Effect of carbamazepine and valproate on bone mineral density

Sheth, Raj D.; Wesolowski, Carl A.; Jacob, Jayanthi; Penney, Sharon; Hobbs, Gerald R.; Riggs, Jack E.; Bodensteiner, John B.

doi:10.1016/s0022-3476(95)70304-7

Cited by 267 publications

(197 citation statements)

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“…A study on adolescents with uncomplicated idiopathic epilepsy found a low areal bone mineral density (BMD) in patients who received monotherapy with VPA but not in patients receiving CBZ. 6 However, other authors reported that areal BMD was normal in such patients 7 or that areal BMD was decreased in girls but not in boys. 8 These studies were limited to the analysis of areal BMD (g/cm 2 ), a measure integrating both bone size and 3-dimensional ("volumetric") BMD (vBMD).…”

mentioning

confidence: 97%

Analysis of the Musculoskeletal System in Children and Adolescents Receiving Anticonvulsant Monotherapy With Valproic Acid or Carbamazepine

et al. 2001

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ABSTRACT. Objective. To examine bone development in children and adolescents who have uncomplicated idiopathic epilepsy and had received monotherapy with carbamazepine or valproic acid for at least 1 year.Methods. Thirty-nine patients from 6 to 19 years of age (18 girls) were studied. Total bone mineral content (BMC) and trabecular volumetric bone mineral density were measured at the distal radius using peripheral quantitative computed tomography. Maximum isometric grip force was determined with a standard dynamometer. Alkaline phosphatase activity and deoxypyridinoline (a marker of bone resorption) were assessed in serum and urine, respectively.Results. Trabecular volumetric bone mineral density was significantly decreased in the entire group (z score mean ؎ standard deviation: ؊0.62 ؎ 1.04) and in the subgroup using valproic acid (؊0.75 ؎ 1.18). In the carbamazepine subgroup, there was a similar but nonsignificant trend (؊0.50 ؎ 0.90). Total BMC and isometric maximum grip force were normal in the entire study population (0.10 ؎ 1.22) and in the 2 subgroups. The relationship between BMC and grip force was similar between patients and healthy participants. Urinary levels of deoxypyridinoline were significantly elevated above normal in the whole study population (1.35 ؎ 2.00) and in both the valproic acid and the carbamazepine subgroups.Conclusion. Bone turnover can be increased, but bone mass is adequate in children and adolescents who have uncomplicated idiopathic epilepsy and who receive monotherapy with carbamazepine or valproic acid. Pediatrics 2001;108(6). URL: http://www.pediatrics.org/ cgi/content/full/108/6/e107; anticonvulsant, bone density, bone mass, bone metabolism, muscle.ABBREVIATIONS. CBZ, carbamazepine; VPA, valproic acid; BMD, bone mineral density; vBMD, volumetric bone mineral density; pQCT, peripheral quantitative computed tomography; BMC, bone mineral content; SD, standard deviation.

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confidence: 97%

Analysis of the Musculoskeletal System in Children and Adolescents Receiving Anticonvulsant Monotherapy With Valproic Acid or Carbamazepine

et al. 2001

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“…Valproate monotherapy was first reported to reduce BMD in children. 5 Since then, most studies have failed to demonstrate low bone mass, 2,6,7 but, as many studies using dual-energy X-ray absorptiometry (DXA) failed to apply the necessary size corrections, this issue remains unresolved. Similarly, a certain degree of vitamin D insufficiency (as defined by 25OHD between 25 and 80nmol ⁄ l [10-32ng ⁄ ml]), as well as alterations in bone turnover, have been observed in some, but not all, studies.…”

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confidence: 99%

Chronic antiepileptic monotherapy, bone metabolism, and body composition in non‐institutionalized children

