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In England alone, the NHS carries out 30,000 total hip replacements each year, costing approximately £ 140 million. In some of these replacements loosening and subsidence are commonly seen within the initial six months post-operatively raising the possibility of secondary surgery. Revision surgery is more complex, risky and costly due to the increased amount of bone loss and bone damage associated with the removal of the primary prosthesis. Therefore, it makes perfect sense to focus resources towards alleviating early first implant failures and also prolonging the overall life of the implants. There is good evidence nowadays that many of these implant failure phenomena are brought about by the mechanical bone/implant interaction and are critically influenced by the bone tissue properties themselves. The present study focuses into the behaviour of cortical bone tissue under mechanical stress and in particular on the accumulation of both the recoverable (elastic) and irrecoverable (residual or 'plastic') strains. Strains are major contributors to either the deVelopment of damage within the bone matrix or to the bone remodelling process. Femoral bone specimens from 5 females (53-79 yrs old) and one 55 yr old male were fatigue cycled until failure in either tension, compression, or shear. This study found that the accumulation of both the elastic and plastic strain rates were dependent on the stress in each of the three loading modes (tension, compression, and shear) for each individual separately and also - when the data was pooled - regardless of the donor. However, the way plastic strain developed as function of elastic strain was independent of the applied stress. The material properties of the bone were also examined to see whether they had an effect on these strain patterns. The results showed that the two main contributors were the density of the tissue and the organic content of the test specimens. This is important in understanding how bone tissue will behave in fatigue, in general, and how it will behave around prostheses. It may also contribute towards predicting the long-term surgery outcome for various individuals of different ages and various bone characteristics. Therefore, the data and its analysis reported in this dissertation will be of particular benefit and interest to bioengineers working with FEA methods in applications of reconstructive surgery and in basic bone biomechanics research.

Attempts to understand the effects of ageing on the condition of a synovial joint. Knee joints of individuals with no known history of joint disease were examined and the pattern of cartilage damage was mapped macroscopically in a manner that allowed quantitation of the affected areas. / Bibliography: leaves 267-277. / vi, 277 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Pathology, 1993

Les récepteurs activés par les proliférateurs de peroxysomes (PPARs) sont des facteurs de transcription impliqués dans la régulation du métabolisme lipidique et de la tolérance au glucose. Les PPARs contrôlent également l’inflammation associée à de multiples pathologies, dont la polyarthrite rhumatoide. Dans les travaux présentés dans ce manuscrit, nous avons comparé les potentialités anti-arthritiques, dans un modèle expérimental, de deux agonistes synthétiques de haute affinité pour deux isotypes de PPARs, PPARα et PPARγ. Nous avons démontré qu’un traitement avec un agoniste sélectif de PPARγ, la pioglitazone, en plus de diminuer la sévérité de l’arthrite expérimentale, réduisait la perte osseuse inflammatoire en préservant la micro-architecture osseuse. Nous avons mis en évidence que PPARγ, d’une part, régulait l’expression locale et systémique de l’interleukine-17 et de RANKL, et que, d’autre part, il inhibait l’expression du facteur de transcription RORγt, acteur majeur de la voie IL-17/Th17. Les animaux déficients pour PPARγ nous ont permis de confirmer son rôle majeur dans le développement du processus arthritique. En effet, ces animaux présentent tous et de façon spontanée une arthrite associée à une augmentation du nombre de mastocytes capables de produire l’IL-17 et leur propre facteur de différenciation, le SCF dans la synoviale inflammatoire. Enfin, nous avons discuté le lien possible entre l'arthrite inflammatoire et la mastocytose à la lumière de l’étude d’un cas clinique d’un patient atteint de polyarthrite rhumatoïde concomitante à une mastocytose systémique / Peroxisome proliferator-activated receptors (PPARs) are transcription factors implicated in lipid metabolism and glucose tolerance. Once activated by specific agonists, PPARs control inflammation associated with numerous diseases, notably Rheumatoid arthritis. The first study presented here aim to compare the anti-arthritic potency of two high-affinity synthetic agonists for PPARα and PPARγ in an experimental model. Then we focused on the effect of pioglitazone, a high-affinity synthetic agonists for PPARγ, and demonstrated that a per os treatment with this agonist not only reduced experimental arthritis but also inhibited partly inflammation-related bone loss by preserving bone microarchitecture. We pointed out that PPARγ, on one hand, regulated local and systemic expression of interleukine-17 (IL-17) and RANKL and on the other hand, inhibited expression of transcription factor RORγt, a main regulator of IL-17/Th17 pathway. Study of mice deficient for PPARγ confirmed its major role in the development of the arthritic process since these mice developed spontaneously arthritis. Of interest arthritis in these mice is associated with increased number of synovial mast cells able to produce IL-17 and their own differenciation factor, the SCF. Finally, we discussed the possible link between inflammatory arthritis and mastocytosis in a case report of a patient suffering from rheumatoid arthritis concomitant to systemic mastocytosis

