Weijia William Lu describes for SIIC his article published in Osteoarthritis and Cartilage 23(12):2174-2183, December 2015

Hong Kong, China (special for SIIC)
Osteoarthritis (OA) is one of the most prevalent joint disorders characterized by articular cartilage attrition and joint pain. Subchondral bone cysts (SBCs) were first defined as a concentric arrangement of trabeculae around an enlarged marrow space on radiographs. The presence of SBCs is associated with knee pain, joint disability, cartilage loss, and increased risk of knee replacement in OA. Two theories were supposed to explain the formation of SBCs: the “fluid breach theory”, and the “bony contusion theory” which claimed that, in the region of subchondral bone where the overloading exceeds the limits of physiological endurance, the bone dies and is liquefied. However, histopathology evaluation of cartilage and bone remodeling in SBCs within human knee OA are still poorly understood. Investigation of associations among bone remodeling and structure and cartilage in SBC regions will contribute to knowledge of OA pathogenesis.

Tibial plateaus (n = 97) were collected from knee OA patients during total knee arthroplasty. SBCs were identified using micro-computed tomography, and the specimens were divided into non-cyst (n = 25) and bone cyst (n = 72) groups. Microstructure of subchondral bone was assessed using bone volume fraction (BV/TV), trabecular number (Tb.N), structure model index (SMI) and bone mineral density (BMD). In bone cyst group, the cyst subregion, which contained at least one cyst, and the peri-cyst subregion, which contained no cysts, were further selected for microstructure analysis. Articular cartilage damage was estimated using the OARSI score. The numbers of TRAP+ osteoclasts, Osterix+ osteoprogenitors, Osteocalcin+ osteoblasts and expression of SOX9 were evaluated by immunohistochemistry.

We found that bone cyst group presented higher BV/TV, Tb.N and SMI at subchondral bone than non-cyst group. Furthermore, cyst subregion displayed increased BV/TV and Tb.N but lower BMD and SMI than peri-cyst subregion. Histology revealed a higher OARSI score in bone cyst group. SBC exhibited a weak relationship with BV/TV, etc. The numbers of TRAP+ osteoclasts, Osterix+ osteoprogenitors, Osteocalcin+ osteoblasts and expression of SOX9, were higher in bone cyst group.

In this study, we investigated changes in bone remodeling, bone structure and articular cartilage associated with SBCs within human knee OA. We found that bone and articular cartilage demonstrate changes localized to SBC regions. These findings support the paradigm of focal interactions among bone, marrow, and articular cartilage in pathogenesis of knee OA.

There are several limitations of this study. First, this is a cross-sectional study. Thus, we were not able to monitor subchondral bone turnover and cartilage damage during cyst development longitudinally. Second, the patients recruited in this study had moderate-to-severe knee OA. Therefore, the results could not represent the conditions in earlier stages of human OA. Third, in the present study, the bone and cartilage samples were extracted from the center of the load-bearing area of the tibial plateau. However, SBCs and the corresponding bone turnover and cartilage degradation in other regions of the tibial plateau may differ. Fourth, reports from arthroplasty registries showed that gender distribution of knee OA patients varies among different countries. In a South Korea study, female patients comprised as high as 88.1%-88.9% of the total sample of knee OA patients. Similarly, in the authors’ hospital, it has been reported that the female patients comprised 79.2%-85.5% of the total sample of knee OA patients. In the current study, 88.7% of the patients were female. Thus, the gender of patients was skewed toward females, and males were underrepresented. In addition, this skewed gender distribution, together with other characteristics, limits the interpretation of the results to certain cohorts of patients, such as Asians versus other ethnic groups. Last but not least, only SBCs with diameters greater than 1 mm were included in this study, because it is difficult to precisely differentiate between very small SBCs and bone marrow space using micro-CT. Thus, this study may underestimate the effects of SBCs, and lead to the relatively weak relationships (r2 < 0.30) between SBC volume and parameters of subchondral bone and cartilage damage.

Taken together, we found that SBC regions in human OA knees are foci of increased bone remodeling and altered structure, and are spatially associated with articular cartilage degradation. These results imply the biomechanical link between SBC formation and cartilage damage. Our further analyses provide a “bone remodeling” model for SBC formation: due to mechanical stimulus or/and biochemical micro-environment changes, the remodeling of subchondral bone is activated. Necrotic bone fragments are phagocytosed by osteoclasts, creating the cyst cavity. Meanwhile, bone formation is enhanced by endochondral bone formation as well as increased activity of osteoprogenitors and osteoblasts, resulting in a sclerotic cyst wall. This model favors the “bony contusion theory”. Thus, our findings prompt the need for a longitudinal study to confirm the “bone remodeling” model for SBC formation and its causal relationship with articular cartilage degeneration.