title: Decreased bone mass and increased bone turnover with valproate therapy in adults with epilepsy.
abstract: BACKGROUND
  Bone loss and hypovitaminosis D are reported in patients taking antiepileptic drugs, but little is known about changes in bone and calcium metabolism from valproic acid (VPA).
  
  
  OBJECTIVE
  To assess the relationship of VPA to bone mass and calcium metabolism in 40 adults with epilepsy on long-term VPA monotherapy, 40 age- and sex-matched epileptic patients taking phenytoin (PHT), and 40 healthy control subjects. Bone mineral density (BMD) of the second metacarpal was determined as T- and Z-scores.
  
  
  RESULTS
  BMD reduction from control values was 14% (12% in men, 16% in women) with VPA and 13% (12% in men, 15% in women) with PHT. Among patients on VPA, nine (23%) had T-scores below -2.5 SD, suggesting osteoporosis; 15 (37%) had T-scores between -1 and -2.5 SD, suggesting osteopenia. Serum concentrations of calcium were significantly higher with VPA than in PHT or control groups. Serum concentrations of bone Gla protein (a bone formation marker) and pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP; a bone resorption marker) associated with either drug significantly exceeded control values. Z-scores for BMD in the VPA group correlated negatively with calcium and ICTP. High ICTP correlated positively with ionized calcium, implying that increased bone resorption caused the latter.
  
  
  CONCLUSIONS
  Long-term VPA monotherapy can increase bone resorption, leading to decreased BMD.
authors.affiliation: Department of Internal Medicine, Kurume University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sato
authors.forename: I
authors.initials: I
authors.lastname: Kondo
authors.forename: S
authors.initials: S
authors.lastname: Ishida
authors.forename: H
authors.initials: H
authors.lastname: Motooka
authors.forename: K
authors.initials: K
authors.lastname: Takayama
authors.forename: Y
authors.initials: Y
authors.lastname: Tomita
authors.forename: H
authors.initials: H
authors.lastname: Maeda
authors.forename: K
authors.initials: K
authors.lastname: Satoh
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology*; D001842:Bone and Bones / Q000187:drug effects* / Q000503:physiopathology*; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D014635:Valproic Acid / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid