Bone mineral density and serum levels of 25 OH vitamin D in chronic users of antiepileptic drugs

Abstract

-The aim of this cross sectional study was to evaluate bone mineral density (BMD) and serum levels of 25-hydroxy vitamin D (25OHD) in a group of patients taking antiepileptic drugs (AED) for a seizure disorder. Between May-2001 and January-2003, we evaluated 58 patients (40 women/18 men), 34.4+6 years old living in Curitiba or in its metropolitan area, on antiepileptic therapy for 2 to 38 years (10 on monotherapy /48 on multiple drugs regime). The group was matched by age, gender, and bone mass index to 29 healthy subjects (20 women/ 9 men); 34.2+5.9 years old. Medical history and physical exam were performed on all subjects with particular information sought about fractures and risks factors for osteoporosis. Blood samples were collected for total serum calcium, albumin, phosphorus, creatinine, total alkaline phosphatase, and liver function tests. BMD of the lumbar spine, femur and forearm was determined by dual energy X-ray absorptiometry (DXA, Hologic QDR 1000). Between February and April-2003, other blood samples were collected to measure 25OHD, intact paratohormone (PTH) and calcium. Unemployment and smoking history were more frequent among patients than among controls (p<0.05). Fifteen patients had a fracture history, all of which occurred during a seizure. The BMD of the lumbar spine (0.975+0. 13 g/cm 2 vs. 1.058+0.1 g/cm 2 ; p<0.03) and of the total femur (0.930+0.1 g/cm 2 vs. 0.988+0.12 g/cm 2 ; p<0.02) was lower in patients than in controls. In 63.5% of patients and in 24.1 % of controls a T-score < -1.0 in at least one site was seen. The AED users had higher total alkaline phosphatase and lower 25OHD (p<0.02). No correlations between BMD and 25OHD were found. The use of phenytoin was correlated with a greater incidence of fractures (RR: 2.38). We conclude that patients on chronic use of AED have alterations in bone metabolism characterized in this study by lower BMD of the lumbar spine and total femur and lower serum concentrations of 25OHD.KEY WORDS: Enzyme-inducing antiepileptic drugs, 25OH vitamin D, osteomalacia. Densidade mineral óssea e níveis séricos de 25 OH vitamina D em usuários crônicos de drogas antiepilépticasRESUMO -O objetivo deste estudo transversal foi avaliar a densidade mineral óssea (DMO) e os níveis de 25hidroxi vitamina D (25OHD) em um grupo de pacientes com epilepsia e usuários crônicos de drogas antiepilépticas (DAE). Entre maio-2001 e janeiro-2003 avaliamos 58 pacientes (40 mulheres/18 homens) residentes em Curitiba ou região metropolitana da cidade, com média de idade 34,4+6 anos e tempo de tratamento entre 2 e 38 anos (10 em monoterapia/48 em politerapia). O grupo de pacientes foi emparelhado por idade, sexo e índice de massa corpórea com 29 indivíduos aparentemente sadios (20 mulheres/9 homens; 34,2+5,9 anos). Pacientes e controles foram submetidos a anamnese e exame clínico, com ênfase na história de fraturas e fatores de risco para osteoporose. Nas visitas foram coletadas amostras de sangue para dosagens de cálcio, albumina, fósforo, creatinina, fosfatase alcalin...

Vitamin D status and health correlates among German adults

“…For this purpose, we excluded participants with antiepileptic therapy (n¼31) to make sure that the observed association was not biased by this prevailing treatment. Antiepileptic drugs are inducers of the cytochrome P450 system in the liver, promoting the metabolism of 25OHD to less biologically active analogs (Kulak et al, 2004;Mintzer et al, 2006). We calculated prevalence rates across sex-specific quartiles of serum 25OHD levels to examine the association between serum 25OHD levels and hypertension as well as a lifetime diagnosis of diabetes mellitus and cardiovascular disease.…”

Primary hypoparathyroidism presenting as refractory status epilepticus

“…When status epilepticus (SE) is refractory to first and second line anticonvulsants, the condition becomes critical 5 For treatment of these patients, non-enzyme-inducing anticonvulsants are preferred. So far the knowledge goes; lamotrigine does not have any effect on calcium and bone dynamics.…”

Efeitos endócrinos e metabólicos das drogas antiepilépticas

“…observaram redução na DMO em coluna lombar e fêmur proximal em 59% de crianças e adultos usuários crônicos de DAE (12). Similarmente, num estudo realizado na nossa instituição, também foi verificado que usuários crônicos de DAE apresentam menor DMO e níveis de 25-OH-D mais baixos em comparação a controles pareados por sexo, idade e índice de massa corporal (IMC) (13). Na presente casuística, pacientes que utilizaram fenobarbital tiveram DMO significativamente menor do que aqueles que nunca haviam sido expostos a essa droga, além de apresentarem níveis mais elevados de telopeptídeo carboxiterminal do colágeno tipo I (CTX-I), um marcador de reabsorção óssea (13,14).…”

“…Similarmente, num estudo realizado na nossa instituição, também foi verificado que usuários crônicos de DAE apresentam menor DMO e níveis de 25-OH-D mais baixos em comparação a controles pareados por sexo, idade e índice de massa corporal (IMC) (13). Na presente casuística, pacientes que utilizaram fenobarbital tiveram DMO significativamente menor do que aqueles que nunca haviam sido expostos a essa droga, além de apresentarem níveis mais elevados de telopeptídeo carboxiterminal do colágeno tipo I (CTX-I), um marcador de reabsorção óssea (13,14). Em estudos histomorfométricos, a principal alteração encontrada é uma alta taxa de remodelação, sem mudanças significativas na mineralização óssea (11).…”