Osteoarthritis

The YDAN master protocol will support two independent studies, J3R-MC-YOA1 and J3R-MC-YOA2. Each study will investigate how well and safely Eloralintide (LY3841136) works in adults with obesity or overweight who have osteoarthritis (OA) of the knee with pain. Participation in the study will last about 75 weeks, including screening.

The GZPT master protocol will support two independent studies, J2A-MC-GZT1 and J2A-MC-GZT2. Each study will see how well and safely orforglipron works in people with obesity or overweight who have osteoarthritis (OA) of the knee with pain. Participation in the study will last about 74 weeks.

Brucellosis is a globally distributed zoonosis with persistent clinical management challenges. The World Health Organization(WHO)-recommended doxycycline-rifampin (DOX-RIF) dual regimen may drive rifampin-associated antimicrobial resistance across all brucellosis-endemic regions. Patients with osteoarticular brucellosis require long-term intravenous ceftriaxone triple therapy, which is linked to poor treatment adherence due to repeated hospital visits and outpatient care demands. Fluoroquinolones (levofloxacin \[LVX\], moxifloxacin \[MXF\]) exert excellent anti-Brucella activity and superior bone-joint penetration, yet high-quality multicenter prospective data comparing rifampin-sparing LVX-DOX/MXF-DOX dual regimens against standard RIF-DOX remain rarely reported. Existing comparative studies are limited to small single-center retrospective cohorts or trials pairing rifampin with fluoroquinolones rather than rifampin-free dual oral therapy. This multicenter prospective parallel-cohort protocol includes Module I (non-inferiority design) : 200 patients with uncomplicated acute brucellosis receiving 6-week dual oral therapy; and Module II (non-inferiority design) : 150 patients with imaging-confirmed osteoarticular brucellosis receiving 12-week triple therapy. Clinical data of standardized clinical, laboratory, radiologic, and subsequent longitudinal follow-up data will be collected via centralized electronic data capture. Primary endpoints include clinical and microbiological cure rates at 6 weeks (Module I) and 12 weeks (Module II). Secondary endpoints measure 24-week post treatment recurrence, 24- and 48-week radiologic improvement for osteoarticular disease, and adverse events during treatment. Multivariate regression and Cox models will identify independent prognostic factors and construct a generalizable recurrence risk prediction model. This clinical trial fills a critical evidence gap for oral fluoroquinolone-based regimens, with findings intended to supply supplementary brucellosis treatment approach, reduce rifampin resistance pressure, and eliminate reliance on prolonged parenteral therapy for complicated brucellosis.

The purpose of this clinical trial is to compare the analgesic effects (relief of pain) of glucocorticoids (steroids) and pain medication versus pain medication alone in adult patients presenting to the emergency department with joint pain due to osteoarthritis. Steroids are drugs that can reduce inflammation and are used commonly for many different medical conditions. In brief, the central aims of the study are to: 1. Assess the efficacy of adding oral glucocorticoid medications to the standard pain medications used to treat the pain of osteoarthritis. 2. Assess the safety and tolerability of oral glucocorticoid medication for the short-term treatment of osteoarthritis pain. We hypothesize that: 1) The addition of glucocorticoids to standard pain medications will improve reported pain scores at 3 days following the initiation of treatment compared to standard pain medications alone and 2) The use of glucocorticoids will be well tolerated. Participants in the study will be randomized (like flipping a coin) into one of three groups: 1. Study Group 1 (Control) receiving placebo pills (no active ingredient) once a day for 5 days, plus ibuprofen (pain medication) for 5 days. 2. Study Group 2 (Intervention A) who will receive prednisone (steroid) once a day for 5 days, plus ibuprofen (pain medication) for 5 days. 3. Study Group 3 (Intervention B) who will receive one dose of dexamethasone (steroid) followed by placebo pills (no active ingredient) once a day for 4 days, plus ibuprofen (pain medication) for 5 days. In all groups, acetaminophen (a different pain medication) can be taken as needed for pain that is not controlled with ibuprofen. Participants will: * Receive follow up phone calls at 1, 3, 7 and 14 days. * Report pain scores related to joint pain. * Report the number of pills taken of the various medications used in the study. * Report any adverse events incurred during the follow up period.

