results in graphs and values. The standard assessment is only assessed from grayscale images. The best outcomes from the T2 mapping was when it only was changes within the cartilage and not when the cartilage lesion was adjacent to an underlying bone lesion. Based on what was examined in this work, the best result was when T2 mapping was used together with the anatomical images used in the standard assessment. The conclusion is that the standard assessment is necessary when it comes to make a damage assessment and perform damage marking as for Episurf. The T2 mapping is, however, an interesting method and will be more useful with more applications in the future. It is therefore exciting to keep an eye on the technology and its development. / Magnetisk resonanstomografi (MR) har blivit den viktigaste modaliteten vid bedömning av patologiska förändingar i knäbrosket. Bedömningen av brosket görs vanligtvis med hjälp av anatomiska MR bilder som är skannade med olika sekvenser för att få olika viktningar på bilderna. En nyare teknik, T2 mappning, som kartlägger olika MR prameterar, har utvecklats för att med hjälp av andra parametrar analysera knäbrosket. Den här tekniken har resulterat i att förändringar i brosket kan upptäckas vid ett tidigare stadie i sjukdomsförloppet. Målet med det här examensarbetet var att jämföra de olika teknikerna, T2 mappning och MR-standardbedömningen, för att bedöma ledbrosket på distala lårbenet i knäet. Syftet var att bedöma brosket utifrån dessa olika metoder samt att analysera och jämföra dess resultat. Åtta subjekt ingick i studien och skannades med en 3,0 T eller 1,5 T MR-maskin. Ett specifikt MR-knäprotokoll användes för att skanna sekvenserna som ingick i standard bedömningen och en multi-ekosekvens användes för T2 mappningen. T2-mappningen skapades och analyserades sedan i programmet IntelliSpace Portal. Både standard MR-bedömningen och T2-mappningen visade tydliga förändringar i brosket. Resultatet visade antingen indikationer på skadat eller friskt brosk. Standardbedömningen visade broskskador hos tre subjekt och inga broskskador hos fem subjekt. Samma resultat visades med T2-mappningen. Däremot skilde sig vissa resultat mellan T2 mappningen och standardbedömningen. Då denna studie visade liknande resultat för både standardbedömningen och T2-mappningen, är båda metoderna användbara för bedömning av knäbrosket. De olika metoderna har olika utfall vilket gör att bedömningen sker på olika sätt. I T2 mapping får man ut både en färgkarta över knät men också grafter och värden som kan användas. I standardbedömningen görs bedömningen bara utifrån olika gråskalebilder. T2 mappningen var mest användbar när det var tydliga förändingar i bara brosket och inte när skadan mest var i benet. Det bästa resultatet var däremot när T2 mappning användes tillsammans med standardbedömningen. Slutsatsen är att standardbedömningen är nödvändig när det kommer till att bedömma skador och göra en skademarkering så som för Episurf. T2 mapping är däremot en väldigt intressant teknik men är idag inte en vanlig teknik inom diagnostiken och saknar just nu något tydligt användningsområde. Däremot, finns det stor potential och kommer troligtvis bli vanligare och få fler användingsområden i framtiden.

<p>Current stabilization methods for periprosthetic fractures of the distal femur have been inadequate in achieving sufficient fixation and can lead to complications rates as high as 29%. Therefore, the overall objective of this study was to design, manufacture and evaluate (experimentally and computationally) a novel plating method for improving the treatment of periprosthetic fractures of the distal femur.</p> <p>Medial and lateral prototype plates were designed and manufactured based on the geometry of a synthetic femur and a femoral prosthesis. The two plates were linked via a compression screw and a small tab on each plate that inserts into pre-existing slots on the prosthesis to enhance rigidity of the construct. Synthetic femurs were used to assess the ability of the prototype plates to stabilize a periprosthetic fracture compared to a traditional single lateral plate. Each femur was subjected to a testing protocol that involved compressive and bending loading of the sample. The relative motion between the distal and proximal fragments during loading was then measured using both 2D and 3D motion tracking techniques. Both techniques revealed that the prototype bilateral plates were able to reduce motion of the fracture site compared to a single lateral plate.</p> <p>The final objective concerned the development of a finite element model to represent the experimental testing. The fracture gap motion obtained from the final model did not completely agree with the experimental data; however, additional experimental measurements found that the majority of these differences could be attributed to simplification made at the tab-slot interaction. Despite the difference, the model represents a significant step forward in the simulation of periprosthetic fracture treatment, and further refinement would allow for optimization of the plate design.</p> <p>Overall, the results of this thesis indicate that an alternative approach to treating periprosthetic fractures exists that is capable of improving fracture stabilization.</p> / Master of Applied Science (MASc)

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.