Associations of symptomatic knee Osteoarthritis with histopathologic features in subchondral bone.
OBJECTIVES: Subchondral bone and the osteochondral junction are thought to contribute to osteoarthritis (OA) knee pain. We aimed to identify osteochondral pathologies specifically associated with symptomatic human knee OA. METHODS: Two groups of medial tibial plateau (n=31 per group) were matched for macroscopic chondropathy scores. One group had undergone total knee replacement for OA knee pain (symptomatic chondropathy). The other had not sought help for knee pain and died from unrelated illness (asymptomatic chondropathy). OA histopathology, immunoreactivity for nerve growth factor (NGF) and CD68 (macrophages), tartrate resistant acid phosphatase (TRAP)-positive subchondral osteoclasts and synovitis were compared between groups. RESULTS: Mankin score, subchondral bone density and subchondral CD68-immunoreactive macrophage infiltration were similar between the 2 groups. NGF-like immunoreactivity was in subchondral mononuclear cells and osteoclasts, as well as in chondrocytes. NGF in osteochondral channels, and osteoclast densities in subchondral bone were higher in symptomatic than in asymptomatic chondropathy groups (NGF; p<0.01, TRAP; p=0.02), as also were synovitis scores (p<0.01). Osteochondral pathology was not significantly associated with synovitis score. The differences in NGF expression and in osteoclast density remained significant after adjusting for age and synovitis score (NGF; p=0.01, TRAP; p=0.04). Osteochondral NGF and osteoclast densities, together with synovitis scores, explained approximately 28% of sample allocation to symptomatic or asymptomatic groups. CONCLUSION: Subchondral pathology was associated with symptomatic knee OA independently of chondropathy and synovitis. Increased NGF expression in osteochondral channels, and osteoclast density appear be key features associated with bone pain in knee OA.
- Rheumatology 
Walsh, David A