Associations of Symptomatic Knee Osteoarthritis With Histopathologic Features in Subchondral Bone.

Koji Aso,Deborah Wilson,Roger Hill,S Mohsen Shahtaheri,David A Walsh,Daniel F Mcwilliams

doi:10.1002/art.40820

Abstract

Subchondral bone and the osteochondral junction are thought to contribute to osteoarthritis (OA) knee pain. We undertook this study to identify osteochondral pathologies specifically associated with symptomatic human knee OA. Medial tibial plateau samples from 2 groups of subjects (n = 31 per group) were matched for macroscopic chondropathy scores. The symptomatic chondropathy group had undergone total knee replacement for OA knee pain, at which time specimens of the medial tibial plateau were obtained. The asymptomatic chondropathy group included subjects who died of unrelated illness (specimens were obtained at postmortem examination) and who had not previously sought help for knee pain. OA histopathology, immunoreactivity for nerve growth factor (NGF) and CD68 (macrophages), tartrate-resistant acid phosphatase-positive subchondral osteoclasts, and synovitis were compared between groups. Mankin scores, subchondral bone density, and subchondral CD68-immunoreactive macrophage infiltration were similar between the 2 groups. NGF-like immunoreactivity was found in subchondral mononuclear cells and osteoclasts, as well as in chondrocytes. NGF in osteochondral channels and osteoclast densities in subchondral bone were higher in the symptomatic chondropathy group than in the asymptomatic chondropathy group (P < 0.01 and P = 0.02, respectively), as 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 adjustment for age and synovitis score (P = 0.01 and P = 0.04, respectively). Osteochondral NGF and osteoclast densities, together with synovitis scores, explained ~28% of sample allocation to symptomatic or asymptomatic groups. Subchondral pathology was associated with symptomatic knee OA, independent of chondropathy and synovitis. Increased NGF expression in osteochondral channels and increased osteoclast density appear to be key features associated with bone pain in knee OA.

Highlights

Pain is the major source of disability and reason for hospital visits in patients with knee osteoarthritis (OA)
nerve growth factor (NGF) expression in osteochondral channels was associated with symptomatic knee OA after adjusting for osteoclast density, but association of osteoclasts density with symptoms did not persist after adjusting for NGF
Our results showed that 28% of group allocation to symptomatic and asymptomtic chondropathy can be explained by the combination of synovitis score, NGF expression in osteochondral channels and subchondral osteoclast density

Summary

Introduction

Pain is the major source of disability and reason for hospital visits in patients with knee osteoarthritis (OA). Recent evidence suggests that subchondral bone contributes to knee OA pain[1,2,3,4,5,6,7]. Subchondral bone marrow lesions (BMLs) detected on magnetic resonance imaging (MRI) in knee OA are strongly associated with pain[1,2,3,4, 7]. A flattening or depression of the subchondral bone visualised using x-rays or MRI, is associated with the presence of pain[5, 6]. Microarray analysis of BMLs in OA demonstrated upregulation of genes implicated in neurogenesis, osteochondral turnover and inflammation that might contribute to OA pain[8]. The mechanisms by which subchondral pathology contribute to OA pain are incompletely understood

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