Increased nerve growth factor expression and osteoclast density are associated with subchondral bone marrow lesions in osteoarthritic knees

Abstract Background Subchondral bone marrow lesions (BMLs) detected on MRI in knee osteoarthritis (OA) are associated with knee pain. However, the pain mechanisms of BMLs are unknown. Increased nerve growth factor (NGF) expression at the osteochondral junction and increased osteoclast density in subchondral bone appear to be key features associated with bone pain in knee OA. Therefore, in this study, we aimed to identify the association of NGF and osteoclasts with BMLs in knee OA. Methods Twenty tibial plateaus were obtained from patients undergoing total knee arthroplasty for medial knee OA with BML at the medial tibia plateau (MTP). Osteochondral tissue with and without BML from the weight-bearing area in the MTP and without BML from the weight-bearing area in the lateral tibial plateau (LTP) was collected. Osteoarthritis bone score, Mankin score, NGF expression and density of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts were compared among the three osteochondral tissues. Results The osteoarthritis bone score, total Mankin score, NGF-expressed area and osteoclast density of the subchondral bone with BML in MTP were significantly higher than those of subchondral bone without BML in MTP and subchondral bone without BML in LTP. The mean differences of NGF-expressed area and osteoclast density between subchondral bone with BML and without BML in MTP were 9.0% (95% confidence intervals (CI): 5.9–12.1%) and 0.6 osteoclasts/mm (95% CI: 0.3–0.9%), respectively. In sections from subchondral tissue with BML in MTP, NGF immunoreactivity was detected in multinucleate osteoclasts, fibroblast-like cells, mononuclear cells and cartilage islands in the bone marrow space. Conclusions Increased NGF expression and osteoclast density are associated with subchondral BMLs in knee OA. This study will contribute to understanding the mechanisms of BML-related pain in OA and identifying new therapeutic targets for the management of bone pain in knee OA.