Medicine and Health Sciences Commons^™

Assessing Inflammation In The Pathology Of Knee Osteoarthritis, Zachary J. Koudys

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) is a joint disease that causes pain, stiffness, and loss of function. Inflammation of the synovium plays a role in the pathology of OA. Macrophages are the dominant immune cells in synovial tissue. Activated macrophages over-express the translocator protein (TSPO). [¹⁸F]FEPPA is a 2^nd generation positron emission tomography (PET) tracer that can target TSPO with high specificity. Hybrid [¹⁸F]FEPPA PET/MRI may enable accurate quantification of macrophage activity in vivo. In this work, [¹⁸F]FEPPA tracer uptake in knee synovial tissue was measured ex vivo using autoradiography and was validated to correlate to …

Return To Physical Activity Post-Total Knee Arthroplasty And Total Hip Arthroplasty, Bob T. Gao, Ashley Lowndes, Denise M. Connelly

Undergraduate Student Research Internships Conference

No abstract provided.

To Develop A Clinically Friendly Multi-Segment Kinematic And Kinetic Foot Model And Test It On Pre-/Post-Hto Patients With Medial Knee Osteoarthritis And Knee Varus, Songlin Zhu

Electronic Thesis and Dissertation Repository

This study aims to develop a clinically useful multi-segment foot model that will enable the analysis of foot kinematics and kinetics in an optical motion capture laboratory setting. This study will also test the new multi-segment foot model on patients with knee osteoarthritis and varus knee alignment that is corrected by high tibial osteotomy (HTO). The multi-segment foot model divides the foot into four functional segments: the hindfoot, midfoot, forefoot and hallux. An X-Z-Y-Cardan angle rotation convention was used to determine intersegmental dorsi/plantar flexion, inversion/eversion, and internal/external rotation. Joint moments, joint powers and medio-longitudinal arch (MLA) height/length ratio were also …

Three-Dimensional Ultrasound Imaging For Characterization Of Synovitis In First Carpometacarpal Osteoarthritis, Carla Du Toit

Electronic Thesis and Dissertation Repository

First carpometacarpal osteoarthritis is one of the most common forms of OA and is a significant source of pain and disability for patients. Discrepancies between traditional imaging modalities and patient reported outcomes have led galvanized researchers to developing objective point of care based imaging tools for assessing OA progression and treatment response. This thesis aims to describe the development and validation of a semi-submerged mechanical three-dimensional ultrasound device against magnetic resonance imaging. The validation of the 3D US device was conducted on a series of imaging phantoms, as well as ten CMC1 OA patients. Two-raters manually segmented areas of synovial …

Expansion Of Myeloid-Derived Suppressor Cells Contributes To Metabolic Osteoarthritis Through Subchondral Bone Remodeling, Lixia Zhang, Cameron L. Kirkwood, Jiho Sohn, Ashley Lau, Mary Bayers-Thering, Supinder Kour Bali, Sridhar Rachala, John M. Marzo, Mark J. Anders, Frank Beier, Keith L. Kirkwood

Bone and Joint Institute

Background: Osteoarthritis (OA) subsequent to acute joint injury accounts for a significant proportion of all arthropathies. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid progenitor cells classically known for potent immune-suppressive activity; however, MDSCs can also differentiate into osteoclasts. In addition, this population is known to be expanded during metabolic disease. The objective of this study was to determine the role of MDSCs in the context of OA pathophysiology. Methods: In this study, we examined the differentiation and functional capacity of MDSCs to become osteoclasts in vitro and in vivo using mouse models of OA and in MDSC …

Diet-Induced Obesity Leads To Behavioral Indicators Of Pain Preceding Structural Joint Damage In Wild-Type Mice, Geoffrey J. Kerr, Bethia To, Ian White, Magali Millecamps, Frank Beier, Matthew W. Grol, Laura S. Stone, Cheryle A. Séguin

