OBJECTIVES: Our specific aim in 49 patients (42 women, 7 men) with osteonecrosis of the jaw was to determine whether thrombophilia (increased tendency to intravascular thrombosis) or hypofibrinolysis (reduced ability to lyse thrombi) were associated with this regional avascular necrosis. STUDY DESIGN: Determinants of thrombosis and fibrinolysis were compared in healthy controls and in 42 women and 7 men who had biopsy-proven idiopathic osteonecrosis of the jaw with severe chronic jaw or facial pain syndromes and failure to respond to conventional medical and dental treatments. RESULTS: Of the 49 patients, 35 (71%) had thrombophilia or hypofibrinolysis and only 14 were normal. Thrombophilia as a sole coagulation defect was found in 10 patients, 7 with resistance to activated protein C and 3 with low protein C (deficiency of an antithrombotic protein). Hypofibrinolysis with low stimulated tissue plasminogen activator activity and high lipoprotein (a) (an atherogenic, hypofibrinolytic lipoprotein) were found as sole coagulation defects in seven and eight patients, respectively. Ten patients had mixed defects; 7 of these 10 had thrombophilia with resistance to activated protein C. Sinusoidal dilatation was a constant feature in maxillary and mandibular bone biopsies, suggesting venous occlusion with intramedullary hypertension. Marrow fibrosis and occasional fibrin plugs were additional microscopic features believed to impair venous drainage and to contribute to ischemic necrosis of the alveolar bone. CONCLUSIONS: Primary thrombophilia and hypofibrinolysis appear to be common, heritable, pathophysiologic risk factors for idiopathic osteonecrosis of the jaws. These coagulation defects may also contribute to alveolar neuralgia, atypical odontalgia and facial neuralgia, idiopathic trigeminal neuralgia, and to treatment failures so often encountered in patients with alveolar osteonecrosis and disabling chronic facial and jawbone pain syndromes.
OBJECTIVES: Our specific aim in 49 patients (42 women, 7 men) with osteonecrosis of the jaw was to determine whether thrombophilia (increased tendency to intravascular thrombosis) or hypofibrinolysis (reduced ability to lyse thrombi) were associated with this regional avascular necrosis. STUDY DESIGN: Determinants of thrombosis and fibrinolysis were compared in healthy controls and in 42 women and 7 men who had biopsy-proven idiopathic osteonecrosis of the jaw with severe chronic jaw or facial pain syndromes and failure to respond to conventional medical and dental treatments. RESULTS: Of the 49 patients, 35 (71%) had thrombophilia or hypofibrinolysis and only 14 were normal. Thrombophilia as a sole coagulation defect was found in 10 patients, 7 with resistance to activated protein C and 3 with low protein C (deficiency of an antithrombotic protein). Hypofibrinolysis with low stimulated tissue plasminogen activator activity and high lipoprotein (a) (an atherogenic, hypofibrinolytic lipoprotein) were found as sole coagulation defects in seven and eight patients, respectively. Ten patients had mixed defects; 7 of these 10 had thrombophilia with resistance to activated protein C. Sinusoidal dilatation was a constant feature in maxillary and mandibular bone biopsies, suggesting venous occlusion with intramedullary hypertension. Marrow fibrosis and occasional fibrin plugs were additional microscopic features believed to impair venous drainage and to contribute to ischemic necrosis of the alveolar bone. CONCLUSIONS:Primary thrombophilia and hypofibrinolysis appear to be common, heritable, pathophysiologic risk factors for idiopathic osteonecrosis of the jaws. These coagulation defects may also contribute to alveolar neuralgia, atypical odontalgia and facial neuralgia, idiopathic trigeminal neuralgia, and to treatment failures so often encountered in patients with alveolar osteonecrosis and disabling chronic facial and jawbone pain syndromes.
Authors: Regina Landesberg; Victoria Woo; Serge Cremers; Matthew Cozin; Darja Marolt; Gordana Vunjak-Novakovic; Stavroula Kousteni; Srikala Raghavan Journal: Ann N Y Acad Sci Date: 2011-02 Impact factor: 5.691