Rauchenzauner

Griesmacher

Tatarczyk

et al. 2010

Develop Med Child Neuro

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AIM The aim of this study was to determine the influence of chronic monotherapy with antiepileptic drugs (AEDs) on vitamin D levels, bone metabolism, and body composition.METHOD Eighty-five children (38 males, 47 females; mean age 12y 5mo, SD 3y 4mo) were treated with valproate and 40 children (28 males, 12 females; mean age 11y 10mo, SD 3y) were treated with other AEDs (lamotrigine, sulthiame, or oxcarbazepine), comprising the non-valproate group. Forty-one healthy children (29 males 12 females; mean age 12y 1mo, SD 3y 5mo) served as a comparison group. Height, weight, body impedance analysis, 25-hydroxyvitamin D, calcium, phosphate, two bone resorption markers (receptor activator of nuclear factor jB ligand [RANKL] and tartrate-resistant acid phosphatase 5b [TRAP5b]), osteoprotegerin, and leptin were measured. RESULTS No child was vitamin D deficient as defined by a 25-hydroxyvitamin D (25OHD) level ofless than 25nmol ⁄ l (<10ng ⁄ ml). Leptin, body fat, weight standard deviation score (SDS), and body mass index (BMI) SDS were all significantly higher (each p<0.001) in valproate-treated children than in the non-valproate group, as were calcium (p=0.027) and RANKL (p=0.007) concentrations. Similarly, leptin was significantly higher in the valproate group than in control participants (p<0.001), as were body fat (p=0.023), weight SDS (p=0.046), BMI SDS (p=0.047), calcium (p<0.001), and RANKL (p<0.001), whereas TRAP5b concentrations were significantly lower in the valproate-treated group (p=0.002). Furthermore, calcium and RANKL levels were significantly higher in the non-valproate group than in comparison participants (p<0.001 and p=0.016 respectively).INTERPRETATION Non-enzyme-inducing or minimal enzyme-inducing AED monotherapy does not cause vitamin D deficiency in otherwise healthy children with epilepsy. Valproate therapy is associated with increases in weight, body fat, and leptin concentration, as well as with a bone metabolic profile that resembles slightly increased parathyroid hormone action.Chronic antiepileptic drug (AED) therapy has been associated with vitamin D deficiency, low bone mass, increased fracture risk, and altered bone turnover.1 The underlying pathophysiological mechanisms are poorly understood but are probably multifactorial. Most older AEDs (e.g. phenobarbital, phenytoin, and carbamazepine) are strong cytochrome P450 (CYP450) enzyme inducers, thereby causing altered steroid and vitamin D metabolism, whereas valproic acid (valproate) and the newer AEDs such as lamotrigine and oxcarbazepine are non-enzyme inducers or minimal enzyme inducers. Some, but not all, studies in adults treated with new AEDs have observed vitamin D deficiency (as defined by a 25-hydroxyvitamin D [25OHD] level <25nmol ⁄ l [<10ng ⁄ ml]) and low bone mineral density (BMD).2-4 Studies on the effect of chronic AED therapy on bone metabolism in children have produced conflicting results. Valproate monotherapy was first reported to reduce BMD in children. 5 Since then, most studies have failed to demonstrate low bone ma...

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“…Although this is still considered an important mechanism, later studies have shown that AEDs may cause bone loss even in the absence of vitamin D deficiency (Farhat et al, 2002;Andress et al, 2002). Furthermore, valproate, a CYP450 inhibitor, has also been shown to have an adverse effect on bone health, probably via completely different mechanisms (Sheth et al, 1995;Sato et al, 2001;Guo et al, 2001;. Decreased intestinal absorption of calcium, resistance to parathyroid hormone, calcitonin deficiency, interference with vitamin K metabolism, and a direct drug-effect on bone cell functions have also been suggested as possible mechanisms (Feldkamp et al, 2000;Petty et al, 2007).…”

Section: Effects On Bone Metabolismmentioning

confidence: 99%

Adverse Metabolic Effects of Antiepileptic Drug Treatment

Nakken¹

2011

Novel Treatment of Epilepsy

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Effect of carbamazepine and valproate on bone mineral density

Cited by 267 publications

References 23 publications

Analysis of the Musculoskeletal System in Children and Adolescents Receiving Anticonvulsant Monotherapy With Valproic Acid or Carbamazepine

Analysis of the Musculoskeletal System in Children and Adolescents Receiving Anticonvulsant Monotherapy With Valproic Acid or Carbamazepine

Chronic antiepileptic monotherapy, bone metabolism, and body composition in non‐institutionalized children

Adverse Metabolic Effects of Antiepileptic Drug Treatment

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