Quantitative Three-Dimensional Assessment of Bone and Cartilage in Osteoarthritic and Normal Knees Using Novel Imaging Methods and Mechanical Indentation Testing

Osteoarthritis (OA) is a painful, debilitating disease affecting approximately three million Canadians, most commonly at the knee. In addition to joint cartilage damage, the disease is also marked by changes in the underlying bone. It has been suggested that changes in bone stiffness, thickness and density influence and accelerate the breakdown of cartilage and the development of OA. In order to verify this (i.e. understand when during the disease process these changes occur and assess their impact on the timing and extent of damage to the bone or cartilage) there is an urgent need to develop a tool that can reliably assess bone and cartilage simultaneously. The aim of James Johnston’s research is to understand early onset and progression of osteoarthritis and to develop diagnostic tools for its early detection. Johnston has already developed a novel method of matching bone to cartilage that can be used to assess cartilage and underlying bone simultaneously in any joint. He is now working on a method to investigate relationships between bone (thickness, density) and cartilage (thickness, biochemistry) using magnetic resonance imaging (MRI), computed tomography (CT) and three-dimensional assessments. He will then link information gained through these imaging methods with physical stiffness measures to determine how these properties are affected at early and late stages of OA, compared to healthy subjects. This research will improve understanding of how OA develops, and contribute to the development of methods for the early detection and treatment of the disease.

Optimizing functional ability in stroke rehabilitation

Each year, approximately 50,000 Canadians suffer a stroke—the number one cause of neurological disability leading to impaired balance and mobility. Almost 90 per cent of stroke survivors have difficulties with everyday tasks, a reduced tolerance for physical activity, a sedentary lifestyle and multiple secondary complications. Many of these complications can be reduced with rehabilitation.

As a MSFHR-funded scholar, Dr. Janice Eng researched the effectiveness of a specific exercise program in improving balance and mobility in people with stroke. Now, Dr. Eng is working to optimize the functional abilities of people with stroke through innovative and effective rehabilitation interventions. One of these treatments includes a novel, cost-effective therapy where the patient manages their own amount of therapy for the arm and hand using a self-guided program. Dr. Eng will conduct a series of clinical studies aimed at improving arm and leg function in people living with stroke. People with stroke will be invited to participate in these studies and measurements of their abilities will be evaluated before and after the treatment. Changes in their abilities will then be analyzed and compared to individuals with stroke who receive what is considered standard therapy.

The development of effective rehabilitation interventions will improve the functional abilities of people with stroke, enable participation in social roles and physical activities, reduce secondary complications, and enhance quality of life. Novel interventions can also serve as a model for rehabilitation interventions in populations with other chronic health conditions.

Links between Patellofemoral Biomechanics and Osteoarthritis

One in ten Canadians suffers from osteoarthritis, an incurable disease that causes pain and limits motion in joints. It occurs most often in the knee joint; the patellofemoral joint, which is located at the juncture of the kneecap and thigh bone, is involved in half of these cases. Emily McWalter’s research is focused on improving the diagnosis and treatment of patellofemoral osteoarthritis. It is widely believed that biomechanical factors, such as abnormal joint motion and excessive force exerted on bone and cartilage are related to the onset and progression of osteoarthritis. While treatment focuses on correcting abnormal joints through surgery or physiotherapy, these treatments do little to slow progression of the disease. That’s likely because the procedures do not correct all of the biomechanical factors contributing to the damage. With recent advances in MRI imaging, it’s now possible to study biomechanical factors and cartilage degeneration simultaneously. Emily McWalter’s research is focused on developing better methods of detecting and identifying the causes of cartilage degeneration earlier. She is currently working to develop and validate a tool that can estimate the pressure that develops on the surface of cartilage, with a view to using this information to determine if areas under abnormal levels of pressure are at greater risk for degeneration. If successful, this tool will be a valuable asset in understanding the onset and development of patellofemoral osteoarthritis and in assessing the effectiveness of surgeries and other biomechanics-based treatment strategies.

