Dissertation submitted in partial compliance with the requirements for the Master's Degree in Technology: Homoeopathy, Technikon Natal, 1997. / This clinical trial focused on evaluating homoeopathic simillimum treatment of hand osteoarthritis. Emphasis was placed on assessing changes in measurable clinical manifestations and participants pain perception related to this condition. A double-bl ind, placebo-controlled protocol was uti 1ized involving 30 participants chosen from respondents to advertising in the Durban newspapers. Participants were randomly assigned to receive homoeopathic simillimum or placebo treatment. Bilateral antero-posterior-, oblique- and lateral hand and wrist x-ray's were taken to diagnose osteoarthritis. Clinical evaluation utilized the following tools: 1. Collin dynamometer (hand grip-strength) 2. Finger goniometer (degrees of mobility) 3. Circumeter (joint circumference measurements) 4. Aesthesiometer (articular index of joint sensitivity) The lOl-point Numerical Rating Scale (Jensen et al. 1986) was used to test pain intensity and the Short Form McGi 11 pain questionnaire (Melzack 1987) was used to monitor participants pain perception. All tests and questionnaires were repeated monthly over the three month trial duration . / M

A dissertation presented in partial compliance with the requirements for the Masters Degree in Technology: Chiropractic, Technikon Natal, 2001. / Osteoarthritis (OA) is a disease that is localized to diarthodal joints and is characterized by degeneration of hyaline cartilage, with secondary changes in the peri-articular bone and soft tissue. OA is considered to be a sequale of traumatic and age respondent degenerative changes which result in loss of cartilage and impairment of function. The purpose of this investigation is to evaluate the relative efficacy of Action Potential Therapy, Transcutaneous Electrical Nerve Stimulation and placebo in the treatment of Osteoarthritis of the knee. This was a prospective, randomized clinical trial consisting of sixty patients who volunteered from the greater Durban area. The patients diagnosed as having Osteoarthritis of the knee, were randomly divided into four treatment groups. Group one and two consisted of twenty patients each and group three and four consisted often patients each, all between the age of 40 - 65 years old. Group one received Action Potential therapy (APT); group two received Transcutaneous Electrical Nerve Stimulation (TENS); group three received placebo APT and group four received placebo TENS. For statistical analysis parametric and non-parametric tests were used in all hypothesis Data capturing took place for all groups at the 1st, 2nd and 4th consultations. Subjective data was collected using the Numerical Pain Rating Scale-l Ol ; McGill Pain Questionaire and Western Ontario and MacMaster Universities Index (WOMAC). Objective data was gathered using the algometer and goniometer. / M

