Background Two strains of guinea pig develop spontaneous osteoarthritis of the knee. Although the disease evolves at different rates in the two strains, it is not known whether these differences are reflected in the structure of the cartilage and cancellous bone. Questions/purposes We determined whether the threedimensional structure of the tibial-plateau cartilage and femoral cancellous bone differed between the two strains. Methods Six Dunkin-Hartley and six GOHI/SPF guinea pigs were evaluated. The animals were sacrificed at 11 months of age. The 24 proximal tibias were used for a stereologic histomorphometric analysis of the tibial-plateau cartilage. The 24 femurs were used for a site-specific, three-dimensional quantitative analysis of the cancellous bone by micro-CT. Results Compared to the GOHI/SPF guinea pigs, the tibial-plateau cartilage of the Dunkin-Hartley strain had a larger lesion volume (3.8% versus 1.5%) and a thicker uncalcified cartilage layer (0.042 versus 0.035 mm), but a thinner calcified cartilage zone (0.008 versus 0.01 mm) and a thinner subchondral cortical bone plate (0.035 versus 0.039 mm). The femoral cancellous bone in the DunkinHartley strain had a lower bone mineral density (477 versus 509 mg/cm 3 ). However, the trabeculae were thicker (3.91 versus 3.53 pixels) and farther apart (7.8 versus 5.6 pixels). The osteoarthritic changes in the cartilage were topographically mirrored in the subchondral bone. They were most severe on the medial side of the joint, particularly in the anterior region. Conclusions Spontaneous osteoarthritis in the guinea pig is associated with site-specific changes in the articular cartilage layer, which are topographically mirrored in the underlying subchondral bone. Clinical Relevance Three-dimensional structural information not revealed by two-dimensional radiography may help characterize the stages of osteoarthritis.

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