The Drainage of Cerebrospinal Fluid and Development of Inflammatory Biomarkers in Acute Spinal Cord Injury

Approximately 1,050 new spinal cord injuries occur every year in Canada, primarily in young people. There are currently approximately 40,000 Canadians living with a spinal cord injury (SCI). As a physician and neuroscientist, Dr. Brian Kwon is actively involved in discovering new ways to improve the prognosis of those with SCI. Experimental treatments that have shown tremendous benefits in animal models of spinal cord injury have not translated in human clinical trials. This discrepancy suggests important differences in the biological responses to spinal cord injury between humans and animals. Within minutes of a spinal cord injury occurring, the spinal cord swells at the injury site. This swelling reduces blood flow and oxygen to the spinal cord tissue and can subsequently result in further secondary damage. Dr. Kwon is researching whether draining some of the cerebrospinal fluid (CSF) that surrounds the spinal cord will reduce the pressure on the cord, restoring blood flow and minimizing the risk for secondary damage. In a clinical trial of patients enrolled at Vancouver General Hospital within 48 hours of their SCI, CSF samples will be taken and measured for proteins that regulate inflammation. This biochemical evaluation will offer the first human description of how these inflammatory proteins are expressed following injury, leading to new biomarkers or indicators of injury severity to assist with further research. The expression proteins will be compared with the expression of proteins in animal models to determine differences in response between humans and animals. Ultimately, these insights will assist researchers in developing therapies to improve the lives of patients with spinal cord injuries.

Action Schools! BC: The effect of a school based physical activity model on risk factors for cardiovascular disease in Aboriginal children

Cardiovascular disease (CVD) is a chronic condition that can lead to heart attack and stroke. CVD costs the BC health care system approximately $2.5 billion a year. Sadly, the onset of cardiovascular disease often starts in childhood. About 50 per cent of North American children exhibit one or more risk factors for CVD and many children and adolescents exhibit multiple risk factors. These statistics are worrisome because the severity of CVD increases with the number of risk factors, and risks during childhood tend to track into adulthood. As a result, these children are susceptible to developing cardiovascular disease as adults. Previous research has linked higher levels of physical activity during childhood to a lower risk for CVD as adults. Lindsay Nettlefold is examining the prevalence of CVD risk factors in children and whether differences exist between girls and boys and between children of different ethnicity. She is also studying whether a school-based physical activity program can reduce the level of risk factors for cardiovascular disease in children. The goal to develop an effective program that could be used to improve cardiovascular health in children will prove beneficial in helping to prevent the development of disease later in life.

Genetics of alopecia areata

Alopecia areata (AA) is a common autoimmune disease leading to extensive hair loss in men, women and children. About 640,000 Canadians (one out of 50) will develop AA. There is no cure, and treatment options are minimal. While, in general, the condition is not life threatening, hair loss can be psychologically devastating, particularly for women and children. Using a rat model, Dr. McElwee has identified several areas on chromosomes where genes coding for AA susceptibility are present. Now further work is required to determine the specific genes involved and what they do. Once these genes are identified in the rat model, the next step is a large scale study to identify corresponding genes in AA-affected humans. A more comprehensive understanding of the structure and function of these genes in comparison to corresponding genes in non-affected individuals will lead to a better understanding of how AA develops. In the long run, the goal is to explore the development of treatments which specifically target and ameliorate the affects of underlying genetic flaws that give rise to the disorder.

Evaluating the contribution of bone micro-architecture, density and bone strength to fracture at clinically relevant sites using a novel instrument:An Xtreme CT study

Osteoporosis is a chronic condition whereby bones become fragile and individuals are predisposed to fracture. Osteoporosis may occur in all older people but it most frequently affects post-menopausal women. Worldwide, more than nine million osteoporosis-related fractures occur annually. Older Canadians sustain more than 24,000 hip fractures annually — which levies a substantial physical, emotional and economic burden on individuals and the health care system. By 2040, this number is expected to increase to 90,000 at a cost of $2.4 billion. The likelihood of a person sustaining a fracture is related to their bone strength and their propensity to fall. Bone strength is related to bone’s material and structural properties. Currently, DXA (dual-energy x-ray absorptiometry) is the most commonly used diagnostic tool to measure bone health. However this technology has limitations in that it provides a two-dimensional (2-D) representation of bone, a 3-D structure. Further, DXA does not capture the nuances of bone geometry and structure that underpin bone strength. Recently, a high resolution imaging system (the Xtreme CT scanner) was developed that is able to assess bone mass, geometry and bone microarchitecture. The extent to which this novel technology is able to predict bone failure is currently unknown. Thus, Sarah Braid will utilize state-of-the-art imaging techniques (X-treme CT and pQCT) to evaluate bone strength and its components – and most importantly – link these evaluative tools with the susceptibility of a bone to fracture. The results of her research will enhance our ability to assess fracture risk so as to prevent fractures in vulnerable populations in future.

