Can the presence of subchondral cyst - an indicator of subchondral bone disturbance, be used for subtyping knee osteoarthritis?

Abstract

PURPOSE: Subchondral bone cyst (SBC) is a pseudocystic lesion that is frequently reported in advanced osteoarthritis (OA), particularly in hip OA. Although it is considered as one of the cardinal radiological features in OA, and the presence of SBC in knee OA had been previously reported as a risk factor of cartilage loss and knee replacement, its clinical significance as a radiological feature in knee OA remains debated as they are hard to detect under plain radiographs. The actual aetiology of SBC is still unsolved but there are two main theories – the synovial fluid intrusion theory and bony contusion theory. The former suggests that intrusion of synovial fluid into the subchondral bone results in SBCs; while the latter states that unresolved bone marrow lesion (BML) could be the precursor of SBCs. More recent longitudinal studies show knee BMLs could progress into SBCs, cohering with the latter theory. The actual bone structural changes related to the presence of SBCs in knee subchondral bone are yet to be thoroughly investigated; therefore we have employed histology and μCT imaging to elucidate the relationship between SBC and surrounding trabecular bone remodelling activities in OA. We would like to look into changes in subchondral bone microstructures in relation to SBCs, the possible links between such changes with knee functions, as well the possibility of using this radiological marker for subtyping knee OA. METHODS: A total of 112 advanced OA patients (87 female and 25 male, aged between 48 and 87) undergoing total knee arthroplasty (TKA) were selected in the study. SBC diameter, surrounding trabecular bone parameters and bone mineral density were analyzed in μCT images. Paraffin sectioning of the resected tibial plateaux was performed with the thickness set at 7μm and subsequently stained with Haematoxylin & Eosin according to our previous protocols. Patients' knee functions are evaluated by our clinical staff based on the criteria of the Knee Society Knee Score. RESULTS: SBCs of diameters ranging from 3mm to 12.5mm were present in 73% of the study population, higher than 22.6% as detected by plain X-ray interpreted by our experienced surgeon, or 30% reported by Audrey et al. Trabecular bone in OA tibial plateaux with SBC underwent remodelling events, having a higher bone volume to tissue volume ratio (BV/TV) of 27.9 (±10.2)% compared to 14.2 (±5.9)% of their SBC-free counterparts; their bone mineral densities (BMD) are also significantly compromised (0.598 ±0.045 g/cmˆ3) compared the SBC-free specimens (0.623±0.048 g/cmˆ3). They also have higher trabecular number (1.6495 ±0.51039 mmˆ-1) compared to 1.4147±0.46550 mmˆ-1 of their SBC-free counterparts, and less trabecular separation (0.5060±0.19257mm verses 0.6186±0.25439mm). Subchondral bones with SBCs tend to be of lower BMD, have higher trabecular number and smaller spaces between trabeculae. From our histology slides, it was found that SBC is correlated to more chaotic de novo bone formation. Interestingly, we also found out high trabeular number and small trabecular separation, which are features associated with SBCs, are correlated with better pain score, indicating less pain in patients with SBCs. According to the histology sections, we have found specimens with SBCs have more bone in the marrow space than their SBC-free counterparts. These bones are, rather than lining on top of existing trabecular bones, clustered in the marrow space normally occupied by the marrow; although it is not yet clear whether these bones of poor quality are newly formed “de novo” bones or un-resorbed fragments due to bony contusion as a result of previous traumatic events. CONCLUSIONS: SBCs in knee OA were found to be more common than previously suggested, implying their presence had been vastly underestimated clinically. With lower BMD and higher bone volume, SBC could be an indicator for disturbance of subchondral bone metabolism; lower BMD, excessive de novo bone formation and uncoupled bone resorption – as observed in our histology. We have observed a potential correlation between uncoupled bone remodelling activity and the formation of SBC, and the presence of SBC could potentially indicate more severe osteoblastic dysfunction. To sum up, presence of SBCs indicates uncoupled subchondral bone remodelling in OA. SBCs are found to be more prevalent than previously suggested, implying their presence had been vastly underestimated. SBC-free tibal plateaux, despite having relatively preserved microstructure and higher mineral density, result in more painful knees. Our findings also provide clues that suggest subtyping knee OA by the presence of SBCs to guide future OA treatments.