A high‐resolution cross‐species comparative analysis of the subchondral bone provides insight into critical topographical patterns of the osteochondral unit

Location-dependent OA development,1 topographical differences within individual subregions,2,3 all influenced by the meniscus coverage2,3 highlight the urgent need to precisely reproduce pathological alterations at high quantitative detail in appropriate in vivo models.4,5 We performed a detailed comprehensive analysis of the zonal characteristics of the subchondral bone of mice, rats, rabbits, minipigs, and sheep, the most common animal models in orthopaedic research, applying the human tibial plateau as a model (Figure 1A), to identify the species with the highest morphological agreement. Minipigs, in contrast, had expanded trabeculae in the lateral tibial plateau. Since the medial tibiofemoral compartment is involved in 67% of all OA cases, and the load distribution can be (non)surgically modified,7 such lateral-medial dissimilarities are of major translational relevance. The subarticular spongiosa displays structural lateral-to-medial differences in humans, sheep, rats and minipigs, largely absent in rabbits and mice. (iv) Most of the osteochondral parameters show strong and significant correlations with joint size. (v) The declining rate of analogy in macroscopic anatomy and microstructure of the tibial plateau of the animal species to humans is: sheep ≈ minipigs > rabbits > > rats > > mice.