Effect of antiepileptic drugs on bone density in ambulatory patients

Farhat, Ghada N.; Yamout, Bassem; Mikati, Mohamad A.; Demirjian, Sevag; Sawaya, Raja; Fuleihan, Ghada El‐Hajj

doi:10.1212/wnl.58.9.1348

Cited by 323 publications

(226 citation statements)

References 33 publications

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“…According to WHO criteria, 63, 5% of the patients had a diagnosis of osteopenia / osteoporosis in at least one of the sites measured. This incidence is higher than uncontrolled studies reported in the literature 6,11,12 . Because of the cross-sectional nature of the present study, it was not possible to know if the bone loss is specifically related to the use of AEDs or if there are other reasons for the differences appreciated in this study.…”

Section: Discussioncontrasting

confidence: 55%

“…We have demonstrated significant abnormalities of bone metabolism, characterized by reduced BMD, reduced 25OHD, and increased AP. Previous studies have related these findings to chronic use of AEDs 5,6,11,12 . Serum levels of calcium and PTH were normal and similar to the control group.…”

Section: Discussionmentioning

confidence: 70%

“…The AED in common use are carbamazepine (CBZ), phenytoin (DPH), phenobarbitone (PB), sodium valproate (VPA), primidone (PRM), lamotrigina (LTG) and the benzodiazepines, clobazan (CLB) and clonazepan (CZP). The chronic use of AED can affect bone and mineral metabolism [2][3][4][5][6] . Studies indicate that 20 to 60% of AED users can develop rickets or osteomalacia, especially among older and institutionalized patients.…”

Section: Palavras-chave: Drogas Antiepiléticas Indutoras Hepáticas 2mentioning

confidence: 99%

“…Drugs such as CBZ, PB, PRM and DPH are known to induce hepatic mixed function oxidase activity throughout the microsomal enzymes (P450) in the liver. They are thought to affect bone and mineral metabolism indirectly by increasing the metabolism of vitamin D, thereby causing vitamin D insufficiency or deficiency 2,3,6,10 . The other mechanism of the AEDs involves a direct action on bone cells, increasing bone resorption and formation.…”

Section: Palavras-chave: Drogas Antiepiléticas Indutoras Hepáticas 2mentioning

confidence: 99%

“…In this way, the AED may influence bone turnover 4,5,13 . Both mechanisms can be associated with a reduction in bone mineral density (BMD) 5,6,11,12 . Furthermore, DPH interferes with cation transport in many tissues, directly inhibits intestinal calcium transport and together with PB has been shown to inhibit vitamin D-mediated calcium absorption.…”

Section: Palavras-chave: Drogas Antiepiléticas Indutoras Hepáticas 2mentioning

confidence: 99%

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

Kulak

Borba

Bilezikian

et al. 2004

Arq. Neuro-Psiquiatr.

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-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...

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Section: Discussioncontrasting

confidence: 55%