Osteoarthritis (OA) is the most common degenerative joint disease affecting more than 40% of people above the age of 65 (Neogi et al., 2013). Obesity is one of the main risk factors of OA and has become a major problem in Western societies. With sedentary lifestyle and the aging of the population, it is estimated that more than 50% of British adults will be obese in 2030 (Wang et al., 2011). So far, the effect of obesity on joint degeneration has primarily been explained by the increased load on the joints. However, a growing number of studies have revealed that adipose tissue can affect cartilage and other joint tissues at a molecular level. The main goal of this thesis was to investigate the role of local knee joint tissues in obese patients with OA. The expression of molecular markers was investigated in local knee tissues: cartilage, synovium, infrapatellar fat pad (IPFP) and subchondral bone collected during Total Knee Replacement (TKR). A range of techniques (RT-PCR, Real Time qPCR, WB, IHC/ICC and ELISA) was used to examine the differences between genes and proteins expression in both lean and obese patients with OA. Further, the local immune cell infiltration was investigated in knee adipose tissue depots (synovium and IPFP) using flow cytometry. In addition, the subchondral bone microstructure was analysed using micro-Computed Tomography (μCT) and IHC techniques. Chondrocytes from OA patients were found to express a range of obesity-related genes. ADIPOR1 was produced significantly higher than ADIPOR2 in OA chondrocytes. Furthermore, CCL2 was produced at higher while PPARγ and visfatin were produced at a lower level in obese patients’ chondrocytes in comparison to lean ones. Synovium and IPFP also expressed a range of obesity-related genes. PPARγ and visfatin expression was lower in obese synovium and IPFP in comparison to lean. Surprisingly, adiponectin was expressed at a significantly lower level in obese patients’ synovium. In contrast, adiponectin was not differently expressed in lean and obese patients’ IPFP. The IPFP was found to be a significantly higher producer of PPARγ and adiponectin in comparison to synovium. Synovium, on the other hand, has an increased expression of VCAM-1, TLR4 and CCL2 in obese patients. An increased number of macrophages (defined by CD45+CD14+ and CD14+CD206+ markers expression) was detected in the synovium and IPFP from obese OA patients. Furthermore, there was an increased number of CD86+CD14+ cells in the synovium from obese patients. Other macrophage-related proteins including HLA-DR, CD36 were also expressed at a higher level in synovium from obese patients. T-lymphocyte detection revealed a higher number of CD3+CD4+ T cells in the synovium (but not IPFP) from obese patients but no change in the CD3+CD8+ population in both the synovium and IPFP. Subchondral bone analysis revealed possible differences in this tissue in obese male patients with OA in comparison to lean patients. μCT examination of subchondral bone showed a significantly lower bone mineral density (BMD) in obese in comparison to lean male OA patients. IHC analysis of bone sections suggested that there was an increased number of bone marrow adipose tissue macrophages. In addition, osteoblasts obtained from obese OA donors expressed a significantly higher level of ADIPOR2 and lower level of PPARγ mRNA in comparison to lean patients’ osteoblasts. The data obtained suggests that there were differences between lean and obese patients with OA at a molecular level. This proposes possible future directions for targeting these diseases. The limitation of the study were as follows: 1) possible different stages of end-stage OA between analysed patients, which could lead to differences in obtained data, 2) no non-OA control samples included in the study. However, the presented study may suggest that all tissues in the knee joint contribute to the interplay between OA and obesity. In addition, the data obtained is the first to suggest that there are differences in gene and protein expression in the synovium and IPFP from the same donor. Furthermore, there are differences in the immune cell populations in local adipose tissue depots (synovium and IPFP) from OA joints, which are linked to obesity. All of this data has helped to increase our understanding of the interaction between obesity and OA.

The burden of osteoarthritis continuous to increase. While joint replacement surgery provides a cost effective and efficacious treatment for end stage osteoarthritis, no treatment exists to prevent or slow the progression of the disease. Understanding the cellular and molecular changes in the synovium following trauma and in early osteoarthritis could facilitate the identification of novel therapeutic targets. Previous studies identified synovial hyperplasia following intra-articular fractures, cartilage injury and in osteoarthritis. In mice, proliferation of synovial mesenchymal stromal/stem cells (MSCs) leads to synovial hyperplasia following joint surface injury. The driver for this expansion of MSCs in the synovium is unknown. Recently, YAP, a key downstream effector of the Hippo pathway, has been shown to causes tissue overgrowth due to modulation of MSC proliferation. The joint surface injury model of osteoarthritis was used to investigate whether YAP may play a role in synovial hyperplasia following joint surface injury. This work shows that synovial hyperplasia is common to both healer and non-healer mouse strains after joint injury and that Yap expression is up regulated on a protein and mRNA level. Using the same injury model in a mouse with a conditional knockout of Yap in Gdf5 lineage cells, showed that a Yap knockout in Gdf5 progeny cells prevented hyperplasia of synovial lining after joint surface injury, suggesting that YAP is required for MSCs in the synovium to proliferate. In patient synovial samples, YAP expression was up regulated in activated synovium, including a subset of CD55 positive fibroblast-like synoviocytes in the synovial lining. Proliferating cells were positive for active YAP. This suggests that findings in our mouse model are clinically relevant. Furthermore, modulation of YAP and synovial MSC proliferation after JSI provides a means to study the role of synovial hyperplasia after trauma. This could lead to a potential novel therapeutic target for the treatment of posttraumatic osteoarthritis.

