Magister Scientiae (Physiotherapy) - MSc(Physio) / Osteoarthritis (OA) is the major cause of pain and disability in the elderly, as well as people younger than the age of 45. Research reported the importance of conservative management of OA in the early stages, as it has proved to be effective in slowing down the progression of the disease, as well as reducing the secondary effects of decreased functional ability and disability. Early referral could assist with effective pain management, decrease in disease progression and increase in functional ability and quality of life. Therefore, the overall aim of the study was to establish a profile of patients with OA, as well as to explore the perceptions and experiences of health professionals regarding the conservative management of OA at a tertiary hospital in Nigeria. The study employed a sequential exploratory mixed method approach, using a retrospective and exploratory study design for the quantitative and qualitative phases respectively. Data was collected from one hundred and thirty-five medical records of patients with OA, meeting the inclusion criteria of the study, and admitted at the University of Calabar Teaching Hospital (UCTH) from 1 January 2012 to 31 December 2016. The patient sample was predominantly female (n=80; 93%), with a mean age of 51.85 years old (SD=13.73). Thirteen (13) health professionals, eight (8) physiotherapists and five (5) orthopedic surgeons participated in the interviews. The Statistical Package for Social Sciences (SPSS) version 24 was used to analyse quantitative data. Inferential and descriptive statistics were used to describe the results in terms of frequencies, percentages, means and standard deviation. Alpha level was set at 5%. Audio-taped qualitative data was transcribed verbatim, and analysed using categories and themes. Permission to conduct the study was obtained from the University of the Western Cape Biomedical Research Ethics Committee (BMREC).

The purpose of this dissertation research was to use markers of activity change to explore the effects of imperial expansion and sociopolitical upset on a population. This study focused on markers such as entheseal remodeling and the development and progression of osteoarthritis that are commonly used in bioarchaeological literature to assess changes in activity over time. Three populations were used, comprised of seven different sites, which are divided into the Late Medieval (pre-Ottoman), Early Modern (post-Ottoman), and Vlach populations. These sites come from both the Adriatic and continental region of Croatia and are curated at the Croatian Academy of Sciences and Arts – Anthropology Center. The skeleton is highly plastic, which allows it to serve as an archive for the lived experiences of the individual. Because of this plasticity, embodiment theory was employed as a lens through which to examine the changing activity of people under Ottoman rule. Historical narratives paint this time period as being rife with conflict, with a large proportion of the Croatian population being displaced, subsumed by the Ottoman threat, or killed. This is reported to have caused drastic changes in the daily lives of all Croatians across the country as they were forced to adapt to new rulers or leave their homes. This was tested by examining entheseal remodeling and osteoarthritis within the different populations. The data indicate that although there were some differences found between the time periods, the changes were not as drastic as what may have been expected from the historical data. This is perhaps due to most Croatian people at the time being serfs, living a rugged lifestyle on the lands of feudal lords. Although the Ottomans may have been relentless rulers, they may not have worked common Croatians more so than their Croatian lords. Most people probably remained in their roles as craftsmen or food producers, which would not have left dramatic changes in the form of activity markers on the skeleton.

