SAT0566 Associations of osteoclasts and macrophages in subchondral bone with symptoms in people with knee oa
Authors: K. Aso, M. Shahtaheri, R. Hill, D. Wilson, D.A. Walsh
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Knee pain is a major source of disability and reason for hospital visits in patients with knee OA, but the pain pathophysiology is incompletely understood. Recent accumulating clinical evidence indicates that subchondral bone plays a role in generating joint pain in OA<sup>1</sup>. Subchondral bone marrow lesions (BMLs) detected on magnetic resonance imaging (MRI) in knee OA are strongly associated with pain<sup>1</sup>. In human OA histology, bone turnover and osteoclast numbers in subchondral bone were increased<sup>2</sup>. Inflammatory CD68-positive macrophages have been detected in bone marrow compartments of subchondral bone tissue from tibial plateaux of OA knees<sup>3</sup>. However, the relevance of osteoclasts and macrophage infiltration in subchondral bone to knee OA symptoms has not been clarified. <h3>Objectives</h3> To identify osteoclast and macrophage infiltration in subchondral bone associated with symptomatic knee OA, by comparing cases with similar macroscopic chondropathy, half of whom had sought help for knee pain and undergone total knee replacement (TKR) surgery (symptomatic chondropathy), the other half of whom had not sought help for knee pain but had died from unrelated illness (asymptomatic chondropathy). <h3>Methods</h3> Medial tibial plateaux were obtained from people undergoing TKR for OA (symptomatic chondropathy), and from post-mortem (PM) cases matched for similar macroscopic chondropathy scores (asymptomatic chondropathy). Samples were histologically graded for chondropathy, subchondral fibrovascular or macrophage infiltration, and TRAP-positive osteoclasts were quantified (figure 1). <h3>Results</h3> Patient demographics are shown in table 1. Total Mankin score showed similar values between the two groups (Table2). The number of osteoclasts in symptomatic chondropathy cases was significantly higher than in asymptomatic chondropathy cases (table 2). This difference remained significant (p&lt;0.05) after adjusting for age by logistic regression analysis. However, there was no significant difference in macrophage densities between symptomatic and asymptomatic chondropathy groups (Table 2). <h3>Conclusions</h3> Our results showed that not macrophages but osteoclast infiltration in subchondral bone were associated with symptomatic knee OA. Osteoclasts release protons that generate a local acidosis, which might be a potent activator of nociceptors leading to increased pain signaling<sup>4)</sup>. Increased osteoclast activity might be key features associated with bone pain in knee OA. <h3>References</h3> [1] Felson DT, Niu J, Guermazi A, et al. Correlation of the development of knee pain with enlarging bone marrow lesions on magnetic resonance imaging. Arthritis Rheum2007;56:2986–92. [2] Prieto-Potin I, Largo R, Roman-Blas JA, et al. Characterization of multinucleated giant cells in synovium and subchondral bone in knee osteoarthritis and rheumatoid arthritis. BMC Musculoskelet Disord2015Aug 27;16:226. [3] Geurts J, Patel A, Hirschmann MT, et al. Elevated marrow inflammatory cells and osteoclasts in subchondral osteosclerosis in human knee osteoarthritis. J Orthop Res2016Feb;34(2):262–9. [4] Jimenez-Andrade JM, Mantyh WG, Bloom AP, et al. Bone cancer pain. Ann N Y Acad Sci2010. <h3>Disclosure of Interest</h3> None declared