Diseases of bone associated with ageing, including osteoporosis (OP) and osteoarthritis (OA), reduce bone mass, bone strength and joint integrity. Current non-surgical approaches are limited to pharmaceutical agents that are not disease modifying and have poor patient tolerability due to side effect profiles. Developing a fundamental understanding of cellular bone homeostasis, including how key cell types affect tissue health, and offering novel therapeutic targets for prevention of bone disease is therefore essential. This is the focus of OSTEOMICS. A number of factors have been linked to increased risk of bone disease, including genetic predisposition, diet, smoking, ageing, autoimmune disorders and endocrine disorders. In our study, we will recruit patients undergoing elective and non-elective orthopaedic surgery and obtain surgical bone waste for analysis. This will capture a cohort of patients with bone disorders like OP and OA, in addition to patients without overt clinical bone disease. We will study the relationship between the molecular biology of bone cells, bone structure, genetics (DNA) and environmental factors with the aim of identifying and validating novel therapeutic targets. We will leverage modern single cell technologies to understand the diversity of cell types found in bone. These technologies have now led to the characterisation of virtually every tissue in the body, however bone and bone-adjacent tissues are massively underrepresented due to the anatomical location and underlying technical challenges. Early protocols to demineralise bone and perform single cell profiling have now been developed. We will systematically scale up these efforts to observe how genetic variation at the population level leads to alterations in bone structure and quality. Over the next 10 years, we will generate data to comprehensively characterise bone across health and disease, use machine learning to drive analysis, and experimentally validate hypotheses - which will ultimately contribute to developing the next generation of therapeutic agents.

The goal of this RCT is to compare efficacy between mirogabalin and pregabalin in pain reducing after unilateral primary total knee arthroplasty. The main question\[s\] it aims to answer are: • Does mirogabalin have better pain reduction than pregabalin after unilateral primary total knee arthroplasty. Participants will randomized to mirogabalin or pregabalin group and will take the drug for 2 weeks after TKA. Researchers will compare to pregabalin group to see pain and functional outcomes after TKA.

To evaluate serum and synovial fluid 15-PGDH levels in patients with osteoarthritis and ankylosing spondylitis and determine their associations with clinical and musculoskeletal ultrasound features. To compare 15-PGDH concentrations among patients with knee osteoarthritis, and ankylosing spondylitis with knee effusion To evaluate whether serum 15-PGDH reflects intra-articular 15-PGDH concentrations. Analysis the level of 15-PGDH in relation to disease activity and severity of both diseases.

Brief Summary: This single-blind, randomized controlled trial will investigate the efficacy of bee venom phonophoresis in managing pain and improving mobility in patients with knee osteoarthritis. Thirty adults aged 40-75 years with clinically and radiographically confirmed knee osteoarthritis will be randomly assigned to receive either bee venom phonophoresis or placebo phonophoresis with a neutral gel. Ultrasound parameters will be standardized for all participants. Primary outcomes are pain reduction, measured by the Visual Analog Scale (VAS), and functional mobility, assessed by the Timed Up and Go (TUG) test. The secondary outcome is walking endurance, measured by the Six-Minute Walk Test (6MWT). Assessments will be conducted at baseline and post-intervention. The study is designed to determine whether bee venom phonophoresis offers greater clinical benefit compared to placebo phonophoresis, potentially providing a non-invasive, adjunctive treatment option for knee osteoarthritis. Ethical approval has been obtained from the Faculty of Physical Therapy, Sinai University, and all participants will provide written informed consent.

The goal of this study is to demonstrate the safety and performance of the Incompass™ Total Ankle System after surgery over the standard follow-up period. The study will measure improvements in patient-reported information related to quality of life and pain following surgery. In order to do this, medical imaging (i.e. X-Rays, CT scans) which have been taken as part of routine care, will be reviewed. Any additional X-Rays conducted during the period of the research will also be reviewed. The Incompass™ Total Ankle System has been cleared by the Food and Drug Administration (FDA). The products are already in use routinely in ankle replacement surgeries. No part of this study is experimental.