L'obésité (Ob) est un facteur de risque majeur pour l'arthrose (OA). L'angiogenèse de l'os sous-chondral est impliquée dans la pathophysiologie de l'OA et peut réagir différemment aux facteurs de promotion de l'OA. L’objectif était de discriminer le rôle respectif de la charge liée au surpoids et des troubles métaboliques sur la dégradation articulaire et l'angiogenèse, dans un modèle de souris arthrosique. Des souris C57BL/6j ont subi une déstabilisation chirurgicale du ménisque médiale pour induire l'OA. Des souris OA-Mince ont ensuite été soumises à une hypergravité pour imiter les effets du surpoids. Les autres souris ont été conservées à 1g. Des souris OA-mince et des souris OA-Ob ont été traitées avec un anti-VEGF. Après la perfusion de baryum, le genou droit a été imagé et la microstructure osseuse, la moelle osseuse et les réseaux vasculaires sous-chondraux ont été quantifiés. L'histologie quantitative de l'os sous-chondral a été effectué. La dégradation du cartilage articulaire était similaire entre les groupes OA. L'hypergravité n'a pas aggravé l'amincissement du cartilage induit par l’OA mais a empêché l'épaississement lié à l'OA de la plaque osseuse sous-chondrale. Les souris OA-Ob avaient un volume osseux trabéculaire épiphysaire inférieur à celui des souris Mince-OA. L’OA a induit une angiogenèse à travers la plaque sous-chondrale dans les groupes OA-Mince 1g et 2g. En revanche, la densité vasculaire de la Mo était plus faible chez les OA-Ob que chez OA-Mince. L'obésité et le 2g ont eu des effets opposés sur la taille des vaisseaux. Le bevacizumab a empêché l'angiogenèse induite par l'OA dans le groupe OA-Mince mais n'a eu aucun effet dans le groupe Ob. / Obesity is a major risk factor for osteoarthritis (OA). Subchondral bone angiogenesis is involved in OA pathophysiology and may respond differently to OA promoting factors. Aim was to discriminate the respective role of overweight-related-load and of metabolic disorders due to fat accumulation, in joint degradation and angiogenesis, in a mouse model of surgically Induced knee osteoarthritis. C57BL/6j male mice underwent surgical medial meniscus destabilization (MMD) to induce OA and Lean mice were sham operated (Sham-lean). At 2 Mo, gps were fed with high fat diet to induce insulino-resistance and obesity (Ob). OA-Lean mice were then submitted to 2g hypergravity in a centrifuge to mimic the effects of overweight. OA-lean mice and OA-Ob mice were treated with an anti-VEGF. After barium infusion, the right knee was imaged by high-resolution and bone microstructure, bone marrow (bm) and subchrondral vascular networks were quantified. After MMA embedding, OARSI scoring and subchondral bone quantitative histology were then carried out at the medial tibia plateau.Articular cartilage degradation was similar between the OA groups.

by Linda, Fu Lap Kun. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1993. / Includes bibliographical references (leaves 115-128). / ACKNOWLEDGMENT --- p.i / TABLE OF CONTENTS --- p.ii / ABSTRACT --- p.xii / Chapter CHAPTER ONE: --- INTRODUCTION --- p.1 / Chapter CHAPTER TWO : --- LITERATURE REVIEW --- p.6 / Chapter 2.1 --- BIOLOGY OF ARTICULAR CARTILAGE --- p.7 / Chapter 2.1.1 --- Normal cartilage --- p.7 / Chapter 2.1.1.1 --- Composition and properties --- p.7 / Chapter 2.1.1.2 --- Morphology of normal cartilage --- p.12 / Chapter 2.1.2 --- Degeneration of cartilage --- p.12 / Chapter 2.1.2.1 --- Morphology of degenerative cartilage --- p.12 / Chapter 2.1.2.2 --- Biochemical characteristics of degenerative cartilage --- p.13 / Chapter 2.1.3 --- Healing of degenerated articular cartilage --- p.14 / Chapter 2.2 --- METHODS TO CREATE OSTEOARTHRITIS MODEL --- p.15 / Chapter 2.2.1 --- Immobilization --- p.16 / Chapter 2.2.2 --- Instability method --- p.16 / Chapter 2.3 --- SCORING