MOST Study Cores

The MOST study is carried out by investigators from multiple intuitions investigating the causes and consequences of osteoarthritis. The current cycle of MOST is managed by the Administrative Core, which oversees the Clinical Data Collection and Management Core, Imaging Core, and Analysis Core; and the Projects.

The MOST Executive Committee, comprised of the Leads and Co-Leads of each Core, oversees the MOST study and integrates, coordinates, plans and directs its various components so that high quality data are collected, cleaned, and analyzed to address the Projects’ aims, and the Cores provide project investigators the data and results needed to address the scientific questions posed.

Administrative Core

Dr. Tuhina Neogi at Boston University is the director of the Administrative Core, working closely with the Executive Committee to manage MOST and integrate, coordinate, plan and direct its various components so that high quality data is collected, cleaned, and analyzed to address the Projects’ aims, and the Cores provide Project investigators the data and results needed to address the scientific questions posed.

The Administrative Core supports and engages an Observational Safety and Monitoring Board (OSMB) (appointed by NIA) and a Community Advisory Board. The Administrative Core also manages ancillary study activities and a new Pilot Grant Program.

Clinical Data Collection and Management Core

The Clinical Data Collection and Management Core (CDCMC) is led by Dr. Peggy Cawthon at the Data Coordinating Center at University of California, San Francisco; and Clinical Center Co-Leads Dr. James Torner at the University of Iowa and Dr. Cora Lewis at the University of Alabama Birmingham.

The CDCMC is responsible for the harmonization and planning of all data collection elements so that each measure is collected in a standardized, rigorous, and efficient manner, and timed appropriately relative to other measures collected (e.g., some measures must be collected prior to or after others). This Core also works with Project leads to ensure that common data elements (e.g., pain and function assessments) are obtained using protocols that can be utilized by all relevant projects.

Imaging Core

The Imaging Core is led by Dr. Michael Nevitt and Co-Lead Dr. John Lynch at the University of California, San Francisco. This core is responsible for ensuring optimal operations of tools and protocols for imaging acquisition, and for providing quality control feedback on acquired images

Analysis Core

The Analysis Core is led by Dr. Michael LaValley at Boston University. The analysis core ensures definitions for common data elements are harmonized across projects. This core will develop variables and datasets needed to address Project aims.

Current MOST Projects

Impaired Exercise Induced Hypoalgesia

Exercise, physical activity and physical therapy are recommended as first-line therapy for knee OA. Normally, a bout of exercise is expected to acutely reduce pain sensitivity, a phenomenon termed exercise induced hypoalgesia (EIH). Some patients with knee OA, however, indicate their pain does not improve or even worsens with exercise. Whether impaired EIH accounts for why up to 60% of people with knee OA do not experience pain improvement with an exercise intervention or experience lack of benefit from physical therapy is not known. Mechanisms underlying impaired EIH, and how impaired EIH may impact pain, function, strength, and physical activity are not well understood. Additionally, whether impaired EIH contributes to avoidance and adverse beliefs about exercise is not known. This project utilizes new data collected through the CDCMC, and the Analysis Core will perform the analyses.

Synovial Fluid Proteomics

Studies examining blood biomarkers for knee OA have failed to reveal strongly predictive markers and only small cross-sectional studies have been conducted using synovial fluid, the fluid that bathes the sites of pathology in the knee. Further, studies have mostly tested candidate biomarkers, not agnostically considering the universe of proteins that could serve as disease biomarkers and provide insights into disease pathogenesis. This project involves examination of the synovial fluid proteome paired with plasma proteome in a subset of MOST participants, tying protein expression to both knee-specific pain and structure outcomes, and to multisite OA that includes knees and hands. The project relies on the CDCMC to collect the synovial fluid and blood plasma, the Imaging Core to characterize OA outcomes, and the Analysis Core to provide data on outcomes and covariates.

Intraarticular Mineralization

Chondrocalcinosis, the appearance of intraarticular (IA) mineralization on radiography, is common in knee OA. However, its clinical consequences remain controversial, in large part due to insensitivity of radiographs to its presence. Another contributing factor may be that the impact of IA mineralization may differ by type of calcium crystal (calcium pyrophosphate (CPP) vs. basic calcium phosphate (BCP)), but this has not been well-studied due to challenges of differentiating the two crystals. Clinically, CPP and BCP cause various clinical conditions, including episodes of pain; whether either of these crystals contribute to pain fluctuation in OA is not known. Recently, using DECT, new image analysis approaches have successfully differentiated CPP from BCP crystals. We will leverage dual-energy CT (DECT) acquired during MOST3, and implement these novel image analysis algorithms to characterize and quantify crystal deposition. We will evaluate  the relation of IA mineralization and crystal type to pain fluctuation. Additionally, because calcium crystals can cause release of IL-1β and given the interest in targeting an inflammatory phenotype of OA with anti-IL-1 therapy, we will examine the systemic and synovial fluid inflammatory profiles of IA mineralization and separate crystal types using fluid collected in MOST4 by Project 2. This project uses all 3 Cores (CDCMC, Imaging Core, and Analysis Core).