gms | German Medical Science

Objectives: For a long time, subchondral bone (SB) was considered to act as an impermeable barrier between articular cartilage (AC) and bone marrow. However, our high-resolution mapping of healthy human femoral heads revealed that SB is in fact perfused with an interconnected network of microchannels that directly connect the lowest margin of AC to the bone marrow (i.e. cartilage-bone marrow microchannel connectors; CMMC). Here we describe the location-dependent architecture of these CMMC, their correlation to the physiological loading of the joint, and discuss their potential significance in OA research.

Methods: A system was implemented to extract and scan 215 cartilage-bone biopsies from five healthy femoral heads (cadavers; age < 60). The location of the biopsies was standardized with respect to the normalized size of each joint, the long axis of femurs, and the distance of the biopsies to the geometrical center of the femoral heads. The biopsies (cylindrical; D=2.00 mm) were scanned at voxel size of 1.2 µm (µCT 50, SCANCO Medical AG, source voltage=90 kVp, intensity=88 µA), and were analyzed using a macro-based algorithm that computed the mean number of the CMMC (1/mm2), and their minimum and maximum size at the AC-SB interface. We hypothesized that the computed CMMC metrics are influenced by physiological local forces, which were estimated by a gait analysis performed on a healthy cohort with no pre-clinical signs of OA during self-paced walking. Accordingly, the CMMC metrics are reported and compared for three areas on the joint that are physiologically loaded differently. Statistical evaluation was carried out using SPSS package (IBM SPSS, version 25.0). The significance threshold (p) was set at 0.05.

Results and Conclusion: The highest number of the CMMC was detected at the load-bearing region of the femoral head (LBR; mean±SD, 9.85±3.26 1/mm2), which was significantly higher compared to the non-load-bearing region (NLBR; 4.08±1.58 1/mm2; p=0.002), and the peripheral rim (PR; 4.94±1.74 1/mm2; p=0.006) of the joint.On the other hand, the average maximum size of the CMMC was smallest at the LBR (55.04±4.2 µm) compared to the NLBR (74.25±9.34 µm; p=0.02), and PR (91.30±12.47 µm; p=0.0004), while the average minimum size showed a similar pattern (LBR, 36.22±2.28 µm; NLBR, 46.47±6.39; PR, 57.16±8.58 µm; p=0.003). We also found a significant positive correlation between local mean values of AC thickness and the CMMC number (Pearson's r=0.48, p<1e-13). We conclude that, (1) The traditional view that SB is a closed barrier should be reconsidered; (2) the architecture of CMMC is distinct based on the physiological biomechanical loading of the joint; and (3) CMMC have strong implications for bone-cartilage homeostasis, e.g. as possible passages for interstitial fluid movement, as SB-driven pathways to supply deeper chondrocytes with nutrition, and as a paradigm for biomechanical crosstalk between AC and SB.