HETEROZYGOSITY FOR THE LEIDEN MUTATION OF THE FACTOR-V GENE, A COMMONPATHOETIOLOGY FOR OSTEONECROSIS OF THE JAW, WITH THROMBOPHILIA AUGMENTED BY EXOGENOUS ESTROGENS

We assessed whether heterozygosity for the thrombophilic Leiden mutati on of the factor V gene (MFV) was pathogenetic for alveolar osteonecro sis of the jaw and chronic facial pain (neuralgia-inducing cavitationa l osteonecrosis (NICO)) in 89 patients with NICO. A second specific ai m was to assess for thrombophilic synergism between exogenous estrogen s and MFV for development of osteonecrosis of the jaw. MFV was found i n 24% of the patients, 16 (21%) of 76 women and 5 (39%) of 13 men. The mutation was much less common in healthy normal controls: 3 (3%) of 1 01 women (chi(2) = 14.8, p = 0.001) and 4 (3.7%) of 108 men (chi(2) = 20.4, p = 0.001). Patients with and without MFV did not differ in tiss ue plasminogen activator activity, plasminogen activator inhibitor act ivity, proteins C and S, lipoprotein (a), or anticardiolipin antibodie s (p > 0.05). Use of standard-dose oral contraceptives and/or postmeno pausal estrogens before the development of NICO was more common in fem ale patients with MFV (13 (81%) of 16) than in those without it (23 (3 8%) of 60; chi(2) = 9.33, p = 0.002). When the thrombophilic effects o f such exogenous estrogens were superimposed on the familial resistanc e to activated protein C associated with MFV, thrombophilia was augmen ted and the risk of osteonecrosis was increased. Since heterozygosity for this mutation occurs in at least 3% of unselected, healthy women, measurement of resistance to activated protein C and MFV would Identif y women at high risk for venous thrombosis and osteonecrosis, in whom use of oral contraceptives or postmenopausal estrogens might be contra indicated, while identifying a much larger group of women (approximate ly 97%) without the mutation whose risk from exogenous estrogens would be low.