Single Injection AAV2-FGF18 Gene Therapy Reduces Cartilage Loss and Subchondral Bone Damage in a Mechanically Induced Model of Osteoarthritis.

Background: Osteoarthritis (OA) is a highly debilitating, degenerative pathology of cartilaginous joints affecting over 500 million people worldwide. The global economic burden of OA is estimated at $260-519 billion and growing, driven by aging global population and increasing rates of obesity. To date, only the multi-injection chondroanabolic treatment regimen of Fibroblast Growth Factor 18 (FGF18) has demonstrated clinically meaningful disease-modifying efficacy in placebo-controlled human trials.

Gender and age differences in the associations between cortical thickness and hand osteoarthritis severity: data from the Osteoarthritis Initiative.

Objective: To evaluate gender differences in the association between metacarpal cortical thickness (T)-a surrogate for bone density-and severity of radiographic hand osteoarthritis (HOA) in a longitudinal observational study.

Method: Hand radiographs of 3575 participants (2039 F/1536 M) from the Osteoarthritis Initiative were assessed at baseline and 48 months. A reader used a semi-automated software tool to calculate T, a measurement of the cortical thickness, for metacarpals 2-4.

Radiomic features of the medial meniscus predicts incident destabilizing meniscal tears: Data from the osteoarthritis initiative.

The objective of this study was to determine the optimal meniscal radiomic features to classify people who will develop an incident destabilizing medial meniscal tear. We used magnetic resonance (MR) images from an existing case-control study that includes images from the first 4 years of the Osteoarthritis Initiative (OAI). For this exploratory analysis (n = 215), we limited our study sample to people with (1) intact menisci at the OAI baseline visit, (2) 4-year meniscal status data, and (3) complete meniscal data from each region of interest.

Bicycling over a Lifetime Is Associated with Less Symptomatic Knee Osteoarthritis: Data from the Osteoarthritis Initiative.

Introduction: This study aimed to evaluate the relationship between a history of bicycling and symptomatic and structural outcomes of knee osteoarthritis (OA), the most common form of arthritis.

Methods: This was a retrospective, cross-sectional study within the Osteoarthritis Initiative (OAI), where we investigated OAI participants with complete data on bicycling, knee pain, and radiographic evidence of knee OA. We used a self-administered questionnaire at the 96-month OAI visit to identify participation in bicycling during four time periods throughout a participant's lifetime (ages 12-18, 19-34, 35-49, and >50 yr).

Gardening/yardwork in people with knee osteoarthritis is not associated with symptom or structural progression over 48 months: data from the Osteoarthritis Initiative.

Objective: To evaluate the relationship of gardening/yardwork with symptomatic and structural progression in those with pre-existing radiographic knee osteoarthritis (OA) in the Osteoarthritis Initiative (OAI), an observational study designed to evaluate potential and known biomarkers and risk factors of knee OA.

Methods: We conducted a cohort study nested within the OAI, including participants ≥ 50 years old with radiographic OA in at least one knee at the time of OAI enrollment. A participant reported the level of gardening/yardwork activity in a self-administered survey.

Predicting the onset of end-stage knee osteoarthritis over two- and five-years using machine learning.

Objective: Identifying participants who will progress to advanced stage in knee osteoarthritis (KOA) trials remains a significant challenge. Current tools, relying on total knee replacements (TKR), fall short in reliability due to the extraneous factors influencing TKR decisions. Acknowledging these limitations, our study identifies a critical need for a more robust metric to assess severe KOA.

Association of Weight Loss and Weight Gain With Structural Defects and Pain in Hand Osteoarthritis: Data From the Osteoarthritis Initiative.

Objective: Our aim was to define the association of weight change (weight loss or weight gain) with the incidence and progression of hand osteoarthritis (OA), assessed either by radiography or by pain, using data from the Osteoarthritis Initiative.

Methods: Among the 4,796 participants, we selected 4,598 participants, excluding those with cancer or rheumatoid arthritis or a body mass index under 18.5 kg/m.

Evaluation of a measure of end-stage knee osteoarthritis compared to total knee replacement: An observational study using multicohort data.

Objectives: To determine if an end-stage knee osteoarthritis (esKOA) measure, based on symptomatic and radiographic criteria, can indicate progression to severe KOA earlier and with fewer research participants than total knee replacement (TKR). We employed both interventional and observational study designs as examples to estimate the required sample sizes. EsKOA in a knee was declared if either of the following two conditions were met: 1) moderate, intense, or severe symptoms of KOA indicated by pain and disability measurement and severe KOA indicated by radiographically-assessed knee structure; 2) intense or severe symptoms of KOA indicated by pain and disability measurement and frequent knee pain with mild or moderate KOA as indicated by radiographically-assessed knee structure.

Knee cartilage change on magnetic resonance imaging: Should we lump or split topographical regions? A 2-year study of data from the osteoarthritis initiative.

Objective: We challenge the paradigm that a simplistic approach evaluating anatomic regions (e.g., medial femur or tibia) is ideal for assessing articular cartilage loss on magnetic resonance (MR) imaging.

Safety, Tolerability, and Pharmacokinetics of Same-Knee Intra-Articular Injection of Corticosteroid and Lorecivivint Within 7 Days: An Open-Label, Randomized, Parallel-Arm Study.

Introduction: Knee osteoarthritis (OA) is a common painful disorder. Intra-articular (IA) corticosteroid injections are frequently prescribed to treat knee pain. Lorecivivint (LOR), a novel IA cdc2-Like Kinase (CLK)/Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase (DYRK) inhibitor thought to modulate Wnt and inflammatory pathways, has appeared safe and demonstrated improved patient-reported outcomes compared with placebo.

