Early Pathophysiology of Osteonecrosis

Abstract

Current concepts regarding the early pathophysiology of osteonecrosis (ON) are reviewed. Traumatic ON appears to result from arterial severance, an acute ischaemic event. Intravascular coagulation of the intraosseous microcirculation (capillaries and venous sinusoids) progressing to generalized venous thrombosis, and less commonly retrograde arterial occlusion, now appears to be the genesis of nontraumatic ON. However, a coagulopathy is only an intermediary event, which is always activated by some underlying aetiological risk factor(s). Conditions capable of triggering intravascular coagulation include familial thrombophilia (resistance to activated protein C, decreased protein C, protein S, or antithrombin III), hyperlipaemia and embolic lipid (alcoholism and hypercortisonism), hypersensitivy reactions (allograft organ rejection, immune complexes, and antiphospholipid antibodies), bacterial endotoxic (Shwartzman) reactions and various viral infections, proteolytic enzymes (pancreatitis), tissue factor release (inflammatory bowel disease, malignancies, neurotrauma, and pregnancy), and other prethrombotic and hypofibrinolytic conditions. In order to exceed the ischaemic threshold and produce ON, significant residual fibrin-platelet microthrombi must remain within the intraosseous vasculature for a minimum of two to six hours, and not be immediately removed by endogenous fibrinolysis. Hypofibrinolysis with increased plasminogen activator inhibitor has been found in patients with ON. The thrombotic threshold may be decreased in those hypercoagulable patients with hereditary thrombophilia, antiphospholipid antibodies, or hyperlipaemia. Subsequent exposure to an additional factor should facilitate intraosseous thrombosis and ON. It is also conceivable that fractional subchondral ON can cause both degenerative disc disease and “primary” osteoarthritis of aging and obesity.