L’objectif de ce travail était de développer des stratégies éducatives en association avec une cure thermale à destination de patients porteurs de gonarthrose, avec un objectif non seulement d’efficacité clinique et psychologique mais aussi d’amélioration du niveau d’activité physique. Au total, 745 patients souffrants de gonarthrose ont été recrutés sur les 9 stations thermales membre du Cluster Innovatherm et répartis dans les 3 études composant ce projet. La première étude porte sur l’analyse qualitative des freins et des leviers à la pratique d’activité physique. La seconde étude a mesuré le niveau d’activité physique et analysé les facteurs influençant la régularité de la pratique. La troisième étude a évalué les effets d’un programme d’éducation à l’exercice en milieu thermal. L’analyse des résultats des 2 premières études a montré que le niveau d’activité physique des gonarthrosiques était significativement dépendant de certaines données sociodémographiques, anthropométriques (genre, indice de masse corporelle, obésité), de facteurs extrinsèques (lieu de vie, situation familiale) et de facteurs intrinsèques (motivation, bien être, « self-efficacy », fatigue, vieillissement, peur d’aggraver la gonarthrose). La troisième étude a montré que le traitement thermal associé ou non aux ateliers d’éducation à l’exercice permettait d’augmenter significativement le niveau d’activité physique, avec un effet taille moyen de 0.53 [0.28;0.77] à 3 mois. Les ateliers d’éducation à l’exercice ont un effet bénéfique significatif sur l’anxiété, la dépression et les peurs et croyances (sous item médecin du KOFBeQ), à 3 mois. Ces études confirment l’impact du traitement thermal sur les paramètres cliniques de la gonarthrose et fournissent de nouvelles données concernant ce traitement sur l’évolution du niveau d’activité physique. Cette étude argumente en faveur de l’effet cognitif et psychologique du programme d’éducation à l’exercice. / The aim of this work was to develop educational strategies in association with spa therapy treatment for patients with knee osteoarthritis, with a goal not only of clinical, psychological but also of improvement of the level of physical activity. A total of 745 patients with knee osteoarthritis were recruited from the 9 member’s thermal spa of the Innovatherm Cluster and distributed among the 3 studies building this project. The first study looked at the qualitative analysis of facilitators and barriers to physical activity. The second study on the level of physical activity and the analysis of the factors influencing the practice. The third study evaluated the effects of a self-management exercise education program in spa therapy resort. Analysis of the results of studies 1 and 2 showed the level of physical activity was significantly dependent on certain anthropometric data (gender, BMI, obesity), extrinsic factors (life situation, family situation) and intrinsic factors (motivation, well-being, self-efficacy, fatigue, aging, fear of aggravating knee osteoarthritis). Study 3 showed that spa treatment associated with or without self-management exercise program significantly increases the physical activity level, with medium effect size 0.53 [0.28; 0.77] at 3 months. Exercise education has a significant beneficial effect between groups in favor of the intervention group on anxiety, depression and fears and beliefs. These studies confirm the impact of spa therapy treatment on the clinical parameters of osteoarthritis and provide new data on the increase of the physical activity level and argue in favor of the cognitive and psychological effect of the self-management exercise program.