PATHOGENESIS/PATHOPHYSIOLOGY

HYPERHOMOCYSTEINEMIA: A POTENTIAL RISK FACTOR FOR MULTIFOCAL OSTEONECROSIS

John Paul Jones, Jr. MD, Sterling West MD, and Charles J. Glueck MD
Diagnostic Osteonecrosis Center & Research Foundation
Post Office Box 735, Kelseyville, CA 95451

Alcohol-associated osteonecrosis (ON) patients may have increased mean corpuscular volumes (MCV) with macrocytic anemia resulting from deficient folic acid, vitamin B6, and/or vitamin B12. They may also potentially have co-existent hyperhomocysteinemia, an independent risk factor for thromboembolic disease. For example, a female experienced multifocal ON affecting her knees, ankles, and feet. Hypofibrmolytic lipoprotein(a) was elevated. She consumed about 440cc of 100% ethanol weekly and had an MCV of 105, GGT of 80, hyperlipemia (with normal PAI-I), and borderline low vitamin B12. Plasma homocysteine was elevated at 15.4.

This condition can also occur in non-alcoholic ON patients. For example, a male developed maxillary and humeral head lesions. Lipoprotein(a) was elevated. Hypofibrinolytic 4G/4G polymorphism of the PAI-I gene was present. Although MCV ,and plasma homocysteine were normal, the methylene tetrahydrofolate reductase (MTHFR) C677T mutation was homozygous. MTHFR and other major thrombophilic and hypofibrinolytic gene mutations should be measured in these cases.