Osteoarthritis (OA) is a progressing and complex disease that causes structural changes to the entire joint. Recent studies using 3D quantitative morphometric analysis (QMA) have shown that in situ micro-computed tomography (microCT) imaging can quantify structural changes of the whole joint in rabbit and rat anterior cruciate ligament transection models of OA [1,2]. Collagenase-induced OA (CIOA) is another OA model, and several studies observe structural changes related to disease. However, no previous research has measured these changes with disease progression nor looked at whole-joint morphometric changes in 3D. Forty-eight 10-week-old male C57BL/10 mice underwent OA induction via intra-articular collagenase injection at the knee, and a further 24 mice served as age-matched controls. Each week following the injection (up to 8-weeks), 9 mice (3 controls, 6 OA) were sacrificed, then scanned using microCT (vivaCT80, Scanco Medical). Scans were performed with a nominal voxel size of 10 μm. QMA measurements of joint centre of mass, as well as medial and lateral joint space width (JSWM, JSWL) and volume (JSVM, JSVL) were calculated. A two-factor ANOVA was used to determine the effect of time and disease. Results show that CIOA caused significant shift of the joint centre of mass in anterior/posterior and superior/inferior directions, along with increases in JSWM and JSWL, which were not affected by time. Meanwhile larger JSVM and JSVL, driven by both disease and time, were observed in CIOA samples from week 7. Typical joint space for each week is shown in Figure 1. These findings provide a preliminary insight into how CIOA causes structural change that should be further interrogated to identify links between biochemical and biomechanical triggers. Evaluation of histological data and semi-quantitative scores are planned, as well as repeating the experiment with more samples to identify statistically significant changes in morphometric markers linked to the CIOA model.