Epidemiological studies reveal fracture incidence in epilepsy is twice that of the normal population. Much interest has been focused on Vitamin D, however, considering mixed results on non-enzyme inducing anti-epileptic drugs (AEDs) and bone mineral density (BMD) additional metabolic effects may be to blame. AEDs increase serum homocysteine (s-Hcy) by lowering blood folate levels. An association between elevated homocysteine, BMD and increased fracture incidence has been found in non-epilepsy populations. Additionally, folate and Vitamin B12 levels are independently related to bone mineral density in various non-epilepsy populations. This study supports previous research, which found elevated s-Hcy in subjects taking AEDs and that bone loss is related to the use of enzyme-inducing AEDs and changes in alkaline phosphatase. By one-way ANOVA, subjects on phenytoin monotherapy had significantly higher levels of s-Hcy than those on other AEDs (F=5.89, p=.016). Regression analyses revealed homocysteine, fracture history, length of years on AEDs, ethnicity were predictors of spine T scores. Weight and BMI were predictors of both BMD and DEXA T scores. Use of enzyme-inducing AEDs was a negative predictor of spine BMD and T scores, while phenytoin monotherapy was a positive predictor of spine BMD. Lamotrigine was found to be a negative predictor of spine T score. Ambulatory status, menopause and alcohol consumption were predictors of BMD but not T scores. In this study, persons with epilepsy who take nutritional supplementation have 25% lower s-Hcy levels than those who do not. Supplementation continues to be important in preventative epilepsy care.