Bone and Joint Institute

Introduction: Obesity is one of the largest modifiable risk factors for the development of musculoskeletal diseases, including intervertebral disc (IVD) degeneration and back pain. Despite the clinical association, no studies have directly assessed whether diet-induced obesity accelerates IVD degeneration, back pain, or investigated the biological mediators underlying this association. In this study, we examine the effects of chronic consumption of a high-fat or high-fat/high-sugar (western) diet on the IVD, knee joint, and pain-associated outcomes. Methods: Male C57BL/6N mice were randomized into one of three diet groups (chow control; high-fat; high-fat, high-sugar western diet) at 10 weeks of age and remained …

The Role Of Pannexin 3 In Forced Exercise Bone Remodelling And Its Potential Implications For Osteoarthritis, Justin Tang

Undergraduate Student Research Internships Conference

Exercise such as running has been hypothesized to be a factor of osteoarthritis development. However, the relationship is unclear as differences in genetic backgrounds may influence the risk of osteoarthritis (OA). The gene Panx3 codes for the Pannexin 3 protein (PANX3), a mechanically sensitive channel that allows for the passage of various signalling molecules in both chondrocytes and osteoblasts (Boassa et al., 2007; Penuela et al., 2013; Zhang et al., 2021). We have previously shown PANX3 to be protective in traumatic osteoarthritis, however beneficial in age-induced osteoarthritis (Moon et al., 2021), suggesting that PANX3’s role in osteoarthritis development …

The Cost-Effectiveness Of A Midvastus Versus Standard Medial Parapatellar Surgical Approach For Total Knee Arthroplasty, Ishita Joshi

Electronic Thesis and Dissertation Repository

The minimally invasive midvastus (MMV) surgical approach for total knee arthroplasty (TKA) is a less invasive technique that has been proposed to accelerate recovery over standard TKA, however, advantages are not yet definitively established. We investigated the cost-effectiveness of MMV TKA versus the standard medial parapatellar (MPP) approach for TKA alongside a randomized controlled trial in patients with knee osteoarthritis. Patients reported resource use as well as indirect costs, and health outcomes were measured using the EQ-5D-5L and the Western Ontario and McMaster Universities Osteoarthritis Index over the 12-month study period. The results of our net benefit regression analysis suggest …

Three-Dimensional Ultrasound Imaging For Quantifying Knee Cartilage Volume, Samuel Papernick

Electronic Thesis and Dissertation Repository

Arthritis is the most common chronic health condition in Canada, with the most common form being osteoarthritis (OA). There is a great clinical need for an objective imaging-based point-of-care tool to assess OA status, progression, and response to treatment. This thesis aims to validate a handheld mechanical three-dimensional (3D) ultrasound (US) device against the current clinical standard of magnetic resonance imaging (MRI) for quantifying femoral articular cartilage (FAC) volume. Knee images of 25 healthy volunteers were acquired using 3D US and 3.0 Tesla MRI scans. Two raters manually segmented the trochlear FAC during separate sessions to assess intra- and inter-rater …

Reducing Length Of Stay After Total Hip And Knee Arthroplasty: Assessing Cost-Effectiveness, Caregiver Involvement And Surgical Approach, Bryn O. Zomar

Electronic Thesis and Dissertation Repository

Purpose

The overall purpose of this dissertation was to evaluate factors related to reducing length of stay after total hip and knee arthroplasty (THA and TKA).

Methods

Study 1 was a randomized controlled trial (RCT) to investigate the cost-effectiveness of outpatient THA compared to standard overnight stay. Study 2 was a prospective cohort study to assess patient- and caregiver-related factors and how they may relate to caregiver strain and level of assistance when caring for patients undergoing THA and TKA. Finally, Study 3 was a 2x2 factorial RCT to compare the trajectory of early functional recovery between the medial parapatellar …

Joint Protection Programs For People With Hand Arthritis, Pavlos Bobos

Electronic Thesis and Dissertation Repository

The fact that Joint Protection Programs (JPP) can reduce pain and improve function is based on small, but definitive Randomized Controlled Trials (RCTs), conducted in the 1980s. However, changes over time in the nature of hand use, the rapid expansion of technology, and improvements in our understanding of health literacy mean that these programs are now outdated. Further, problems with adherence to JPP are well documented. The purpose of this thesis was 1) to conduct a scoping review to map all the available evidence around joint protection programs in published and unpublished studies 2) to evaluate the effectiveness of joint …

Evaluation Of The Content Validity Index Of The Australian/Canadian Osteoarthritis Hand Index, The Patient-Rated Wrist/Hand Evaluation And The Thumb Disability Exam In People With Hand Arthritis, Pavlos Bobos, Joy C. Macdermid, Eleni C. Boutsikari, Emily A. Lalone, Louis Ferreira, Ruby Grewal

Bone and Joint Institute

© 2020 The Author(s). Background: The Australian/Canadian Osteoarthritis Hand Index (AUSCAN), the Patient-Rated Wrist/Hand Evaluation (PRWHE) and the Thumb Disability Exam (TDX) are patient-reported outcome measures (PROM) designed to assess pain and hand function in patients with hand arthritis, hand pain and disability, or thumb pathology respectively. This study evaluated the content validity of AUSCAN, PRWHE and TDX in people with hand arthritis. Methods: This study enrolled participants with hand arthritis to rate the items of all 3 PROM in terms of relevance and clarity. The Content Validity Index (CVI) was computed for each item in each scale (I-CVI) as …

Quantitative Magnetic Resonance Imaging Of Knee Articular Cartilage And Effusion-Synovitis: The Structural Response To Changes In Joint Loading, Hayden F. Atkinson

Electronic Thesis and Dissertation Repository

Knee osteoarthritis (OA) is a progressive degenerative condition that can affect all tissues within the joint. Methods to measure early changes in joint structures and the effect of interventions are required. The purpose of this thesis was to investigate aspects of quantitative magnetic resonance imaging (MRI) as outcome measures in knee OA studies. Specifically, changes in articular cartilage composition and/or effusion-synovitis were examined in people with or at risk for knee OA and healthy controls, and after altering joint loads.

Chapter 2 is a systematic review that studied articular cartilage composition using MRI T2 and T1ρ relaxation in patients at …

Clinical Outcomes After Anterior Cruciate Ligament Injury: Panther Symposium Acl Injury Clinical Outcomes Consensus Group, Eleonor Svantesson, Eric Hamrin Senorski, Kate E. Webster, Jón Karlsson, Theresa Diermeier, Benjamin B. Rothrauff, Sean J. Meredith, Thomas Rauer, James J. Irrgang, Kurt P. Spindler, C. Benjamin Ma, Volker Musahl, The Panther Symposium Acl Injury Clinical Outcomes Consensus Group, Freddie H. Fu, Olufemi R. Ayeni, Francesco Della Villa, Stefano Della Villa, Scott Dye, Mario Ferretti, Alan Getgood, Timo Järvelä, Christopher C. Kaeding, Ryosuke Kuroda, Bryson Lesniak, Robert G. Marx, Gregory B. Maletis, Leo Pinczewski, Anil Ranawat, Bruce Reider, Romain Seil, Carola Van Eck, Brian R. Wolf, Patrick Yung

Bone and Joint Institute

© The Author(s) 2020. A stringent outcome assessment is a key aspect of establishing evidence-based clinical guidelines for anterior cruciate ligament (ACL) injury treatment. To establish a standardized assessment of clinical outcome after ACL treatment, a consensus meeting including a multidisciplinary group of ACL experts was held at the ACL Consensus Meeting Panther Symposium, Pittsburgh, Pennsylvania, USA, in June 2019. The aim was to establish a consensus on what data should be reported when conducting an ACL outcome study, what specific outcome measurements should be used, and at what follow-up time those outcomes should be assessed. The group reached consensus …

Overexpression Of Mig-6 In The Cartilage Induces An Osteoarthritis-Like Phenotype In Mice, Melina Bellini, Michael A. Pest, Manuela Miranda-Rodrigues, Ling Qin, Jae Wook Jeong, Frank Beier

Physiology and Pharmacology Publications

© 2020 The Author(s). Background: Osteoarthritis (OA) is the most common form of arthritis and characterized by degeneration of the articular cartilage. Mitogen-inducible gene 6 (Mig-6) has been identified as a negative regulator of the epidermal growth factor receptor (EGFR). Cartilage-specific Mig-6 knockout (KO) mice display increased EGFR signaling, an anabolic buildup of the articular cartilage, and formation of chondro-osseous nodules. Since our understanding of the EGFR/Mig-6 network in the cartilage remains incomplete, we characterized mice with cartilage-specific overexpression of Mig-6 in this study. Methods: Utilizing knee joints from cartilage-specific Mig-6-overexpressing (Mig-6 over/over ) mice (at multiple time points), we …

Prevalence And Risk Factors Of Falls In Adults 1 Year After Total Hip Arthroplasty For Osteoarthritis: A Cross-Sectional Study, Susan W. Hunter, Pavlos Bobos, Lyndsay Somerville, James Howard, Edward M Vasarhelyi, Brent Lanting

Physical Therapy Publications

Total hip arthroplasty is very successful in alleviating the pain from osteoarthritis. However, deficits in lower limb strength, gait, and balance after surgery has identified this group at risk of falls. Considering the high number of people annually receiving a total hip arthroplasty, further elaboration of factors associated with falls is needed to refine fall prevention guidelines. The objective was to examine the prevalence and circumstances of falling and the risk factors associated with falling in older adults in the first year after total hip arthroplasty surgery. This was a cross-sectional study involving 108 individuals (age of 72.4 ± 6.5 …

Gsk3787-Loaded Poly(Ester Amide) Particles For Intra-Articular Drug Delivery, Ian J. Villamagna, Danielle M. Mcrae, Aneta Borecki, Xueli Mei, François Lagugné-Labarthet, Frank Beier, Elizabeth R. Gillies

Bone and Joint Institute

© 2020 by the authors. Osteoarthritis (OA) is a debilitating joint disorder affecting more than 240 million people. There is no disease modifying therapeutic, and drugs that are used to alleviate OA symptoms result in side effects. Recent research indicates that inhibition of peroxisome proliferator-activated receptor ffi (PPARffi) in cartilage may attenuate the development or progression of OA. PPARffi antagonists such as GSK3787 exist, but would benefit from delivery to joints to avoid side effects. Described here is the loading of GSK3787 into poly(ester amide) (PEA) particles. The particles contained 8 wt. % drug and had mean diameters of about …

Gsk3787-Loaded Poly(Ester Amide) Particles For Intra-Articular Drug Delivery, Ian J. Villamagna, Danielle M. Mcrae, Aneta Borecki, Xueli Mei, François Lagugné-Labarthet, Frank Beier, Elizabeth Gillies

Physiology and Pharmacology Publications

© 2020 by the authors. Osteoarthritis (OA) is a debilitating joint disorder affecting more than 240 million people. There is no disease modifying therapeutic, and drugs that are used to alleviate OA symptoms result in side effects. Recent research indicates that inhibition of peroxisome proliferator-activated receptor ffi (PPARffi) in cartilage may attenuate the development or progression of OA. PPARffi antagonists such as GSK3787 exist, but would benefit from delivery to joints to avoid side effects. Described here is the loading of GSK3787 into poly(ester amide) (PEA) particles. The particles contained 8 wt. % drug and had mean diameters of about …

Exposure To The Rxr Agonist Sr11237 In Early Life Causes Disturbed Skeletal Morphogenesis In A Rat Model, Holly Dupuis, Michael Andrew Pest, Ermina Hadzic, Thin Xuan Vo, Daniel B. Hardy, Frank Beier

Physiology and Pharmacology Publications

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Longitudinal bone growth occurs through endochondral ossification (EO), controlled by various signaling molecules. Retinoid X Receptor (RXR) is a nuclear receptor with important roles in cell death, development, and metabolism. However, little is known about its role in EO. In this study, the agonist SR11237 was used to evaluate RXR activation in EO. Rats given SR11237 from post-natal day 5 to post-natal day 15 were harvested for micro-computed tomography (microCT) scanning and histology. In parallel, newborn CD1 mouse tibiae were cultured with increasing concentrations of SR11237 for histological and whole-mount evaluation. …

Arthroscopy Association Of Canada Position Statement On Intra-Articular Injections For Knee Osteoarthritis, Michaela Kopka, Brendan Sheehan, Ryan Degen, Ivan Wong, Laurie Hiemstra, Olufemi Ayeni, Alan Getgood, Cole Beavis, Monika Volesky, Ross Outerbridge, Bogdan Matache

Bone and Joint Institute

No abstract provided.

Evaluation Of The Construct Validity Of The Questionnaire To Identify Knee Symptoms Among Individuals Across Canada With Chronic Knee Pain, James Young

Electronic Thesis and Dissertation Repository

The primary purpose of this study was to evaluate the construct validity of the Questionnaire to Identify Knee Symptoms (QuIKS) measurement scale among individuals with chronic knee symptoms consistent with osteoarthritis. Construct validity was assessed using tests of convergent and discriminative validity on 15 pre-specified hypotheses. The secondary objective was to determine the internal consistency reliability of the QuIKS. One hundred and five individuals recruited in select physiotherapy clinics from across Canada were mailed the QuIKS and five other health questionnaires. Fifty-five individuals completed the questionnaire package. While none of the pre-specified construct validity hypotheses were met, nine of the …

Quantitative Analysis Of Three-Dimensional Cone-Beam Computed Tomography Using Image Quality Phantoms, Rudy Baronette

Electronic Thesis and Dissertation Repository

In the clinical setting, weight-bearing static 2D radiographic imaging and supine 3D radiographic imaging modalities are used to evaluate radiographic changes such as, joint space narrowing, subchondral sclerosis, and osteophyte formation. These respective imaging modalities cannot distinguish between tissues with similar densities (2D imaging), and do not accurately represent functional joint loading (supine 3D imaging). Recent advances in cone-beam CT (CBCT) have allowed for scanner designs that can obtain weight-bearing 3D volumetric scans. The purpose of this thesis was to analyze, design, and implement advanced imaging techniques to quantify image quality parameters of reconstructed image volumes generated by a commercially-available …

Wearable Sensors And Total Knee Arthroplasty: Assessing Quantitative Function To Improve The Patient Experience, Megan Fennema

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) is a chronic degenerative disease for which the only long-term solution is total knee arthroplasty (TKA), though many patients are not satisfied with their TKA. Satisfaction in TKA patients is not well understood. Subjective questionnaires and objective functional tests have been previously used to assess TKA outcomes, but both have disadvantages. Wearable sensors have facilitated affordable biomechanical measurement in OA and TKA populations. The objective of this work was to use wearable sensors alongside functional tests with TKA patients to identify quantitative function that related to subjective function and satisfaction. A wearable sensor-setup was validated before implementation in …

Wait Times, Resource Use And Patient-Reported Outcomes For Patients Referred For Total Knee Replacement Surgery, Kate Lebedeva

Electronic Thesis and Dissertation Repository

This prospective cohort study evaluated the usual care pathway for patients referred to total knee arthroplasty (TKA). We measured healthcare resource use, costs and health-related quality of life (HRQoL) over the continuum of care. We also determined the proportion of inappropriate referrals and estimated wait times for initial surgical consultation and TKA. We found that two in five patients referred to specialty care were deemed inappropriate surgical candidates. Prior to referral, few conservative treatment options were tried, and many imaging tests ordered by referring providers were unjustified. Overall, the greatest proportion of costs were borne by the patient or private …

Assessing The Risk Of Falling In Adults One-Year After Total Hip Arthroplasty, William Janes

