3D profiling of mouse epiphyses across ages reveals new potential imaging biomarkers of early spontaneous osteoarthritis.

Worldwide research groups and funding bodies have highlighted the need for imaging biomarkers to predict osteoarthritis (OA) progression and treatment effectiveness. Changes in trabecular architecture, which can be detected with non-destructive high-resolution CT imaging, may reveal OA progression before apparent articular surface damage. Here, we analysed the tibial epiphyses of STR/Ort (OA-prone) and CBA (healthy, parental control) mice at different ages to characterise the effects of mouse age and strain on multiple bony parameters. We isolated epiphyseal components using a semi-automated method, and measured the total epiphyseal volume; cortical bone, trabecular bone and marrow space volumes; mean trabecular and cortical bone thicknesses; trabecular volume relative to cortical volume; trabecular volume relative to epiphyseal interior (trabecular BV/TV); and the trabecular degree of anisotropy. Using two-way ANOVA (significance level ≤0.05), we confirmed that all of these parameters change significantly with age, and that the two strains were significantly different in cortical and trabecular bone volumes, and trabecular degree of anisotropy. STR/Ort mice had higher cortical and trabecular volumes and a lower degree of anisotropy. As the two mouse strains reflect markedly divergent OA predispositions, these parameters have potential as bioimaging markers to monitor OA susceptibility and progression. Additionally, significant age/strain interaction effects were identified for total epiphyseal volume, marrow space volume and trabecular BV/TV. These interactions confirm that the two mouse strains have different epiphyseal growth patterns throughout life, some of which emerge prior to OA onset. Our findings not only propose valuable imaging biomarkers of OA, but also provide insight into ageing 3D epiphyseal architecture bone profiles and skeletal biology underlying the onset and development of age-related OA in STR/Ort mice.

Structural clues to articular calcified cartilage function: A descriptive review of this crucial interface tissue.

Articular calcified cartilage (ACC) has been dismissed, by some, as a remnant of endochondral ossification without functional relevance to joint articulation or weight-bearing. Recent research indicates that morphologic and metabolic ACC features may be important, reflecting knee joint osteoarthritis (OA) predisposition. ACC is less investigated than neighbouring joint tissues, with its component chondrocytes and mineralised matrix often being either ignored or integrated into analyses of hyaline articular cartilage and subchondral bone tissue respectively. Anatomical variation in ACC is recognised between species, individuals and age groups, but the selective pressures underlying this variation are unknown. Consequently, optimal ACC biomechanical features are also unknown as are any potential locomotory roles. This review collates descriptions of ACC anatomy and biology in health and disease, with a view to revealing its structure/function relationship and highlighting potential future research avenues. Mouse models of healthy and OA joint ageing have shown disparities in ACC load-induced deformations at the knee joint. This raises the hypothesis that ACC response to locomotor forces over time may influence, or even underlie, the bony and hyaline cartilage symptoms characteristic of OA. To effectively investigate the ACC, greater resolution of joint imaging and merging of hierarchical scale data will be required. An appreciation of OA as a 'whole joint disease' is expanding, as is the possibility that the ACC may be a key player in healthy ageing and in the transition to OA joint pathology.

A new straightforward method for semi-automated segmentation of trabecular bone from cortical bone in diverse and challenging morphologies.

Many physiological, biomechanical, evolutionary and clinical studies that explore skeletal structure and function require successful separation of trabecular from cortical compartments of a bone that has been imaged by X-ray micro-computed tomography (micro-CT) prior to analysis. Separation often involves manual subdivision of these two similarly radio-opaque compartments, which can be time-consuming and subjective. We have developed an objective, semi-automated protocol which reduces user bias and enables straightforward, user-friendly segmentation of trabecular from the cortical bone without requiring sophisticated programming expertise. This method can conveniently be used as a 'recipe' in commercial programmes (Avizo herein) and applied to a variety of datasets. Here, we characterize and share this recipe, and demonstrate its application to a range of murine and human bone types, including normal and osteoarthritic specimens, and bones with distinct embryonic origins and spanning a range of ages. We validate the method by testing inter-user bias during the scan preparation steps and confirm utility in the architecturally challenging analysis of growing murine epiphyses. We also report details of the recipe, so that other groups can readily re-create a similar method in open access programmes. Our aim is that this method will be adopted widely to create a reproducible and time-efficient method of segmenting trabecular and cortical bone.