OF OSTEOARTHRITIS --- p.17 / Chapter 2.3.1 --- Gross morphology --- p.17 / Chapter 2.3.1.1 --- Mapping of OA area --- p.17 / Chapter 2.3.1.2 --- Amount of synovial fluid --- p.18 / Chapter 2.3.1.3 --- Mobility --- p.18 / Chapter 2.3.2 --- Histological scoring --- p.18 / Chapter 2.3.3 --- Biochemical comparison --- p.21 / Chapter 2.3.3.1 --- Water content --- p.21 / Chapter 2.3.3.2 --- Proteoglycan --- p.21 / Chapter 2.4 --- THE TREATMENT OF OSTEOARTHRITIS --- p.23 / Chapter 2.4.1 --- Biology of Hyaluronic acid --- p.24 / Chapter 2.4.2 --- Repairing properties of Hyaluronic acid in OA --- p.24 / Chapter 2.4.3 --- The pharmacology of Hyalgan --- p.26 / Chapter 2.4.4 --- Intraarticular injection of Hyaluronic acid in animals --- p.26 / Chapter CHAPTER THREE: --- CREATING OSTEOARTHRITIC MODEL --- p.28 / Chapter 3.1 --- INTRODUCTION --- p.29 / Chapter 3.2 --- MATERIAL AND METHODOLOGY --- p.30 / Chapter 3.2.1 --- Animals --- p.30 / Chapter 3.2.2 --- Instabilization --- p.32 / Chapter 3.2.2.1 --- Reagent and Apparatus --- p.32 / Chapter 3.2.2.2 --- Procedure --- p.32 / Chapter 3.2.3 --- Immobilization --- p.36 / Chapter 3.2.3.1 --- Reagent and Apparatus --- p.36 / Chapter 3.2.3.2 --- Procedure --- p.37 / Chapter 3.3 --- METHODS OF ASSESSMENT --- p.39 / Chapter 3.3.1 --- Gross structure comparison --- p.40 / Chapter 3.3.1.1 --- Gross mapping of the OA areas --- p.40 / Chapter 3.3.2 --- Histochemical scoring --- p.40 / Chapter 3.3.2.1 --- Procedure --- p.40 / Chapter 3.3.2.1.1 --- Hematoxylin & eosin stain --- p.45 / Chapter 3.3.2.1.2 --- Safranin O stain --- p.45 / Chapter 3.3.3 --- Biochemical assessment --- p.47 / Chapter 3.3.3.1 --- Water content --- p.47 / Chapter 3.3.3.2 --- Proteoglycan content --- p.49 / Chapter 3.3.3.2.1 --- Reagent --- p.49 / Chapter 3.3.3.2.2 --- Procedure --- p.49 / Chapter 3.3.3.2.3 --- Standard curve --- p.52 / Chapter 3.4 --- METHODS OF STATISTICAL ANALYSIS --- p.53 / Chapter 3.5 --- RESULTS --- p.54 / Chapter 3.5.1 --- Gross morphology --- p.54 / Chapter 3.5.1.1 --- General appearance --- p.54 / Chapter 3.5.1.2 --- Gross osteoarthritic area --- p.56 / Chapter 3.5.2 --- Histological results --- p.59 / Chapter 3.5.2.1 --- Histological appearance --- p.59 / Chapter 3.5.3 --- Results of biochemical assay --- p.66 / Chapter 3.3.3.1 --- Water content --- p.66 / Chapter 3.5.3.2 --- Proteoglycan --- p.69 / Chapter 3.6 --- DISCUSSION --- p.72 / Chapter 3.6.1 --- Relation between gross OA area & Mankin's score --- p.72 / Chapter 3.6.2 --- Relation between gross OA area & GAG content --- p.74 / Chapter 3.6.3 --- Relation between Mankin's score & water content --- p.76 / Chapter 3.6.4 --- Relation between Mankin's score & GAG content --- p.78 / Chapter 3.6.5 --- Comparison of the four different parameters --- p.79 / Chapter 3.6.6 --- Merit on the four parameters --- p.84 / Chapter 3.6.6 --- Consistency & reproducible of the OA model --- p.85 / Chapter 3.6.7 --- Moderately severe OA model was needed in Part II --- p.86 / Chapter 3.7 --- CONCLUSION --- p.86 / Chapter CHAPTER FOUR: --- HEALING OF CARTILAGE --- p.87 / Chapter 4.1 --- INTRODUCTION --- p.88 / Chapter 4.2 --- MATERIALS AND METHODS --- p.89 / Chapter 4.2.1 --- Establishing the osteoarthritis --- p.89 / Chapter 4.2.2 --- Treatment of the rabbits --- p.90 / Chapter 4.2.2.1 --- Reagent and Apparatus --- p.90 / Chapter 4.2.2.2 --- Procedure --- p.91 / Chapter 4.2.3 --- Methods of assessment --- p.92 / Chapter 4.2.4 --- Methods of statistical analysis --- p.92 / Chapter 4.3 --- RESULTS --- p.93 / Chapter 4.3.1 --- Gross OA area --- p.94 / Chapter 4.3.2 --- Mankin's score --- p.97 / Chapter 4.3.3 --- Water content --- p.99 / Chapter 4.3.4 --- Proteoglycan . . --- p.101 / Chapter 4.3.5 --- Results of Part I and Part II --- p.103 / Chapter 4.4 --- DISCUSSION --- p.107 / Chapter 4.4.1 --- Morphological comparison --- p.107 / Chapter 4.4.2 --- Biochemical comparison --- p.110 / Chapter 4.4.3 --- Comparison of the results in two parts of experiment --- p.111 / Chapter 4.5 --- CONCLUSION --- p.113 / BIBLIOGRAPHY --- p.114 / APPENDIX --- p.129