Strength Training Is Associated With Less Knee Osteoarthritis: Data From the Osteoarthritis Initiative.

Objective: We aimed to evaluate the relationship of a history of strength training with symptomatic and structural outcomes of knee osteoarthritis (OA).

Methods: This study was a retrospective, cross-sectional study within the Osteoarthritis Initiative (OAI), a multicenter prospective longitudinal observational study. Data were collected at four OAI clinical sites: Memorial Hospital of Rhode Island, the Ohio State University, the University of Pittsburgh, and the University of Maryland/Johns Hopkins.

Radiographic joint space width in individuals with hand osteoarthritis: Are their "healthy" joints really healthy?

Objectives: We aimed to investigate the systemic nature of hand osteoarthritis (OA). We hypothesized that people who suffer from hand OA would display narrower radiographic joint space width (JSW) - not only in joints with apparent radiographic OA but also in their unaffected "healthy" joints.

Method: We examined 3394 participants from the Osteoarthritis Initiative with available dominant hand radiographs at baseline.

The Prognostic Potential of End-Stage Knee Osteoarthritis and Its Components to Predict Knee Replacement: Data From the Osteoarthritis Initiative.

Objective: We aimed to determine how 2 definitions of end-stage knee osteoarthritis (esKOA) and each component (knee symptoms, persistent knee pain, radiographic severity, and presence of limited mobility or instability) related to future knee replacement (KR).

Methods: We performed knee-based analyses of Osteoarthritis Initiative data from baseline to the first 4 annual follow-up visits, and data on KR from baseline until the fifth yearly contact. We calculated a base model using common risk factors for KR in logistic regression models with generalized estimating equations.

Meniscal degeneration is prognostic of destabilzing meniscal tear and accelerated knee osteoarthritis: Data from the Osteoarthritis Initiative.

The objective of this study was to assess the prognostic potential of magnetic resonance (MR)-detected meniscal degeneration in relation to incident destabilizing meniscal tears (radial, complex, root, or macerated) or accelerated knee osteoarthritis (AKOA). We used existing MR data from a case-control study of three groups from the Osteoarthritis Initiative without radiographic KOA at baseline: AKOA, typical KOA, and no KOA. From these groups, we included people without medial and lateral meniscal tear at baseline (n = 226) and 48-month meniscal data (n = 221).

The natural history of end-stage knee osteoarthritis: Data from the osteoarthritis initiative.

Objective: We aimed to describe the natural history leading to end-stage knee osteoarthritis (esKOA), focusing on knee symptoms, radiographic severity, and the presence of limited mobility or instability.

Methods: We performed knee-based analyses of Osteoarthritis Initiative data from 7691 knees (4165 participants). We used a validated definition of esKOA that relied on meeting one of two criteria: (1) severe radiographic knee osteoarthritis (Kellgren-Lawrence [KL] grade=4) with moderate-to-intense pain (Likert WOMAC pain+function>11/88) or (2) KL grade<4 with intense or severe pain (WOMAC pain+function>22) and limited mobility (flexion contracture≥5°) or instability (based on a varus and valgus stress test).

FDA/Arthritis Foundation osteoarthritis drug development workshop recap: Assessment of long-term benefit.

Objective: To summarize proceedings of a workshop convened to discuss the current state of science in the disease of osteoarthritis (OA), identify the knowledge gaps, and examine the developmental and regulatory challenges in bringing these products to market.

Design: Summary of the one-day workshop held virtually on June 22nd, 2021.

Results: Speakers selected by the Planning Committee presented data on the current approach to assessment of OA therapies, biomarkers in OA drug development, and the assessment of disease progression and long-term benefit.

Association Between Walking for Exercise and Symptomatic and Structural Progression in Individuals With Knee Osteoarthritis: Data From the Osteoarthritis Initiative Cohort.

Objective: To assess the relationship between walking for exercise and symptomatic and structural disease progression in individuals with knee osteoarthritis (OA).

Methods: We assessed a nested cohort of participants age 50 years or older within the Osteoarthritis Initiative, a community-based observational study in which subjects were enrolled between 2004 and 2006. We focused on 4 dichotomous outcomes from baseline to the 48-month visit, involving determination of the frequency of knee pain and radiographic severity of knee OA on posteroanterior semiflexed knee radiographs.

Increased risk of incident knee osteoarthritis in those with greater work-related physical activity.

Objective: Occupations involving greater physical activity may increase risk for knee osteoarthritis (OA). Existing studies have not evaluated work-related physical activity before OA onset. Hence, we aimed to evaluate the association between work-related physical activity and knee OA incidence.

A novel approach to studying early knee osteoarthritis illustrates that bilateral medial tibiofemoral osteoarthritis is a heritable phenotype: an offspring study.

To assess the potential of studying offspring of people with and without knee osteoarthritis to understand the risk factors and heritability for knee osteoarthritis. We selected two groups of Osteoarthritis Initiative (OAI) participants from one clinical site: (1) participants with bilateral radiographic medial tibiofemoral osteoarthritis and (2) those without tibiofemoral osteoarthritis. We then invited biological offspring ≥ 18 years old to complete an online survey that inquired about osteoarthritis risk factors and symptoms.

Racket or Bat Sports: No Association With Thumb-Base Osteoarthritis.

Context: Repetitive joint use is a risk factor for osteoarthritis, which is a leading cause of disability. Sports requiring a racket or bat to perform repetitive high-velocity impacts may increase the risk of thumb-base osteoarthritis. However, this hypothesis remains untested.