Whole bone µCT 3-dimensional mapping reveals new early imaging biomarkers of osteoarthritis

To characterize the deviation from normal bone architectural patterns in OA using an innovative, 3D whole bone mapping approach that utilises micro-computed tomography (µCT) scans of femoral heads from normal and naturally osteoarthritic dogs. Ex-vivo high-resolution µCT 3D mapping of normal (n=28) and OA (n=36) canine femoral heads exploited segmentation of each entire epiphysis into eight anatomically defined volumes, each sub-segmented into subchondral bone (SCB) plate and trabecular bone. Micro-architecture in sub-segmented regions were also spatially-registered to overlying cartilage damage severity and statistical evaluated, including principal component analysis and mixed-effect modelling. Normal femoral heads demonstrated spatially conserved concentric and quadrant-based patterns of bone micro-architecture, including greater central trabecular anisotropy (DA; median central DA 0.40-0.44 vs peripheral DA 0.30-0.35) and quadrant-dependent variation in subchondral bone plate thickness, which was greatest in the caudo-medial quadrant (median 0.517 mm vs 0.254 mm in the cranio-lateral quadrant centrally). Osteoarthritic femoral heads showed altered micro-architectural patterns, characterised by central osteosclerosis with peripheral osteopenia, reduced central trabecular anisotropy (mean difference versus normal 0.086-0.117, depending on segment), and increased subchondral bone plate closed porosity (mean difference versus normal up to 0.62%), with spatial associations to cartilage damage severity. When modelled against osteoarthritis severity, reduced central trabecular anisotropy distinguished normal cartilage from all levels of cartilage damage, while increasing peripheral subchondral bone plate closed porosity stratified increasing cartilage damage severity. Whole bone 3D µCT mapping of femoral heads from a large animal that develops OA spontaneously revealed spatially conserved regional patterns of femoral head micro-architecture that are not detectable using focal or two-dimensional sampling approaches. Changes in these patterns, particularly reduced central trabecular anisotropy and increased subchondral bone plate porosity, distinguished both the presence and severity of cartilage damage respectively, identifying these features as candidate imaging biomarkers of osteoarthritis.