Patients will be asked to take part in this research study because they have mild-to-moderate knee osteoarthritis (OA) and were referred clinically for a procedure called Genicular Artery Embolization (GAE). Osteoarthritis is the most common form of arthritis. It occurs when the protective cartilage that cushions the ends of the bones wears down over time. The symptoms of OA include pain or aching, stiffness, decreased range of motion, and swelling. The purpose of this study is to evaluate the safety and effectiveness of GAE for the treatment of knee pain attributed to OA. Research participants will be in this research study for about 3 years. The study includes a screening visit, GAE procedure, and six follow-up visits. At the screening visit, a review of their medical history, demographics, and medications will be collected; physical examination will be completed; knee x-ray will be done; and two questionnaires on your knee pain will be administered. The GAE procedure will involve receiving sedation or medication to help them relax, lidocaine injected under the skin in the area of the body where catheters will be inserted into one of your arteries and then using x-ray, a catheter will be directed to the arteries supplying the lining of the knee. Then tiny microspheres will be injected into the artery to decrease the blood supply to this knee joint tissue. The follow-up visits up to 12 months will include a focused physical examination of the treated knee, documentation of medications, and two questionnaires will be administered. The follow-up visits at year 2 and 3 will include documentation of medications and any new treatments for OA as well as completion of two questionnaires. Follow-up visits maybe conducted in clinic or remotely.

This randomized controlled trial aims to compare the effectiveness Weighted dangling exercises versus vastus medialis oblique muscle neuromuscular electrical stimulation(VMO+NMES) in patients with knee osteoarthritis. The study will recruit 48 participants (accounting for 10% attrition), aged 40-60 years, from University of Lahore Teaching Hospital using convenience sampling. Participants will be randomly allocated into two groups: an interventional group receiving WDE and other interventional group undergoing VMO strength training with NMES. Both interventions will be administered three times per week for 8 weeks under professional supervision. Outcome measures including pain intensity (NPRS), Functional Disability (Western Ontario and McMaster Universities Osteoarthritis Index),Muscle Strength (MMT) will be assessed at baseline, 4 weeks, and 8 weeks. Data will be analyzed using SPSS, with appropriate parametric or non-parametric tests applied after checking data normality. Ethical approval will be obtained, informed consent will be secured, and participant confidentiality will be strictly maintained.

The purpose of this research is to gather clinical and radiographic (X-ray) information about EMPHASYS™ acetabular shell (also called a hip 'cup') placement in total hip replacement surgery using a non-invasive surgical navigation system called VELYS™ hip navigation system with CUPTIMIZE™ Advanced Hip-Spine Analysis software. Data collected in this study will be compared with data collected from implantations using different cup positioning instrumentation and techniques to assess performance.

TXA2 inhibits the expression of the primary marker of thermogenesis (UCP1) while prostacyclin (PGI2), another metabolite derived from arachidonic acid, enhances its expression. Given the close relationship between the adipocyte and the chondrocyte, the study team hypothesises that thromboxane A2 controls chondrocyte formation and function and thus cartilage homeostasis. The study objectives are: i) to analyse the role of TXA2 on chondrocyte differentiation in vitro, ii) to determine the association between circulating and tissue TXA2 levels in a rat model of osteoarthritis, and iii) to correlate circulating and synovial fluid levels of TXA2 with the development of osteoarthritis in a small human cohort. The proposed research aims to better understand the mechanisms underlying the role of lipid metabolites in chondrocyte formation and function, paving the way for the development of nutritional and pharmacological therapies to combat OA and associated metabolic disorders.

Osteoarthritis is a common disease whose prevalence continues to increase. To date, there is no medical treatment that has proven effective, and only symptomatic treatments exist, mainly to reduce pain. Arthroplasty, a costly and invasive surgical procedure, is often unavoidable in advanced stages of the disease. More than just a degenerative disease of the cartilage, osteoarthritis is now recognised as a heterogeneous disease causing multi-tissue damage of varying intensity. Synovitis plays a particularly important role in the onset and progression of osteoarthritis and has been closely correlated with radiographic severity, pain and loss of joint function. The investigators have identified several synovial histological pathotypes based on the type of synovial cell infiltrate and its distribution in samples from advanced osteoarthritis (surgical waste from prosthesis implantation). The investiogators' studies show that the presence of these pathotypes appears to be related to the clinical phenotype of patients. Analysis of synovial tissue at earlier stages of the disease is now essential to advance the understanding of the role of synovitis in osteoarthritis and its link to the clinical phenotype of patients. The objective of this protocol is to describe the different synovial histological pathotypes present in the early stages of osteoarthritis; To this end, the investigators will establish a cohort of osteoarthritis patients with a collection of synovial tissue samples obtained by ultrasound-guided needle biopsy in an outpatient setting, a well-tolerated procedure with simple follow-up, as well as blood sampling.