Electronic Thesis and Dissertation Repository

The purpose of this study was to examine falls prevalence, falls risk factors and knowledge of falls in individuals who have undergone a total hip arthroplasty. There were 135 patients examined at their one-year follow-up appointment for total hip arthroplasty. Our primary outcome, falls prevalence and falls circumstances, found a falls prevalence of 21.5% with identical circumstances to that of average community-dwelling older adults. Female sex, number of prescription medications and multiple joint replacements were found to be significantly associated with the occurrence of falls in the previous year. The Falls Risk for Older People in a Community Setting Questionnaire …

Osteoarthritis, Cerebrovascular Dysfunction And The Common Denominator Of Inflammation: A Narrative Review, B. K. Al-Khazraji, C. T. Appleton, F. Beier, T. B. Birmingham, J. K. Shoemaker

Physiology and Pharmacology Publications

© 2018 The Author(s) Objective: Population-based cohort studies suggest an association between osteoarthritis (OA) and cerebrovascular disease, yet the mechanisms underlying vascular comorbidities in OA remain unclear. The purpose of this narrative review is to discuss the literature examining inflammation in OA with a focus on physiological mechanisms, and whether overlapping mechanisms exist in cerebrovascular dysfunction. Method: A literature search was conducted in PubMed using combinations of search terms: osteoarthritis, cerebrovascular (disease/dysfunction/risk), cardiovascular (disease/dysfunction/risk), aging/ageing, inflammation, inflammatory mediators, cytokine, c-reactive protein, interleukin, advanced glycation end-products, metabolic syndrome, reactive oxidative species, cognitive impairment, (vascular-related) dementia, small cerebral vessel disease, endothelial function, …

Analysis Of Subchondral Bone And Microvessels Using A Novel Vascular Perfusion Contrast Agent And Optimized Dual-Energy Computed Tomography, Justin J. Tse

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA), is a chronic debilitating disease that affects millions of individuals and is characterized by the degeneration of joint subchondral bone and cartilage. These tissue degenerations manifest as joint pain, limited range of joint motion, and overall diminished quality of life. Currently, the exact mechanism(s) and cause(s) by which OA initiates and progresses remain unknown. The multi-factorial complex nature of OA (i.e. age, diabetes, obesity, and prior injuries have all been shown to play a role in OA) contributes to the current lack of a cure or effective long-term treatment for OA.

One re-emerging and interesting hypothesis …

Position Statement Of The Arthroscopy Association Of Canada (Aac) Concerning Arthroscopy Of The Knee Joint—September 2017, Ivan Wong, Laurie Hiemstra, Olufemi R. Ayeni, Alan Getgood, Cole Beavis, Monika Volesky, Ross Outerbridge, Brendan Sheehan, Robert Mccormack, Robert Litchfield, Daniel Whelan, Nicholas Mohtadi, Catherine Coady, Peter B. Macdonald

Bone and Joint Institute

No abstract provided.

Liver X Receptor And Retinoid X Receptor In Cartilage Development And Homeostasis, Man-Ger Sun

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) is a heterogeneous and multifactorial degenerative disease characterized by cartilage degradation in the joint. Available treatment options target symptoms but do not address the underlying issue of joint tissue degeneration. A better understanding of the molecular mechanisms maintaining cartilage health is essential for developing novel therapeutic strategies. Previous studies have shown the nuclear receptor Liver X Receptor (LXR) to possess protective roles against cartilage breakdown in OA, however the underlying mechanisms behind this process remain unknown. Since LXR regulates transcription by forming obligate heterodimers with another nuclear receptor, the Retinoid X Receptor (RXR), I hypothesized that LXR and …

Pannexins 1 And 3 In Skeletal Health And Osteoarthritis, Paxton M. Moon

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) is a disease that gradually robs affected individuals of their mobility and places a substantial burden on health care systems and economies. OA results from pathological changes in bone, cartilage, synovium and supporting structures which are all essential to joint function. Cartilage degeneration, a hallmarking feature of OA, is an irreversible and untreatable consequence of these changes. Though the mechanisms underlying the initiation of cartilage breakdown remain unclear, joint injury and aging are risk factors. Pannexins (PANXs), a novel family of channel forming glycoproteins, have been suggested as important mediators of early OA. Therefore, my thesis tested the …