The 2003 Marshall R. Urist Award Paper - Genetic background of osteonecrosis: Associated with thrombophilic mutations?

Abstract

Intravascular coagulation is considered a major pathogenetic mechanism for nontraumatic osteonecrosis. The aim of our study was to evaluate the association of thrombophilic factor V G1691A mutation (factor V Leiden) and G20210A prothrombin mutation with the disease. Mutation presence was investigated by polymerase chain reaction techniques in a study population of 72 adult Caucasian patients with osteonecrosis of the femoral head and 300 healthy Caucasian control subjects. The disease was considered idiopathic in 23 patients and secondary in 49. The factor V Leiden mutation was present in 18% of patients, compared with 4.6% of control subjects, resulting in a statistically significant odds ratio of 4.5. The prothrombin mutation was not significantly increased in the idiopathic osteonecrosis subgroup (8.7% versus 2.6%) with an odds ratio of 3.5. Overall, either of these coagulation disorders was present in 22.2% of patients and in 7.3% of control subjects resulting in a significant odds ratio of 3.6. Factor V Leiden, a genetic risk factor for venous thrombosis, is associated with nontraumatic osteonecrosis of the femoral head, supporting the hypothesis that intravascular coagulation disease.