Abstract
ObjectiveThe degradation of articular cartilage, which characterises osteoarthritis (OA), is usually paired with excessive bone remodelling, including subchondral bone sclerosis, cysts, and osteophyte formation. Experimental models of OA are widely used to investigate pathogenesis, yet few validated methodologies for assessing periarticular bone morphology exist and quantitative measurements are limited by manual segmentation of micro-CT scans. The aim of this work was to chart the temporal changes in periarticular bone in murine OA by novel, automated micro-CT methods.MethodsOA was induced by destabilisation of the medial meniscus (DMM) in 10-week old male mice and disease assessed cross-sectionally from 1- to 20-weeks post-surgery. A novel approach was developed to automatically segment subchondral bone compartments into plate and trabecular bone in micro-CT scans of tibial epiphyses. Osteophyte volume, as assessed by shape differences using 3D image registration, and by measuring total epiphyseal volume was performed.ResultsSignificant linear and volumetric structural modifications in subchondral bone compartments and osteophytes were measured from 4-weeks post-surgery and showed progressive changes at all time points; by 20 weeks, medial subchondral bone plate thickness increased by 160±19.5 μm and the medial osteophyte grew by 0.124±0.028 μm3. Excellent agreement was found when automated measurements were compared with manual assessments.ConclusionOur automated methods for assessing bone changes in murine periarticular bone are rapid, quantitative, and highly accurate, and promise to be a useful tool in future preclinical studies of OA progression and treatment. The current approaches were developed specifically for cross-sectional micro-CT studies but could be applied to longitudinal studies.
Highlights
Osteoarthritis (OA) is the most prevalent joint disease; an incurable and painful condition that is a leading cause of disability worldwide
Significant linear and volumetric structural modifications in subchondral bone compartments and osteophytes were measured from 4-weeks post-surgery and showed progressive changes at all time points; by 20 weeks, medial subchondral bone plate thickness increased by 160±19.5 μm and the medial osteophyte grew by 0.124±0.028 μm3
Despite plate sclerosis (Fig 5A and 5B) and trabecular bone remodelling (Fig 5D), we found no differences in bone mineral density (BMD) between operated and non-operated joints in either of the compartments (Fig 5E and 5F); these were only noted within compartments at early and late time points of disease
Summary
Osteoarthritis (OA) is the most prevalent joint disease; an incurable and painful condition that is a leading cause of disability worldwide. Excessive bone remodelling has been linked to cartilage degeneration [4, 5] and pain [6] from early on in disease [7], but the nature of the relationship between both tissues and how lesions progress over time remains unclear [8, 9]. Despite osteophytes being a well-established feature of osteoarthritic joints, there seems to be a lack of validated methods for measuring these bony structures Assessment in both clinical [12] and experimental models [25] has been often limited to semi-quantitative grading based on their size and maturity, but micro-CT scans have been shown to have the potential to provide volumetric measurements of osteophytes [26]
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