OBJECTIVE: Osteoarthritis (OA) is a leading cause of disability worldwide. This disease is characterized by the inflammation and degradation of the cartilage and surrounding tissue in a joint. The disease manifests as either a result of years of wear and tear or after a joint injury. Post-traumatic osteoarthritis, as this latter case is named, is frequently studied since the exact trigger of the disease is known. In addition to several changes within the joint space, a significant alteration is the degradation of cartilage caused primarily by the release of inflammatory cytokines including interleukin-1 and 6 and tumor necrosis factor α. One current pharmacological treatment for the pain caused by OA is an intra-articular injection of glucocorticoids such as dexamethasone. As this is a common treatment, the goal of this research was to determine if, at the cellular level, this treatment impacts cell viability in the presence of pro-inflammatory cytokines. Another goal was to investigate how such treatment affects the progression of cartilage degradation caused by cytokines. OA results in the loss of the key extracellular matrix molecule, aggrecan, which contains negatively charged glycosaminoglycan (GAG) chains. Measurement of the amount of GAGs lost is an early indicator of cartilage degradation. In addition, biosynthesis of GAG chains can be measured to estimate the overall metabolic health of the cells. We hypothesized that dexamethasone blunts the harmful effects of proinflammatory cytokines and improves GAG biosynthesis and chondrocyte viability. METHODS: Cylindrical cartilage explants were collected from bovine knee joints and trimmed to a uniform 3 millimeters in diameter and 1 millimeter thick. Each treatment group consisted of n=6 explants from the same knee joint. In one set of experiments, these explants were subjected to two different doses of interleukin-1α (1 ng/mL and 10 ng/mL) with and without dexamethasone at 100 nM. In another set of experiments, explants were subjected to both interleukin-1α and tumor necrosis factor-α (1 ng/mL and 25 ng/mL respectively). The explants were cultured in medium for 6 days and were digested for outcome measurements on the final day. On day 4, 35S-sulfate was added to the explant medium for later measurement of radiolabel incorporation as a measure of GAG biosynthesis. Cell viability was measured on day 5 using red/green fluorescent viability dyes fluorescein diacetate (FDA) which stains live cells green and propidium iodide (PI) which stains dead cells red. RESULTS: Compared with untreated controls, explants subjected to the pro-inflammatory cytokines interleukin-1α and tumor necrosis factor-α exhibited greater glycosaminoglycan loss and a decrease in GAG biosynthesis. These treatments also decreased cell viability. Addition of dexamethasone improved cell viability compared to treatment with the cytokines. In addition, dexamethasone prevented glycosaminoglycan loss and increased GAG biosynthesis in the presence of interleukin-1α. However, dexamethasone did not prevent tumor necrosis factor-α mediated loss of GAGs. CONCLUSION: These studies demonstrated that dexamethasone inhibited specific aspects of cartilage degradation associated with inflammation in early OA. This therapeutic counteracts the degradative changes initiated by inflammatory cytokines such as interleukin-1α without compromising cell viability. Future studies are needed to identify the mechanisms of dexamethasone action and the ideal concentration to use if it is to be used as a treatment for OA following acute joint injury.

