Three-Dimensional Quantitative Morphometric Analysis (QMA) allows for reproducible and sensitive assessment of bone and joint in a preclinical mouse model of osteoarthritis

Abstract Evidence suggests that subchondral bone and whole joint structure features can be used as morphological markers associated with early-stage osteoarthritis (OA). A three-dimensional quantitative morphometric analysis (3D QMA) was previously established and demonstrated to reproducibly quantify subchondral bone and whole joint structure in small animal models. This work evaluates the reproducibility of this previously defined 3D QMA in a mouse model of OA and characterizes the osteoarthritic changes to subchondral bone and whole joint structure. Thirty-five male C57BL/10 mice aged nine weeks were recruited and divided evenly into five cross-sectional groups. Of these, fourteen ten-week-old mice were assigned to disease groups and underwent intra-articular injection of collagenase on the right knee joint to induce OA in the right tibiofemoral joint, and isotonic saline injected into the left contralateral knee joint. Animals were sacrificed at three time points (0, 4, and 8 weeks) and scanned ex vivo repeatedly for five times with micro-computed tomography (microCT). 3D QMA was performed, including subchondral cortical and epiphyseal bone measures, osteophyte detection and tibiofemoral joint metrics. The scan-rescan reproducibility of 3D QMA was tested on repeated microCT scans. Excellent reproducibility was obtained for all 3D QMA parameters, with ICC ranging from 0.771 to 0.999. Pathological changes caused by intra-articular injection of collagenase were characterized by measures of bone morphometry, osteophyte presence, as well as whole joint structure. Mechanical malalignment of tibiofemoral joint was observed in osteoarthritic joints, along with larger joint space width, reduced bone volume fraction, trabecular thinning predominantly in the lateral compartment, and osteophyte formation on medial joint margins.