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

A high-resolution cross-species comparative analysis of the subchondral bone provides insight into critical topographical patterns of the osteochondral unitDear Editor, Deciphering the hierarchical and species-specific topographical structure of the subchondral bone has far-reaching implications.The subchondral bone is in the focus of many pathological conditions, including osteoarthritis (OA).Location-dependent OA development, 1 topographical differences within individual subregions, 2,3 all influenced by the meniscus coverage 2,3 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.Macroscopic morphology was largely conserved (Figure 1B-F; Figure S1).The groove of the extensor digitorum longus tendon was present only in sheep, minipigs, and rabbits (Figure 1B,C; Figure S1).Normalized ratios of anatomical landmarks were highly similar in the larger species (Figure 1D-F; Figure S1).Humans had an extremely thin, porous and less compact subchondral bone plate (SCBP), similar in many characteristics to rabbits and minipigs, strikingly different from rats and mice (Figure 1G-N; Figure S2).Solely in larger species (humans, sheep, minipigs; partly in rabbits), the SCBP was thinner under the meniscus-covered peripheral areas than in the not meniscus-covered central area (Figure 1H), a finding highly relevant for translational studies, for example, examining OA induction by meniscus tears.Of note, mice and rats did not exhibit such pattern.Multivariate analyses of all SCBP parameters characterized minipigs and rabbits as most similar to humans, followed by sheep, rats and mice (Figure 1M,N; Figure S2D).