The synovium is a specialized connective tissue that encapsulates diarthrodial joints like the knee, maintaining a low-friction environment for the articulating surfaces within. This tissue plays a key role in homeostasis by regulating solute transport in and out of the joint, and secreting lubricating factors into the synovial fluid. The predominant cell type in the synovium is the fibroblast-like synoviocyte (FLS), which resides on the intimal surface of the tissue and produces lubricating molecules such as hyaluronan. Because these cells directly face the synovial fluid and apposing tissue surfaces within the joint, they are exposed to a dynamic environment of mechanical stimuli generated during daily activity. This dissertation addresses the global hypothesis that FLS are mechanosensitive to distinct modes of shear stress generated in the knee during articulation, and that modulation of this sensitivity by chemical and physical factors of the osteoarthritic (OA) environment contributes to disease progression. Previous work has demonstrated that fluid-induced shear stress, generated as synovial fluid redistributes within the capsule during articulation, is a relevant mechanical stimulus for FLS. Exposure of FLS to fluid shear has been shown to modulate downstream functions such as lubricant secretion and the release of degradative matrix-metalloproteinases as induced by the cytokine interleukin-1 (IL-1), the latter indicating a link between mechanotransduction and the inflammatory environment of OA. The first goal of this dissertation was to further elucidate FLS mechanotransduction by characterizing the upstream response of FLS to fluid shear and determine the influence of IL-1 thereupon. The work presented herein demonstrates for the first time a robust calcium signaling response of FLS to fluid shear, a key upstream event in the mechanotransduction of physical stimuli. Key aspects of this response were significantly altered by pre-exposure to IL-1, indicating a pathologic modulation of normal mechanosensing in the OA environment. This effect was observed across bovine and human models and was found to be potentiated by both increasing intercellular communication and modulation of cell primary cilia. In addition to chemical factors such as cytokines, the degradation of cartilage during OA produces a physical factor that perpetuates disease state in the form of cartilage wear particles (CWP). These particles are released into the synovial fluid and attach directly to the synovium. We have previously shown that CWP induce FLS monolayers to release pro-inflammatory mediators of OA. The second goal of this dissertation was to investigate the effect of CWP on both cell-level function and tissue-level properties. To this end we showed first that CWP modulate the calcium signaling response of FLS to fluid shear in a contact dependent manner, and that inhibition of intercellular communication is a potential mechanism of this effect. In areas of the articulating capsule where apposing tissues slide in direct contact with each other, contact-induced shear stress provides another relevant physical stimulus to FLS. In this case of direct interaction between surfaces, the tissue-level frictional properties may affect the magnitude of shear stress presented to the cells within the intimal layer and thus influence mechanotransduction. A novel bioreactor was developed to characterize the effect of sliding contact on downstream functions of FLS within explant tissues. An increase in metabolic activity with culture under these conditions suggests that contact shear is a relevant stimulus for FLS. While previous work has characterized synovium friction properties in sliding contact against glass, relatively little is known of synovium tribology in native tissue configurations, or the influence of pathologic conditions such as CWP attachment. This dissertation reports for the first time low friction properties for synovium against other tissues within the joint such as cartilage and demonstrates a significant deleterious effect of CWP on these properties. The research presented in this dissertation further elucidates the processes of normal synoviocyte mechanotransduction, and by demonstrating that key chemical and physical factors of the OA environment modulate both cell and tissue-level functional properties, sheds light on the mechanisms by which the synovium contributes to disease progression. This sets the foundation for future work into synovium mechanotransduction of distinct physical stimuli and the relationship with tissue-level mechanical properties, and points towards clinical interventions that seek to restore the normal mechanical environment of the joint.

