Decreased Bone Mass and Increased Bone Turnover with Valproate Therapy in Adults with Epilepsy.
Abstract number :
3.117
Submission category :
Year :
2001
Submission ID :
1660
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
S. Ishida, MD, Departments of Neuropsychiatry, Kurume University School of Medicine, Kurume, Fukuoka, Japan; Y. Sato, MD, Departments of Neuropsychiatry, Kurume University School of Medicine, Kurume, Fukuoka, Japan; H. Motooka, MD, Departments of Neuropsy
RATIONALE: Bone loss and hypovitaminosis D are reported in patients taking on antiepileptic drugs, but little is known about changes in bone and calcium metabolism from valproic acid (VPA). We examined the relationship of VPA to bone mass and calcium metabolism in adults with epilepsy treated with received long-term VPA monotherapy, focusing on whether bone mass reduction is accelerated by this drug.
METHODS: Forty adult patients between 20 and 50 years old with epilepsy treated with VPA alone for over 1 year were recruited. Subjects for comparison consisted of two groups: 40 age-matched adults with epilepsy taking PHT as monotherapy for more than 1 year; and 40 community-dwelling age- and gender- matched volunteers serving as healthy controls. Informed consent was obtained from each participant in the presence of a witness. Body weight and body mass index (BMI) were assessed. Using a computer-linked X-ray densitometer (CXD), bone mineral density (BMD) was measured in the second metacarpal of the right hand. Blood samples were analyzed for VPA, PHT, ionized calcium, parathyroid hormone (intact PTH), intact bone Gla protein (BGP; a bone formation marker), pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP; a bone resorption marker), 25-OHD, and 1, 25-[OH]2D. BMD of the second metacarpal was determined as T and Z scores. Serum concentrations of ionized calcium, intact PTH, BGP, ICTP, 25-OHD, and 1, 25-[OH]2D are presented as the mean [plusminus] SD. Unpaired [italic]t[/italic] test were used to assess the significance of differences in continuous variables between VPA and PHT groups.
RESULTS: BMD reduction from control values was 14% (12% in males, 16% in females) with VPA and 13% (12% in males, 15% in females) with PHT. Among VPA patients, 9 (23%) had T-scores below -2.5 SD, suggesting osteoporosis; 15 VPA (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 BGP and ICTP associated with either drug significantly exceeded control values. Z-scores for BMD in 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 treatment causes reduction in BMD in adult patients with epilepsy. Since patients under treatment for epilepsy are at increased risk for osteoporosis, serum concentrations of a bone resorption marker such as ICTP as well as ionized calcium should be measured routinely during long-term VPA therapy.