Structural and Compositional Assessment of Bone and Articular Cartilage with Micro-Computed Tomography

Osteoarthritis is a degenerative joint disease that leads to debilitating pain and disability. The hallmark characteristics of OA are bone and cartilage degradation. An enigma present in the development of OA drugs and therapies is distinguishing which anatomical compartment, cartilage or subchondral bone, initiates the degenerative response and therefore would be the ideal target. A barrier in the preclinical field is a lack of an imaging technique that allows coordinated three-dimensional assessment of bone and cartilage in the same specimen with sufficient resolution to quantify structures (10 – 100 µm). To overcome this limitation, an imaging technique with high-resolution microcomputed tomography (µCT) was developed that is capable of quantifying structure and composition of both bone and cartilage in 3-D. This technique was utilized to attempt to answer which compartment, bone or cartilage, degrades first in the destabilization of the medial meniscus model (DMM). We characterized subchondral plate and articular cartilage structure and composition in the DMM model a few hours, 1, 2, 4 and 8 weeks post-DMM surgery. We also characterized alterations due to sham DMM surgery (no joint instability). The contralateral femur was used as a control in both experiments. In the DMM experiment, side differences were observed as early as 1 week after surgery. Similarly in the sham DMM experiment, side differences were observed by 1 week, but the effects on cartilage were greater than on bone. Thus, we could not conclude that degradation in one compartment preceded the other compartment. It is possible that the timescale examined in this study was too coarse to discriminate between the timing of the bone and cartilage responses or that both compartments react simultaneously.