Tsang Kam Wing, Edwin. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 145-151). / Abstracts in English and Chinese ; questionnaire also in Chinese. / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter CHAPTER2 --- LITERATURE REVIEW --- p.6 / Anatomy and Physiology of Knee --- p.6 / Anatomy and Physiology of Knee Osteoarthritis --- p.8 / Clinical KOA in Older Persons --- p.10 / Consequence of Clinical KOA --- p.13 / Management of Clinical KOA --- p.15 / Role of Knee Exercise in Clinical KOA --- p.18 / Goal of Treatment of Clinical KOA --- p.18 / Function of Knee Exercise --- p.18 / Physiological and Psychological Effect of Knee Exercise --- p.21 / Knee Exercise for Clinical KOA --- p.23 / Knee Exercise for Older Persons --- p.25 / Role of Health Education for Treatment of Clinical KOA --- p.27 / Community Nurse-Led Care for Clinical KOA --- p.29 / Nurse-Led Care in Community --- p.31 / Summary --- p.37 / Chapter CHAPTER 3 --- method --- p.39 / Aim and Hypotheses of the Study --- p.39 / Aim of the Study --- p.39 / Objectives of the Study --- p.40 / Null Hypotheses --- p.40 / Research Design --- p.42 / Diagnostic Criteria of Clinical KOA --- p.43 / Sample --- p.44 / Inclusion Criteria --- p.45 / Exclusion Criteria --- p.45 / Sample Size --- p.45 / Sample Recruitment --- p.47 / Intervention: community nurse-led protocol for clinical KOA --- p.48 / Treatment group --- p.49 / Control Group --- p.50 / Data Collection Procedure --- p.54 / Pre-test Assessment --- p.54 / Post-test Assessment --- p.55 / Outcome Measures --- p.56 / Disease-Specific Health Status Assessment: Western Ontario and McMaster Universities Osteoarthritis Index: Hong Kong VA 3.0- Cantonese ( WO MAC) --- p.56 / Score management and Interpretation --- p.58 / General health status assessment: the Chinese ( HK) Version of the Medical Outcome Survey ( MOS SF-36 ) --- p.60 / Score management and Interpretation --- p.62 / Specific physical function Assessment --- p.68 / Chair Rising --- p.68 / Timed performance test of mobility --- p.68 / Data Analysis --- p.69 / Ethical Consideration --- p.70 / Chapter CHAPTER 4 --- RESULTS --- p.71 / Subjects Characteristics --- p.71 / Demographic Profile --- p.72 / Baseline Assessment --- p.77 / Normality of Study Outcome --- p.84 / "Treatment Effect on WOMAC, MOS SF-36 and Specific Physical Function" --- p.86 / Disease-specific health status ( WOMAC) --- p.86 / General health status (MOS SF-36) --- p.88 / MOS SF-36 Reported-Health Transition --- p.93 / Specific Physical Function Performance --- p.95 / Chair-rise --- p.97 / Comfort-walk --- p.98 / Fast-walk --- p.99 / Documentation of the Treatment Process --- p.99 / Summary --- p.103 / Chapter CHAPTER 5 --- DISCUSSION AND CONCLUSION --- p.104 / Disease-specific Health Status --- p.106 / General Health Status --- p.108 / Pain and Physical Function Performances --- p.111 / MOS SF-36 Versus WOMAC --- p.114 / Service Collaboration --- p.118 / Effectiveness of the Protocol --- p.121 / Limitation --- p.125 / Recommendations and Implications for Future Studies --- p.133 / Implication to Practice --- p.139 / Conclusion --- p.142 / REFERENCES --- p.145 / APPENDIX I --- p.152 / Community Nurse-Led Protocol for Clinical Knee Osteoarthritis in Older Persons --- p.152 / HEALTH EDUCATION --- p.154 / Home Exercise --- p.154 / Daily Activities Involving the Knee Joints --- p.154 / Sitting and Stretching Exercise --- p.155 / Strengthening Exercise --- p.156 / APPENDIX II --- p.159 / Community Nurse-Led Protocol for Clinical Knee Osteoarthritis in Older Persons ( Chinese ) --- p.159 / 骨關節炎家居運動治療的健康教育 --- p.160 / 家居運動治療須知 --- p.160 / 影響膝蓋關節的日常活動包括 --- p.161 / 坐式伸展運動練習 --- p.161 / 張力運動練習 --- p.164 / APPENDIX III --- p.167 / Western Ontario and Mcmaster Universities Osteoarthritis Index： Hong Kong 226}0ؤ ( Questions in English ) --- p.167 / APPENDIX IV --- p.171 / Western Ontario and Mcmaster Universities Osteoarthritis Index： Hong Kong - Cantonese --- p.171 / APPENDIX V --- p.178 / Medical Outcome Survey SF-36 (MOS SF 226}0ؤ 36) ( English Version ) --- p.178 / APPENDIX VI --- p.184 / 簡明健康狀況調查表（MOS SF-36) --- p.184 / APPENDIX VII --- p.190 / Community-Based-Care of the --- p.190 / Usual Home-Help Teams --- p.190 / APPENDIX VIII --- p.192 / """Information on Right & Obligatiońح and" --- p.192 / """Consent Form""" --- p.192 / APPENDIX IX --- p.203 / Research Schedule --- p.203 / APPENDIX X --- p.205 / Letter for Institutional Approval for the Study --- p.205

"January 2003" Errata slip inserted inside front cover. Includes bibliographical references (leaves 282-313)

Osteoarthritis and ageing have been shown to induce changes in the number and health of peripheral mechanoreceptors. Whilst position and movement awareness in the osteoarthritic knee have been studied extensively, little work to date has been produced on muscle force awareness in this subject group. Poor force acuity may contribute to muscle and joint pain and dysfunction, and additionally hinder rehabilitation efforts in an osteoarthritic population. Overestimation of the muscles forces required for a given task, resulting in greater joint compression forces, may aggravate and inflame osteoarthritic symptoms. Underestimation of required muscle forces may amplify existing joint instability, increasing the risk of injury in an osteoarthritic population. Additionally, both under and overloading of muscles during the rehabilitation process can delay the return to full function after injury.When regarding the neurological process of force coding, current debate centres on the relative importance of centrally generated motor command mediated 'sense of effort' versus the peripheral mechanoreceptor signalled 'sense of tension' as the dominant coding process, with central mechanisms favoured in the majority of studies published to date. The purpose of this study was to investigate muscle force awareness in the knee extensors and flexors and hands of subjects with and without knee joint osteoarthritis. Twenty one subjects with knee joint osteoarthritis and 23 age and gender matched subjects with