title: Bone mass and turnover in women with epilepsy on antiepileptic drug monotherapy.
abstract: Antiepileptic drugs, particularly cytochrome P450 enzyme inducers, are associated with disorders of bone metabolism. We studied premenopausal women with epilepsy receiving antiepileptic drug monotherapy (phenytoin, carbamazepine, valproate, and lamotrigine). Subjects completed exercise and nutrition questionnaires and bone mineral density studies. Serum was analyzed for indices of bone metabolism including calcium, 25-hydroxyvitamin D, parathyroid hormone, insulin growth factor I, insulin binding protein III, and bone formation markers, bone-specific alkaline phosphatase, and osteocalcin. Urine was analyzed for cross-linked N-telopeptide of type I collagen, a bone resorption marker. Calcium concentrations were significantly less in subjects receiving carbamazepine, phenytoin, and valproate than in those receiving lamotrigine (p = 0.008). Insulin growth factor-I was significantly reduced in subjects receiving phenytoin compared with those receiving lamotrigine (p = 0.017). Subjects receiving phenytoin had significantly greater levels of bone-specific alkaline phosphatase (p = 0.007). Our results demonstrate that phenytoin is associated with changes in bone metabolism and increased bone turnover. The lower calcium concentrations in subjects taking carbamazepine or valproate compared with those taking other antiepileptic drugs suggest that these antiepileptic drugs may have long-term effects. Subjects receiving lamotrigine had no significant reductions in calcium or increases in markers of bone turnover, suggesting this agent is less likely to have long-term adverse effects on bone.
authors.affiliation: Department of Neurology, Columbia University, New York, NY 10032, USA. ap390@columbia.edu
authors.forename: Alison M
authors.initials: AM
authors.lastname: Pack
authors.forename: Martha J
authors.initials: MJ
authors.lastname: Morrell
authors.forename: Robert
authors.initials: R
authors.lastname: Marcus
authors.forename: Leah
authors.initials: L
authors.lastname: Holloway
authors.forename: Edith
authors.initials: E
authors.lastname: Flaster
authors.forename: Silvia
authors.initials: S
authors.lastname: Doñe
authors.forename: Alison
authors.initials: A
authors.lastname: Randall
authors.forename: Cairn
authors.initials: C
authors.lastname: Seale
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Shane
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects*; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002220:Carbamazepine / Q000009:adverse effects; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008903:Minerals / Q000378:metabolism; D010672:Phenytoin / Q000009:adverse effects; D017697:Premenopause; D014635:Valproic Acid / Q000009:adverse effects
chemical_list: D000927:Anticonvulsants; D008903:Minerals; D002220:Carbamazepine; D014635:Valproic Acid; D010672:Phenytoin