Intra-articular platelet-rich plasma (PRP) injection is a widely used treatment for knee osteoarthritis, but patients respond to it very differently and there is currently no simple, inexpensive way to predict who will benefit. The neutrophil-to-lymphocyte ratio (NLR) and related indices derived from a routine complete blood count reflect a person's baseline inflammatory state. This prospective single-arm observational cohort study investigates whether the baseline NLR, together with the platelet-to-lymphocyte ratio (PLR), the systemic immune-inflammation index (SII), and the monocyte-to-lymphocyte ratio (MLR), predicts the clinical response to intra-articular PRP in patients with Kellgren-Lawrence grade 2 to 3 knee osteoarthritis. The investigators will enroll 120 patients aged 40 to 60 years, each of whom receives a standardized course of three leukocyte-poor PRP injections one week apart. Patients are followed for 6 months, and the primary clinical outcome is the change in the WOMAC osteoarthritis index at 6 months. Outcome assessors are blinded to patients' blood-count values. If a baseline blood ratio predicts response, it could become a low-cost tool to guide patient selection for PRP.

The Endoprosthesis Registry Heidelberg (EPR-HD) is a clinical registry designed to systematically collect and analyze data from patients undergoing primary implantation or revision surgery of artificial hip and knee joints. The main objective of the registry is to evaluate long-term outcomes, complication rates, implant survival, and functional results associated with joint replacement procedures in patients with various hip and knee joint pathologies. By gathering comprehensive clinical data, EPR-HD aims to improve the understanding of patient outcomes after endoprosthetic procedures, identify potential factors influencing implant success, and support evidence-based improvements in surgical techniques and patient care. The registry includes adult patients treated at Heidelberg University Hospital, with data collected at multiple time points during routine clinical follow-up. This registry will contribute to the optimization of joint replacement strategies and promote high-quality patient care.

This prospective randomized controlled trial aims to compare the pharmacokinetic profiles of intraosseous and intravenous tranexamic acid administration in patients undergoing primary total joint arthroplasty. Eligible patients undergoing total hip or total knee arthroplasty will be randomly assigned to receive tranexamic acid either through intraosseous injection or intravenous injection at a dose of 15 mg/kg. Blood samples will be collected at predefined time points to evaluate plasma concentrations and pharmacokinetic characteristics of tranexamic acid. Secondary outcomes include coagulation function, intraoperative blood loss, transfusion rate, and hemoglobin changes. The study aims to provide evidence regarding the pharmacokinetic characteristics and clinical feasibility of intraosseous tranexamic acid administration in joint arthroplasty.

The goal of this observational study is to analyse the cartilage and bone forming potential of cells isolated from the tissues of patients undergoing surgery for the treatment of polydactyly, hip dislocation and from other bio-banked cartilage tissues. The main question it aims to answer is: Which of the following tissues from polydactyly digit, iliac apophysis or other bio-banked cartilage produce better cartilage in vitro and in vivo? Participants receiving digit amputation surgery for treatment of polydactyly will be asked to donate the associated waste tissue whilst participants receiving surgery to treat a dislocated hip will be asked to donate an extra small piece of cartilage tissue (approximately 1 gram) from the iliac apophysis. Other tissues for the study will be obtained from those donated to biobanks.

This study compares the efficacy of a 5-day post-operative oral prednisone regimen (40 mg daily) with the standard intraoperative steroid regimen, focusing on pain, swelling, range of motion, opioid use, and glucose levels monitored continuously.

Chronic musculoskeletal pain (CMP), while a leading cause of physical disablement, is a neglected national health disparity issue in Black communities. The purpose of this study is to test a novel culturally congruent pain self-management intervention. A total of 120 persons aged 50-92, self-identifying as Black or African American having CMP will be invited to participate in this study. The primary outcome measured throughout this 3-year study is movement-evoked pain (MEP).

This study aims to develop and validate an artificial intelligence (AI)-based predictive model to estimate the risk of incident onset of five major diseases or conditions: cardiovascular disease, type 2 diabetes mellitus, breast cancer, low back pain, and osteoarthritis, in adults aged 30 to 60 years. For each participant, an index date will be defined as the date of a prior health screening or another protocol-defined baseline clinical date. Incident disease status for each target disease or condition will be ascertained by retrospective review of electronic medical records for up to 10 years after the index date. The study integrates retrospective clinical, health screening, laboratory, imaging, and electronic medical record data with prospectively collected biospecimen, proteomic, genomic, questionnaire, lifestyle, and digital health data. Prospective study procedures will be completed over approximately 1 week, with up to 2 additional weeks if needed. By combining multimodal data, this study seeks to improve disease risk prediction and to identify clinical and biological factors associated with disease onset, ultimately supporting personalized risk stratification and preventive healthcare strategies.

Title: Personalized Total Knee Arthroplasty: Computer-Assisted Navigation vs. Robotic Assistance (CAN-ARD). Summary: Knee osteoarthritis is frequently treated with Total Knee Arthroplasty (TKA). However, approximately 20% of patients remain dissatisfied following the procedure. This study aims to compare two surgical assistance technologies designed to improve prosthetic placement accuracy: Computer-Assisted Navigation (CAN) and Robotic-Arm Assistance (RA). The primary objective is to determine if there is a significant difference in functional outcomes and the "forgotten joint" sensation (measured by the Forgotten Joint Score - FJS) between patients operated on with robotic assistance versus those with traditional navigation at 3, 12, and 24 months post-surgery. The study's hypothesis is that there is no major clinical difference between these two techniques when applied within a personalized alignment strategy.

The goal of this clinical trial is to evaluate the safety of arterial embolization using Lipiodol® in patients with symptomatic hand osteoarthritis refractory to conventional treatment. It will also learn about the efficacy of arterial embolization with Lipiodol® in reducing pain and improving hand function. The main questions it aims to answer are: * What are the side effects and complications associated with the Lipiodol® arterial embolization procedure? * Does arterial embolization reduce pain intensity and improve hand function? Researchers will evaluate patients over a 6-month period to assess the safety of Lipiodol® embolization and its impact on joint pain, swelling, and functional capacity. Participants will: * Undergo arterial embolization with Lipiodol® * Participate in regular follow-ups to monitor pain relief, hand function, and any side effects * Have imaging studies to assess changes in joint vascularisation and damage

Osteoarthritis and mild cognitive impairment are common conditions that share underlying biological processes related to metabolism and inflammation. This study will examine whether a well-formulated ketogenic diet influences pain, physical function, and cognitive outcomes in adults with osteoarthritis and mild cognitive impairment. Participants will follow a supervised ketogenic dietary intervention, with assessments conducted before and after the intervention to evaluate changes in symptoms and related biological markers. The goal of this study is to better understand shared mechanisms between joint pain and cognitive health and to explore whether a ketogenic dietary approach may support symptom management in these populations.

The goal of this clinical trial is to learn if the VELYS Robotic-Assisted Solution (VRAS) device helps to improve outcomes from total knee replacement, when compared to regular non-robotic-assisted total knee replacement in the treatment of osteoarthritis. It will also aim to review the longer-term safety and efficiency effects of using this device. The main questions it aims to answer are: 1. Does VRAS device-assisted total knee replacement improve patient outcomes (such as their function, satisfaction, and pain) when compared to non-robotic-assisted total knee replacement? 2. Does VRAS device-assisted total knee replacement improve clinical outcomes (such as revision risk, complications, and hospital length of stay) when compared to non-robotic-assisted total knee replacement? 3. Does VRAS device-assisted total knee replacement improve functional outcomes (including biomechanical motion analysis) when compared to non-robotic-assisted total knee replacement? 4. What are the economic and efficiency effects of VRAS device-assisted total knee replacement compared to non-robotic-assisted total knee replacement? 5. What are the human factor and learning curve effects of introducing VRAS device-assisted total knee replacement into healthcare teams? 6. Are there any differences in safety and adverse event incidence between VRAS device-assisted total knee replacement and non-robotic-assisted total knee replacement? Participants will: * Be randomised to receive a total knee replacement using either regular non-robotic-assisted methods, or with the use of the VRAS device. * Be assessed pre-operatively at the clinic, and then at 6 weeks, 6 months, and 12 months following date of operation. At these appointments patients will answer questionnaires, receive an x-ray (pre-operatively, and at 6 months post-operatively), and a subgroup will be reviewed in the motion analysis laboratory (pre-operatively, and at 6 months post-operatively). * Have their longer-term outcomes including any revision operations monitored out to 10 years through national registry data linkage (no actual follow-up for patients after 12 months).