no known knee pathology were evaluated. All subjects performed ipsilateral isometric force estimation and force matching tasks, at levels scaled to individual maximum voluntary capacity (MVC). Errors in estimation and matching acuity were normalised to reference targets (comparison force/reference force) giving a relative score (RS) to allow comparison across submaximal force levels with RS less than 1.0 indicating that subjects produced insufficient force and vice versa.Maximal voluntary capacity tests revealed significantly lower (p<0.05) peak knee extension torque (111.2 Nm versus 145.3 Nm), but similar peak knee flexion torque (46.1 Nm versus 45.4 Nm for osteoarthritis and control subjects respectively). A pattern of overestimation at low reference levels and underestimation at high reference levels was demonstrated by all subjects. In the lower limb, force appreciation differed significantly between muscle groups regardless of knee condition, with knee extensors demonstrating greater overall accuracy than knee flexors. There was a significant difference (p<0.05) in force estimation ability and a trend to significance (p=0.066) for force matching acuity across groups at the 10% MVC test level. A significant (p<0.05) group difference in grip force estimation ability between the lowest and highest target levels was demonstrated.It can be concluded that there are small differences in force acuity in osteoarthritis subjects at lower submaximal force targets when compared to healthy age matched peers. The notion of information redundancy, whereby no new proprioceptive inputs, regardless of origin, are able to effect an improvement in force acuity in a given situation has been demonstrated in previous studies that reported relatively stable force matching acuity at forces between 30% and 60% of maximal capacity. The poor comparative force perception demonstrated in this study by the osteoarthritis group at the lower submaximal test levels supports the notion that centrally generated copies of motor commands do not provide sufficient data to adequately encode force magnitude at low levels of force generation, evoking a greater reliance data received from peripheral mechanoreceptors. This has significant implications for this subject group given that the majority of daily tasks require only low levels of force generation. Given that perceptive acuity in a variety of sensory modalities has been shown to improve with training there may be a role for force perception training in older adults with osteoarthritis.

The principal aim of this thesis was to develop and implement a standardised protocol for the fractal analysis of cancellous bone architecture. Cancellous bone structure from different skeletal sites in groups of osteoporotic, osteoarthritic and normal individuals was analysed. The results of fractal analysis were explained in the context of conventional bone histomorphometry and a priori knowledge to advance the understanding of cancellous bone architecture. There has been much effort devoted to the pursuit of descriptors of cancellous bone complexity. The aim of these endeavours has been to develop morphological descriptors of bone quality that explain the functional properties of the cancellous bone structure for age-related changes, the effect of disease processes or the effect of therapeutic agents on the diseased skeleton. The fractal analysis of the complexity of cancellous bone architecture promises to be an exciting addition to existing analytical techniques. The establishment of a standardised methodology for the fractal analysis of cancellous bone encompassed many components. Knowledge of the stereological and histomorphometric principles that are employed in currently available techniques enabled a comprehensive examination of the factors that effect the measurement of the fractal dimensions. The methodology presented in this thesis has been optimised specifically for measuring sectional fractal dimensions in histological sections of cancellous bone. The sectional fractal dimensions show that, over three ranges of scale, cancellous bone is effectively fractal at multiple sites in the normal skeleton. The three sectional fractal dimensions describe different morphological compartments of the cancellous bone structure. Fractal 1 describes the surface texture of the trabeculae, fractal 2 describes the shape or form of individual trabeculae and fractal 3 describes the spatial arrangement or overall architecture of the cancellous bone. This thesis reports that in the normal skeleton there are differences between skeletal sites for the fractal dimensions, which are dependent on the functional properties of the skeletal sites. Fractal 2 and fractal 3 for subchondral cancellous bone is greater than vertebral body and iliac crest cancellous bone, which indicates greater morphological complexity. Also, fractal 2 and fractal 3 in subchondral cancellous bone show an age-related decrease, which suggests that the cancellous bone structure becomes less complex with age. This interostotic variability in response to ageing is indicative of the heterogeneity in functional properties of cancellous bone in the skeleton. In this thesis, fractal analysis has been shown to detect morphological differences in the cancellous bone between normals, osteoporotics and osteoarthritics in the compressive and tensile trabeculae of the