title: Heterozygosity for the Leiden mutation of the factor V gene, a common pathoetiology for osteonecrosis of the jaw, with thrombophilia augmented by exogenous estrogens.
abstract: We assessed whether heterozygosity for the thrombophilic Leiden mutation of the factor V gene (MFV) was pathogenetic for alveolar osteonecrosis of the jaw and chronic facial pain (neuralgia-inducing cavitational osteonecrosis (NICO)) in 89 patients with NICO. A second specific aim was to assess for thrombophilic synergism between exogenous estrogens and MFV for development of osteonecrosis of the jaw. MFV was found in 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 101 women (chi2 = 14.8, p = 0.001) and 4 (3.7%) of 108 men (chi2 = 20.4, p = 0.001). Patients with and without MFV did not differ in tissue plasminogen activator activity, plasminogen activator inhibitor activity, proteins C and S, lipoprotein (a), or anticardiolipin antibodies (p > 0.05). Use of standard-dose oral contraceptives and/or postmenopausal estrogens before the development of NICO was more common in female patients with MFV (13 (81%) of 16) than in those without it (23 (38%) of 60; chi2 = 9.33, p = 0.002). When the thrombophilic effects of such exogenous estrogens were superimposed on the familial resistance to activated protein C associated with MFV, thrombophilia was augmented 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 identify women at high risk for venous thrombosis and osteonecrosis, in whom use of oral contraceptives or postmenopausal estrogens might be contraindicated, while identifying a much larger group of women (approximately 97%) without the mutation whose risk from exogenous estrogens would be low.
authors.affiliation: Cholesterol Center, Jewish Hospital, Cincinnati, OH 45229, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Glueck
authors.forename: R E
authors.initials: RE
authors.lastname: McMahon
authors.forename: J E
authors.initials: JE
authors.lastname: Bouquot
authors.forename: D
authors.initials: D
authors.lastname: Triplett
authors.forename: R
authors.initials: R
authors.lastname: Gruppo
authors.forename: P
authors.initials: P
authors.lastname: Wang
mesh_terms: D003276:Contraceptives, Oral / Q000009:adverse effects; D017931:DNA Primers / Q000737:chemistry; D004587:Electrophoresis, Agar Gel; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D004967:Estrogens / Q000009:adverse effects*; D005156:Facial Neuralgia; D005165:Factor V / Q000032:analysis / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D007571:Jaw Diseases / Q000209:etiology* / Q000235:genetics; D017270:Lipoprotein(a) / Q000032:analysis; D008297:Male; D009154:Mutation; D010020:Osteonecrosis / Q000209:etiology* / Q000235:genetics; D011486:Protein C / Q000032:analysis; D017293:Protein S / Q000032:analysis; D019851:Thrombophilia / Q000150:complications / Q000235:genetics*; D010959:Tissue Plasminogen Activator / Q000032:analysis / Q000037:antagonists & inhibitors
chemical_list: D003276:Contraceptives, Oral; D017931:DNA Primers; D004967:Estrogens; D017270:Lipoprotein(a); D011486:Protein C; D017293:Protein S; C095381:factor V Leiden; D005165:Factor V; D010959:Tissue Plasminogen Activator