Incidence of Anticonvulsant Osteomalacia and Effect of Vitamin D: Controlled Therapeutic Trial

Christiansen, Claus; Rødbro, P.; Lund, M.

doi:10.1136/bmj.4.5894.695

Cited by 150 publications

(91 citation statements)

References 17 publications

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“…The coefficient of variability was 0.46% at the lumbar spine and 0.52% at the proximal femur. BMD was expressed as g/cm 2 and as T and Z scores. The World Health Organization (WHO) defines osteoporosis as a T-score < -2.5 and osteopenia as a T-score between -1.0 and -2.49.…”

Section: Methodsmentioning

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%

“…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%

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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: Methodsmentioning

confidence: 99%

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

confidence: 99%

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

confidence: 99%

See 1 more Smart Citation

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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“…However, the most common change in bone metabolism is osteopenia, which may be complicated by fractures (Walloe 1978). A reduced bone mineral content is very often found (Christiansen et al 1973, Hahn et al 1975, Walloe 1978.…”

Section: Discussionmentioning

confidence: 99%

Influence of Diphenylhydantoin on Isotope Release and Bone EnzymesIn Vitro

Pedersen

Lund

Reimann

1982

Acta Orthopaedica Scandinavica

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“…These changes cause radiologic evidence of rickets, and histological evidence of osteomalacia. [1][2][3][4] These patients are also at high risk for pathological fractures due to reduction in the bone mineral density. These EIAED's which include phenytoin, carbamazepine, primidone, phenobarbitone and benzodiazepines cause decrease in bone mineral density by hepatic induction of cytochrome P450 enzymes leading to increased metabolism of vitamin D. 5 LEV was approved as one of the broad spectrum AEDs with good efficacy and safety in various types of epilepsies.…”

Section: Introductionmentioning

confidence: 99%

Levetiracetam monotherapy effect on serum calcium and serum vitamin D in patient of epilepsy

et al. 2017

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INTRODUCTIONIn patients with epilepsy, chronic therapy with conventional enzyme inducing antiepileptic drugs (EIAED's) causes abnormalities in calcium metabolism. These including hypocalcaemia, hypophosphatemia, elevated levels of serum alkaline phosphatase, serum parathyroid hormone and reduced serum levels of biologically active vitamin D metabolites. These changes cause radiologic evidence of rickets, and histological evidence of osteomalacia. [1][2][3][4] These patients are also at high risk for pathological fractures due to reduction in the bone mineral density. These EIAED's which include phenytoin, carbamazepine, primidone, phenobarbitone and benzodiazepines cause decrease in bone mineral density by hepatic induction of cytochrome P450 enzymes ABSTRACT Background: Objective of the study was to determine the Levetiracetam monotherapy effect on serum calcium and serum vitamin D levels in tertiary care hospital in Haryana, India. Methods: A total of 110 patients with epilepsy, were enrolled to the study for one year between April 2013 to August 2014. All male patients aged 15-60 years and premenopausal females with epilepsy were included in the study. The study was a interventional prospective study design. The antiepileptic drug levetiracetam was administered starting from a dose of 20 mg/kg and dose was titrated according to the clinical response. During the follow up period, the subjects were asked about the seizure frequency and other side effects. The patients were be subjected to questionnaires based proforma. Baseline investigations, Hemogram, renal and liver function tests, calcium, phosphate, vitamin D and bone mineral density and T scores were noted. All investigations were repeated after one year of levetiracetam monotherapy. Results: The mean age of onset of seizures in the study group was 23.22±6.62 years. 58% (n=29) were seizure free after 1 year of levetiracetam monotherapy, 28% patients had adequate control and 14% patients had poor control of their seizure episodes. There was an insignificant change in Hemoglobin, total leukocyte count, platelet count, renal parameters and Liver enzymes from baseline over a year of levetiracetam therapy. Serum calcium levels increased insignificantly from baseline levels of 9.68±0.59 mg/dl to 9.72±0.56mg/dl. Vitamin D levels increased from baseline of 39.35±14.91ng/ml to 39.84±14.07 ng/ml. Bone mineral density increased insignificantly from baseline of 0.92±0.13 g/cm 2 to 0.93±0.13 g/cm 2 . Conclusions: Present study has shown an overall beneficial effect on serum calcium, Vitamin D level, bone mineral density and T scores on DEXA scan.

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Incidence of Anticonvulsant Osteomalacia and Effect of Vitamin D: Controlled Therapeutic Trial

Cited by 150 publications

References 17 publications

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

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

Influence of Diphenylhydantoin on Isotope Release and Bone EnzymesIn Vitro

Levetiracetam monotherapy effect on serum calcium and serum vitamin D in patient of epilepsy

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