femoral head and the iliac crest. These data have provided new insights into the mechanisms of change to cancellous bone structure in ageing and in disease. Age-related changes in the structural parameters of cancellous bone are seen at all the skeletal sites in the normals but are only present in the compressive trabeculae of the femoral head in the osteoporotics and not at all in the osteoarthritics. These observations indicate that these disease processes are associated with an uncoupling of the control mechanisms that affect cancellous bone structural complexity. In the normals, the fractal dimensions only show age-related change in the tensile trabeculae of the femoral head, suggesting that fractal analysis is not suitable for detecting the age-related changes that are quantified by the structural parameters of cancellous bone in these study groups but the fractal dimensions detect underlying cancellous bone complexity independent of age. For the osteoporotics, fractal 1 is the same at all skeletal sites. This suggests that the relative levels of remodeling activity are the same for both normals and osteoporotics. Fractal 2 for both the compressive and tensile trabeculae in the femur is significantly lower for the osteoporotics than the normals but in the iliac crest, fractal 2 is the same. This implies that in the femoral head the osteoporotics have trabeculae that are significantly less complex in shape than the normals. This phenomenon is not seen in the iliac crest, which is usually the site of diagnostic biopsy. Therefore, biopsies for diagnosis of osteoporosis may not show changes in cancellous bone structural complexity that are evident in disease affected sites. The structural parameters of cancellous bone show that osteoporotics lose whole trabeculae due to perforation of trabeculae, through decreased Tb.N and increased Tb.Sp. This leads to less interconnection between trabeculae, loss of branching and more rounded trabeculae, hence the trabeculae are less complex in shape. For fractal 3, in compressive and tensile regions of the femur the osteoporotics are significantly lower than the normals and in the iliac crest the osteoporotics are the same as the normals. This indicates that in the femoral head the spatial arrangement of the trabeculae within the cancellous structure of the osteoporotics is less complex. The structural parameters of cancellous bone show that there is loss of whole trabeculae, which is associated with increased spatial separation between the trabeculae as bone is lost. For the osteoarthritics, fractal 1 is the same as the normals at all skeletal sites. Fractal 2 for the compressive trabeculae in the femoral head is significantly higher for the osteoarthritics than the normals but in the tensile trabeculae of the femoral head and the iliac crest fractal 2 for the osteoarthritics is the same as the normals. This implies that in the compressive trabeculae of the femoral head the osteoarthritics have trabeculae that are significantly more complex in shape than the normals. The structural parameters of cancellous bone show that the compressive trabeculae of the femoral head are thicker, more numerous and less widely separated with greater BV/TV than the normals. This leads to greater interconnectivity between trabeculae and more complex branching, hence the trabeculae are more complex in shape. For fractal 3, in the compressive and tensile regions of the femoral head the osteoarthritics and the normals are the same but in the iliac crest the osteoarthritics are lower than the normals. This indicates that the spatial arrangement of the trabeculae within the cancellous structure of the osteoarthritics does not change in response to the disease process in subchondral cancellous bone adjacent to the articular lesion but in the iliac crest the spatial arrangement of the trabeculae in osteoarthritics is less complex in shape. The structural parameters of cancellous bone show that BV/TV is increased in the compressive and tensile trabeculae of the femoral head but not in the iliac crest of the osteoarthritics. This indicates that the spatial complexity of the trabecular arrangement within the cancellous structure of osteoarthritics changes independently of changes in cancellous bone structure detected by the structural parameters of cancellous bone. The sectional fractal dimensions have detected differences in morphological complexity between the normals and disease groups and between the skeletal sites. These novel data have been obtained using an innovative technique that is not dependent on assumptions based on conceptual models of cancellous bone structure. A priori knowledge of bone biology is utilised to enable the fractal analysis to measure specific morphological entities within the cancellous bone structure. The fractal dimensions have identified changes in the morphological complexity of specific components of the cancellous structure, which are not identified by existing model-based morphometric techniques. This has enabled new understanding of how change to cancellous bone structure occurs as a result of a disease process. Fractal analysis is a novel tool that will prove useful for the study of changes in cancellous bone structure due to disease and to study the use of therapies to alter or maintain the quality of cancellous bone architecture. / Thesis (Ph.D.)--Medical School, 2002.