Knee joint osteoarthritis is recognised as a significant subset of osteoarthritis. Little work has examined muscle changes that occur with knee joint osteoarthritis. Much of this work has centred on strength deficits, while little work has examined the effect of joint pathologies, such as osteoarthritis, on the fatigue resistance of the muscles associated with an affected joint. The purpose of this study was to investigate the relative fatigue-resistance characteristics of the vastus medialis in subjects with and without knee joint osteoarthritis, as well as the ability to predict endurance times in these groups, using high spatial resolution electromyography and a sub-maximal isometric endurance test. Twenty-six subjects with unilateral knee osteoarthritis and seventeen subjects with no known knee pathology were evaluated. All subjects performed initial tests to evaluate maximum voluntary contraction (MVC), voluntary activation levels, and true maximum force (TMF). Endurance time was assessed during an isometric quadriceps contraction at 50% of the true maximum force. Surface electromyography (sEMG) data was collected from the vastus medialis muscle of the quadriceps group during the endurance test. MVC tests showed that the affected leg of the group with osteoarthritis was significantly weaker (p < 0.05) than the unaffected leg. Voluntary activation data showed that subjects with osteoarthritis presented with significant bilateral deficits (p < 0.05). TMF data showed a significantly lower (p < 0.05) true potential for force generation in the affected compared to the unaffected leg of the osteoarthritis group. Endurance time data showed no significant difference between groups. Electromyography data showed significant differences (p < 0.05) between the affected and unaffected legs in initial values of Median Frequency (MDF), Mean Power Frequency (MPF) and Conduction Velocity (CV), the percentage change in CV and the relative rate of change in the frequency band between 5 and 30Hz (FB1). Finally, significant correlations were seen between endurance time and the relative rate of change of MDF, MPF and CV calculated over the initial thirty seconds of the endurance test. There were no significant correlations from either leg of the group with knee joint osteoarthritis.It can be concluded from this study that there are differences in strength measures, and in the sEMG signal collected from the vastus medialis muscle of the affected and unaffected legs of subjects with knee osteoarthritis. It appears likely that the differences observed in the sEMG signals were related to a decrease in the representation of type-2 muscle fibres in the vastus medialis of the affected leg. Furthermore, these changes in the behaviour of the signal appear to indicate an improvement in the relative fatigue resistance of the affected leg in relation to the unaffected leg of the group with knee osteoarthritis.Moderate success was seen with the prediction of endurance time in control subjects in the current work using a short duration (30-second) endurance test. This relationship was not seen in either the affected or unaffected leg of the subjects with knee osteoarthritis. Further investigation utilising different sEMG collection and analysis techniques in this area may improve prediction of endurance time in unaffected and affected subjects.

Background : The oral administration of Glucosamine and intra-articular (IA) injection of Hyaluronic Acid were used to treat osteoarthritis. Several studies supported that clinical pain symptoms could be alleviated, and activities of daily life improved after the completion of IA knee hyaluronic acid injections. However, the efficacy of oral administration of Glucosamine was inconclusive. In Taiwan, the Taiwan's National Health Insurance (NHI) made the strict formulations for the both of ¡§oral administration of Glucosamine ¡§and ¡§IA knee hyaluronic acid injections.¡¨ But, there were no evidence to prove that whether the combined treatments from both oral administration of Glucosamine and IA knee hyaluronic acid injections were more effective than the treatment with the IA knee hyaluronic acid injections alone. Objectives : The porpose of this study was to examine whether the effects of treatment combined with both ¡§oral administration of Glucosamine and IA knee hyaluronic acid injections¡¨ on clinical pain symptoms and activities of daily living were better than ¡§IA knee hyaluronic acid injections¡¨ alone. Methods : We randomly assigned 60 patients with symptomatic knee osteoarthritis, at the department of Orthopedics, Kaohsiung Municipal Union Hospital, between 2008 and 2009, to receive oral administration of Glucosamine and IA knee hyaluronic acid injections or oral administration of Placebo and IA knee hyaluronic acid injections. In this study, clinical pain symptoms, and activities of daily living were assessed by using Lequesne's Index, visual analogue scale index, Berg Balance Test, and Biodex Balance Test before and after the treatment in 60 patients with the knee OA. Result : The mean age was 66.6 years, and 70 percent were woman. There was a significant efficacy before and after treatments both in the treatment group(p<0.001) and the placebo control group(p<0.001). In the other hand, there was not the statistical significance in the efficacy between the treatment group and the control group(p=0.869). Conclusion : The combined treatment with both oral administration of Glucosamine and IA knee hyaluronic acid injections was not significantly better than the IA knee hyaluronic acid injections alone in reducing knee pain or promoting the function of daily life.

Thesis (M.S.M.E.)--University of Delaware, 2009. / Principal faculty advisor: Jill S. Higginson, Dept. of Mechanical Engineering. Includes bibliographical references.

