The pathophysiology of alveolar osteonecrosis of the jaw: anticardiolipin antibodies, thrombophilia, and hypofibrinolysis.
We studied 55 patients (50 women, 5 men) with severe facial pain and biopsy-proven neuralgia-inducing cavitational osteonecrosis (NICO) of the alveolar bone of the jaws. Our aim was to assess the pathophysiologic contributions to NICO of anticardiolipin antibodies (aCLA), thrombophilia (increased tendency to intravascular thrombi), and hypofibrinolysis (reduced ability to lyse thrombi). Of the 55 patients, 43 (78%) had one or more tests positive for thrombophilia or hypofibrinolysis (or both), and only 12 (22%) were normal. Eighteen of 55 (33%) patients had high aCLA (> 2 SD above mean value for control subjects); immunoglobulin G (IgG) (p = 0.01) and immunoglobulin A (IgA)(p = 0.001) levels were higher in patients than in controls. The distribution of elevated aCLA immunoglobulin classes among patients was as follows: IgG alone, 5 (9%); IgA alone, 7 (13%); and IgM alone, 3 (5%). Three patients (5%) had high levels of both IgG and IgA aCLA. Other defects of the thrombotic or fibrinolytic systems in the 55 patients included high lipoprotein(a) in 36% (vs 20% in control subjects (p = 0.03)), low stimulated tissue plasminogen activator activity (tPA-Fx) in 22% (vs 7% in control subjects (p = 0.08)), high plasminogen activator inhibitor activity (PAI-Fx) in 18% (vs 8% in control subjects (p = 0.03)), resistance to activated protein C in 16% (vs 0% in control subjects (p = 0.007)), low antigenic protein C in 4+ (vs 0% in control subjects (p > 0.2)), and low antigenic protein S in 4% (vs 0% in control subjects (p > 0.2)). Anticardiolipin antibodies and other defects of the thrombotic and fibrinolytic systems appear to be common, potentially reversible pathogenetic risk factors associated with osteonecrosis of the jaw.
Gruppo
R
R
Division of Hematology/Oncology, Children's Hospital Medical Center, Cincinnati, OH USA.
Glueck
C J
CJ
McMahon
R E
RE
Bouquot
J
J
Rabinovich
B A
BA
Becker
A
A
Tracy
T
T
Wang
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000539:Alveolar Process; D017153:Antibodies, Anticardiolipin / Q000097:blood*; D005157:Facial Pain; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007571:Jaw Diseases / Q000209:etiology / Q000276:immunology / Q000473:pathology; D017270:Lipoprotein(a) / Q000097:blood; D008297:Male; D008875:Middle Aged; D010020:Osteonecrosis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D011486:Protein C / Q000378:metabolism; D013927:Thrombosis / Q000150:complications*; D010959:Tissue Plasminogen Activator / Q000378:metabolism
D017153:Antibodies, Anticardiolipin; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D017270:Lipoprotein(a); D011486:Protein C; D010959:Tissue Plasminogen Activator