Homocysteine and bone loss in epilepsy

Seizure. 2007 Jan;16(1):22-34. doi: 10.1016/j.seizure.2006.10.001. Epub 2006 Nov 15.


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.

MeSH terms

  • Absorptiometry, Photon
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Anticonvulsants / adverse effects*
  • Anticonvulsants / pharmacology
  • Blood Urea Nitrogen
  • Bone Density / drug effects*
  • Bone Diseases, Metabolic / diagnostic imaging
  • Bone Diseases, Metabolic / etiology
  • Calcium / administration & dosage
  • Calcium / pharmacology
  • Epilepsy / drug therapy*
  • Epilepsy / ethnology
  • Female
  • Folic Acid / blood
  • Hip / diagnostic imaging
  • Homocysteine / blood
  • Homocysteine / drug effects*
  • Humans
  • Male
  • Middle Aged
  • Osteoporosis / chemically induced*
  • Osteoporosis / diagnostic imaging
  • Regression Analysis
  • Spine / diagnostic imaging


  • Anticonvulsants
  • Homocysteine
  • Folic Acid
  • Calcium