Objective: To investigate the effectiveness of glucosamine for knee osteoarthritis (KOA) through the examination of symptomatic and structural effectiveness of the compound, and to increase public awareness, especially in Hong Kong, about its potential benefits contingent upon the quality of the existing research. Methods, Results: All studies published between 1965 and 2011 in MEDLINE, and from 1980 to 2012 in EMBASE, which evaluated the effectiveness of glucosamine for KOA, were searched and identified using specific keywords. A total of 9 randomized controlled trials out of 672 articles from MEDLINE and 1712 articles from EMBASE were included in this systematic review. The included studies used different outcome measures to compare the effects of glucosamine with other remedies for treating KOA. Similar demographic and clinical characteristics of the subjects between the intervention and the control groups were recorded. The studies were from eight countries. The average age of the subjects in the nine studies were 55 years and they were generally overweight. Though there were discrepancies among the results generated in the included studies, the potential benefits of glucosamine could not be dismissed. Discussion: Factors about compliance, possible drug-to-drug interaction, unknown placebo, subject characteristics (disease progress and severity, age, gender, and occupation), as well as the dosage of glucosamine could have greatly affected the results of the included studies. Limitations on finding articles about the effectiveness of glucosamine for OA of different sites, the cost-effectiveness of the compound, the assumption of the language restriction, and the risks of biases were raised. More clinical trials with comprehensive considerations of all possible factors affecting the results, are necessary. Conclusion: Based on this systematic review, the potential effects of glucosamine for KOA remain unclear. More research of different ethnic groups, especially of people in Hong Kong, is needed to raise public awareness about the effectiveness of glucosamine for OA other than the knee globally as well as in Hong Kong. / published_or_final_version / Public Health / Master / Master of Public Health

Osteoarthritis (OA) has been one of the most prevalent joint disorders which cause pain, impair mobility of patients and bring heavy burden to social economics. Unfortunately up to now we still know little about OA. We are not sure what exactly cause OA. The pathogenesis of OA is not clearly understood. Besides, we don’t have effective treatment for OA. When joint degeneration goes to the end-stage, Total Joint Replacement surgery seems to be the only way to relieve pain and restore joint function. Since cartilage degeneration is quite difficult to be stopped or reversed, people are trying to looking into the upstream events which occurred at early stage of Osteoarthritis. Nowadays, early OA changes have drawn attention. It is considered to play an important role in OA initiation and progression and may be the key for OA treatment. However, the exact change at each component of the joint including cartilage, bone and osteochondral junction at early stage of OA is still poorly elucidated. Because it’s quite difficult to obtain information from early staged OA patients, and it’s also difficult to conduct longitudinal observation on human OA patients, we need animal models to obtain knowledge about OA. In this study, we adopted the Dunkin-Hartley (DH) strain guinea pig, which has been widely accepted as aging-related spontaneous OA model. Meanwhile, the pigmented guinea pig was used as OA-resistant control. The aim of this study was to: 1) observe and compare the difference of OA progression between DH and pigmented guinea pigs; 2) characterize the early changes of subchondral bone, cartilage and osteochondral junction in DH strain comparing with pigmented guinea pig; 3) preliminarily investigate the disease-modifying effect of Transforming Growth Factor beta 1 (TGFβ1) receptor inhibitor on OA progression. Significant cartilage degeneration was found in DH strain with cartilage surface disruption, cleft, proteoglycan loss and diffused hypertrophic chondrocytes clustering at age of 12 months. In comparison, cartilage of pigmented guinea pigs remains intact and smooth. At early stage with age from 1 to 3 months, in DH strain, subchondral bone was found to be sclerotic, denser with ultrastructure change, and chondrocytes was found with elevated level of proliferation and apoptosis concurrently, while osteochondral junction was found to be thicker, denser and less porous comparing with pigmented strain. Additionally, TGFβ1 receptor inhibitor was found effective to suppress formation of Bone Marrow Lesion, which is the early sign of OA detected by Magnetic Resonance Imaging. It also preserved the volume of cartilage and subchondral plate against OA degeneration. In conclusion, OA-prone Dunkin-Hartley guinea pigs showed significant cartilage degeneration at age of 12 months. In comparison, pigmented guinea pigs are OA-resistant. At early stage of OA, DH guinea pigs were found with subchondral bone ultrastructure change and chondrocytes hyperproliferation as well as apoptosis. Disease-modifying drugs such as TGFβ1 receptor inhibitor is potentially an option for OA treatment. The finding of this study may contribute to new insight and understanding of early OA pathogenesis and potential development of specific therapeutics strategies. / published_or_final_version / Orthopaedics and Traumatology / Doctoral / Doctor of Philosophy

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