Role of vascular channels as a novel mechanism for subchondral bone damage at cruciate ligament entheses in osteoarthritis and inflammatory arthritis

Abstract

ObjectivesThe purpose of this work was to test whether normal peri-entheseal vascular anatomy at anterior and posterior cruciate ligaments (ACL and PCL) was associated with distribution of peri-entheseal bone erosion/bone marrow lesions (BMLs) in inflammatory arthritis (IA) and osteoarthritis (OA).MethodsNormal microanatomy was defined histologically in mice and by 3 T MRI and histology in 21 cadaveric knees. MRI of 89 patients from the Osteoarthritis Initiative and 27 patients with IA was evaluated for BMLs at ACL and PCL entheses. Antigen-induced arthritis (AIA) in mice was evaluated to ascertain whether putative peri-entheseal vascular regions influenced osteitis and bone erosion.ResultsVascular channels penetrating cortical bone were identified in knees of non-arthritic mice adjacent to the cruciate ligaments. On MRI of normal cadavers, vascular channels adjacent to the ACL (64% of cases) and PCL (71%) entheses were observed. Histology of 10 macroscopically normal cadaveric specimens confirmed the location of vascular channels and associated subclinical changes including subchondral bone damage (80% of cases) and micro-cyst formation (50%). In the AIA model, vascular channels clearly provided a site for inflammatory tissue entry and osteoclast activation. MRI showed BMLs in the same topographic locations in both patients with early OA (41% ACL, 59% PCL) and IA (44%, 33%).ConclusionThe findings show that normal ACL and PCL entheses have immediately adjacent vascular channels which are common sites of subtle bone marrow pathology in non-arthritic joints. These channels appear to be key determinants in bone damage in inflammatory and degenerative arthritis.

MRI texture analysis of subchondral bone at the tibial plateau

“…Previous MR studies have demonstrated alterations in microstructural trabecular morphometry measurements between volunteers and individuals with OA [13,14], and that such measurements correlate well with severity of OA [15]. Proposed mechanisms of alteration in SB architecture include entry of inflammatory infiltrates via vascular channels in the SB [37] and increased deposition of subchondral marrow lipids [38].…”

Recent advances in the understanding of molecular mechanisms of cartilage degeneration, synovitis and subchondral bone changes in osteoarthritis

“…Chemokines, cytokines, and proteases secreted by chondrocytes have been implicated in the alteration of biochemical and functional abilities of the osteoblasts within subchondral bone. For example, IL-6 in combination with other cytokines such as IL-1β can switch osteoblasts from a normal phenotype to a sclerotic phenotype (162,163). There is increasing evidence that the Wnt signaling pathway is a key regulator of subchondral bone and is implicated in OA (164).…”

“…Secretion of angiogenic factors such as VEGF increases vascularity within the deep layers of articular cartilage, thus facilitating molecular transport. Recently, the communication pathways of cartilage effect on bone reported includes microcracks, neovascularization, vascular channels next to the cruciate ligaments, in addition, small molecules diffusion directly (161,162). Chemokines, cytokines, and proteases secreted by chondrocytes have been implicated in the alteration of biochemical and functional abilities of the osteoblasts within subchondral bone.…”

Imaging research results from the Osteoarthritis Initiative (OAI): a review and lessons learned 10 years after start of enrolment

“…They also were associated with risk of subsequent KR 73. Further, vascular channels were suspected to be involved in the mechanism by which damage occurs to subchondral bone108…”