STUDY OBJECTIVES: To determine whether the bony abnormalities observed in a knock-in mouse model for osteogenesis imperfecta (?brittle mice?) leads to degenerative joint changes similar to osteoarthritis. In this study we have utilized an animal model with a known mutation of Type 1 collagen (Osteogenesis Imperfecta, ?brittle? mice), to investigate the early radiographic changes in the articular cartilage and the subchondral bone of the knee joints. A combination of micro-MRI, and micro-CT scans; both non-invasive imaging techniques, are applied to obtain serial, high-resolution images of the cartilage and subchondral bone of the articular surfaces of the knees in the study animals. MRI is thought to be highly sensitive in detecting early cartilage abnormalities. Longitudinal studies show that MRI is able to detect joint abnormalities as early as 6 months before conventional radiographs. However its utility in differentiating true bone erosions from bone marrow edema is unknown. In contrast to the MRI images, CT visualizes bone directly. Our investigation began in May 2004; and we have thus far evaluated four groups of ?brittle? animals between the ages of 2, and 22 months. These have been compared to normal age-matched, control animals. Study Goals: To use contrast enhanced micro-MRI and micro-CT scan to serially examine the knee joints of the brittle mice and age related wild type animals. To characterize these changes in animals at varying stages of bone maturation and degeneration. To validate the nature of the radiographic abnormalities with corresponding, histopathology sections of bone and cartilage tissue taken from the imaged joints. The results of this comparative study will be used to aid in the development of imaging parameters for detecting the earliest connective tissue changes in Collagen Type I and Type II degenerative diseases. The knowledge we gain from conducting this animal experiment may aid us in detecting the site(s) of the earliest triggering events in OA. By focusing on the subchondral bone of aging ?brittle mice? we maybe able to elucidate what role, if any, Type I collagen plays in this degenerative process. euthanized, an approved MR contrast agent will be given, using the procedure listed below. The preliminary results suggest that the knee joints of brittle mice do undergo a age-related type of bone and cartilage degeneration. The relationship of these changes to osteoarthritis needs further examination. Goals during the next year: We will continue to examine, compare, and characterize the structural changes observed in the knee joints of both the wild type and brittle mice imaged by micro-CT and Micro-MRI. Our plan is to determine the optimal resolution and orientation for joint assessment and measuring the changes in the cartilage and subchondral bone. To determine the dose of contrast material that will afford the most accurate and direct measure of relatedness to the articular cartilage. To establish parameters that will permit the establishment of a method that can be used reliably to record, catalog and standardize the radiographic interpretation of these images We will also pursue methods for establishing correlations between the histological sections and the MRI images.
