Vascular mechanisms in osteoarthritis.

Superficial injury and fibrillation of articular cartilage as a consequence of ageing, genetic, hormonal or mechanical factors are not necessarily associated with joint pain. However, failure of joint cartilage accompanied by synovitis and abnormalities in subchondral bone and its vasculature generally is, the syndrome being known as osteoarthritis. We suggest that the progression of early cartilage fibrillation to symptomatic OA arises initially as a consequence of the release into synovial fluid of cartilage-derived antigens that activate joint lining macrophages and circulating leukocytes, thereby establishing a synovitis. Pro-inflammatory mediators and pro-coagulant factors etc. not only perpetuate cartilage destruction but also promote a state of hypercoagulation, hypofibrinolysis, thrombosis and ischaemic bone necrosis at compromised sites such as in the subchondral vasculature. These events are augmented by ageing and associated hormonal changes. On the basis of this hypothesis we suggest that anti-thrombotic/anti-lipidaemic agents that also exhibit anti-inflammatory activity could be effective anti-osteoarthritic drugs. Experimental studies are described which support this proposal.

Hypercoagulability and hypofibrinolysis in primary osteoarthritis.

Histologic evidence of venous thrombosis and lipid abnormalities have previously been reported in osteoarthritis. Hypofibrinolysis has been recorded in patients with ischemic necrosis of bone, and it has been proposed as a major cause of osteonecrosis. This study determines whether systemic evidence of coagulation and lipid abnormalities could be detected in osteoarthritis. Global and specific tests were used to assess coagulability and fibrinolysis in 44 patients with degenerative osteoarthritis of the hip and 52 matched control subjects. In patients with osteoarthritis, an increase in factor VIIlc, increased platelet sensitivity over a range of adenosine diphosphate concentrations (0.05 micromol/L-4 micromol/L) and elevated D dimer levels were found. Euglobulin clot lysis time was prolonged in this group and plasminogen activator inhibitor Type 1 activity was increased. Relative hyperlipidemia was observed in the osteoarthritis group, with increased cholesterol, low density lipoprotein cholesterol, and triglyceride levels. It is concluded that there is a hypercoagulable and prothrombotic condition in osteoarthritis, with hypofibrinolysis and indirect evidence of increased fibrin generation. The possible contribution of lipid abnormalities to hemostatic imbalance in osteoarthritis is discussed.

Intraosseous thrombosis in ischemic necrosis of bone and osteoarthritis.

It has been proposed that nontraumatic ischemic necrosis of bone (INB) is a result of lipid associated intraosseous thrombosis. A histological study of 15 patients with INB confirmed the presence of intravascular lipid and thrombosis in the vessels of the femoral head. A similar analysis of 11 patients with primary osteoarthritis (OA) showed similar changes at lower levels. These changes were not observed in seven control femoral heads. The possibility that both INB and OA result from intraosseous thrombosis is discussed.