STUDY DESIGN:
Thrombophilia was treated with
Coumadin (DuPont) in 10 patients; hypofibrinolysis was treated with
Winstrol (
Sanofi-Winthrop) in 20 patients, including 4 who had mixed
thrombophilia and hypofibrinolysis and had previously been treated with
Coumadin. The initial treatment period was targeted to be 4 months. Each patient was asked to keep a daily written
pain-relief numeric rating score and side-effects diary and to provide a summary
pain-relief numeric rating score and side effects compilation for the total treatment period.
RESULTS: There were 4 men and 22 women in the study group; their mean age was 49 +/- 11 years. The mean onset of their
osteonecrosis pain was at age 45 +/- 12 years, and the mean duration of their
facial pain prior to
therapy was 4.5 +/- 4.2 years. Ten patients had one or more thrombophilic traits (there were two patients with
protein C deficiency, five with resistance to activated
protein C and/or the mutant
Factor V Leiden gene, and four with high
anticardiolipin antibodies). The 10 patients who were thrombophilic were treated with
Coumadin (the international normalized ratio was targeted to 2.5-3.0) for 22 +/- 9 weeks. By self-reported
pain-relief numeric rating scores, 6 of the 10 patients with
thrombophilia (60%) had > or = 40%
pain relief, 2 (20%) had no change, and 2 (20%) had increased
pain (30% and 80% worse). Nine of the 10 patients with
thrombophilia (90%) had no
Coumadin-related side effects; 1 patient (10%) stopped
Coumadin therapy (after 28 weeks) because of
nosebleeds.
Winstrol (6 mg per day) was used for 16 +/- 9 weeks in 20 patients with hypofibrinolysis, some of whom had one or more hypofibrinolytic traits (10 had high levels of
plasminogen activator/inhibitor activity, usually accompanied by low stimulated
tissue plasminogen activator activity; 13 had high Lp[a]
lipoprotein). Of these 20 patients with hypofibrinolysis, 9 patients (45%) had > or = 40%
pain relief, 3 patients (15%) had 20% to 30% relief, 5 patients (25%) had no improvement, and 3 patients (15%) had increased
pain (30% worse, 60% worse, and 70% worse). Six of the 20 patients with hypofibrinolysis (30%) had no
Winstrol-related side effects, while 14 (70%) had side effects that could be attributed to
Winstrol, including
weight gain, peripheral
edema, increased facial and body hair, and
acne--all of which were reversed within 6 weeks of stopping
Winstrol therapy.
CONCLUSIONS: We postulate that
thrombophilia and hypofibrinolysis lead to impaired venous circulation and venous
hypertension of the mandible/maxilla with subsequent development of
osteonecrosis and chronic
facial pain. In many patients,
facial pain can be ameliorated by treating the pathogenetic coagulation defects with
Coumadin or
Winstrol. Large, double-blind, placebo-controlled crossover studies will be required in the future to validate these preliminary results and to determine whether
pain relief with
Coumadin or
Winstrol justifies the risks and side effects associated with these medications, especially for long-term use, in
osteonecrosis of the jaws.