Evaluation of therapeutics strategies for osteoarthritis using contrast based CT imaging

Abstract

Osteoarthritis (OA) affects nearly 27 million people alone and is the leading cause of chronic disability in the US. Current treatment methods target pain relief for OA via non-steroidal anti-inflammatory drugs (NSAIDs) since there are currently no clinically approved disease modifying osteoarthritis drugs (DMOADs) demonstrating efficacy. Despite multiple pre-clinical DMOAD experiments being conducted, the screening rate for drugs is severely limited by the lack of sensitivity of outcome measures and the time consuming process to achieve them. Our lab has previously developed and validated a technique to evaluate articular cartilage changes with micro-CT. The objective of this thesis was to examine two distinct treatment strategies for OA in a rat joint degeneration model using equilibrium partitioning of an ionic contrast agent based micro-CT (EPIC-µCT). We hypothesized that these novel therapeutics will assist in preventing degradation of cartilage after injury and will be measurable by EPIC-µCT. First, we characterized two of the commonly used rat joint degeneration models - monosodium iodoacetate injection (MIA) and transection of medial meniscus (MMT) in rats using EPIC-µCT. The MMT model was then used to test the effects of a matrix metalloproteinase inhibitor (MMPi) using EPIC-µCT to detect changes in articular cartilage. Finally, micronized dehydrated human amnion/chorion membrane (dHACM) was delivered intra-articularly in the MMT model and evaluated as a disease modifying OA drug.