The characterization of KiSS1 and GPR54 in breast cancer and other hormonally responsive cancers

Cancers whose growth is influenced by sex hormones, such as estrogen and testosterone, form the largest group of cancers that affect Canadian men and women. Breast cancer remains the second most common cause of cancer death among women in North America, and prostate cancer rates third for men. While there have been advances in treatment, many of these patients will succumb to their disease when tumors metastasize (spread to other organs or tissues in the body). The KiSS1 and GPR54 genes have demonstrated the ability to prevent metastases from developing. While the importance of KiSS1 and GPR54 are being studied in other cancers, little has been done to investigate the involvement of these two genes in clinical breast and ovarian cancers, and no studies have been conducted in prostate cancer. Building on her MSFHR-funded Master’s research, Leah Prentice is investigating whether KiSS1 and GPR54 have dual roles as both tumor promoters, via their involvement in hormonal processes, and also as suppressors of metastasis. By understanding the anti-metastatic mechanism of these two genes, Prentice hopes to contribute to the development of more targeted therapies and diagnostic tests that would allow for earlier detection of these potentially life-threatening cancers.

Novel strategies for treatment of PTEN deficient prostate cancer

Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men of the Westernized world. While early stage disease is frequently curable with surgery or radiotherapy, limited treatment options are currently available for approximately one-third of patients who clinically present with locally advanced or metastatic disease resulting in a poor prognosis for patients with advanced disease. One treatment option that is currently being used for advanced PCa is a medical procedures designed to block androgenic steroids to induce death of prostate cancer since prostate cancer cells typically require these hormones for their growth and integrity. While this treatment is often effective with a response rate of up to 80%, within 1-3 years the tumours inevitably recur as hormone-refractory variants, a condition for which there is no current effective therapy. Thus if we are to have an impact on survival rates of patients with PCa, new therapeutic strategies are required for treating advanced disease. Up to 50% of advanced prostate cancers have acquired mutations in a gene called PTEN that essentially inactivated it. Inactivation of PTEN in prostate cancer is correlated with a poor prognosis. Loss or inactivation of this gene makes prostate cancer cells more resistant to different forms of therapy including chemo-, radiation and hormone-therapy. The development and progression of cancer is dependent on the deregulation of the intricate balance in the rates of cell growth and death. The proposed project addresses how loss of the PTEN gene confers cell with a survival advantage and resistance to therapies. Under ordinary conditions, PTEN keeps growth of normal cells in check by serving as a brake to inhibit cell growth. When PTEN is mutated in cancer, the brakes fail and this confers uncontrolled growth and increased resistance of the cancer cells to chemotherapy and hormone ablation therapy. My lab is actively working on how loss of PTEN protects prostate cancer cells from death signals and we are looking for different ways to block the effects of inactivating PTEN. Results of this study will be directly relevant to development of new therapies aimed at treating the subset of advanced prostate cancers that have lost PTEN.

Wheelchair use by nursing home residents: An exploration of the relationship between wheelchair use, activity participation and quality of life

It’s been estimated that more than half of nursing home residents use wheelchairs as their primary means of mobility. But little research has examined wheelchair use within facility settings. A few studies have shown that nursing home residents experience a variety of wheelchair-related problems, such as wheelchair discomfort, immobility, poor posture, and dysfunctional wheelchairs. As well, rather than facilitating independence, wheelchairs may be used as restraints. William Mortenson is conducting a two-phase study on wheelchair use in nursing homes. In the first phase, Mortenson will explore the overall impact of wheelchairs and wheelchair seating on nursing home residents through interviews and observations. In the second phase, he will identify factors that predict wheelchair mobility and investigate the relationship between wheelchair use, activity participation and quality of life amongst nursing home residents. He has three goals for the study: to improve understanding of how the nursing home setting influences the availability of wheelchair equipment and impacts the use of wheelchairs; to improve opportunities for residents to access wheelchairs; to support lobbying for better funding for wheelchairs and wheelchair services. He also hopes his research will ultimately contribute to the health and quality of life of facility residents through the development of an intervention program, which could improve wheelchair-related institutional policies and practices for this increasing segment of the population.