Suplementación con vitamina D en epilepsiaestudio en pacientes con antiepilépticos clásicos y de nueva generación

Abstract

INTRODUCTION AND PURPOSE: Bone metabolism is a complex system where numerous actors are involved, including vitamin D. Classical antiepileptic drugs (AED) as carbamazepine (CBZ), phenytoin (PHT) and valproic acid (VPA) are strongly related to disturbances in bone metabolism in persons with epilepsy, and can lead to a premature osteoporosis. Vitamin D supplementation has been recommended but dosage, and even type of supplementation, are still not clear. Moreover, we don&apos;t know if newer AEDs have an impact on bone, though, the aim of this study was to determine if newer AEDs are related to bone metabolism impairment, compared to classical AEDs, in terms of densitometric and biochemical parameters, and if vitamin D administration as performed in everyday clinical practice is related to a better outcome on densitometry or biochemical parameters in patients on chronic AEDs. METHODS: a prospective observational study was conducted on adult epileptic outpatients from the Epilepsy Unit of Arrixaca&apos;s Hospital (Murcia), on stable monotherapy with AEDs, either classical (CBZ, PHT or VPA) or new (levetiracetam (LEV), eslicarbazepine (ESL), lacosamide (LCM)), that were going to start vitamin D supplementation. A similar sample of patients not taking vitamin D was collected as control group. Clinical data, level of exercise, skin phototype, nutritional status and general biochemical parameters were collected. Bone mineral density (BMD) at lumbar level and neck of left femur was studied by dual energy X-ray absorptiometry at the beginning of the study and after 6 months, as well as vitamin D levels and bone remodeling biomarkers. Polymorphisms of genes related to bone metabolism were determined at baseline. RESULTS: 27 patients on vitamin D supplementation (400 UI cholecalciferol and 1500 mg calcium carbonate) and 37 controls were studied. There was no difference between the two groups (vitD and control group), in terms of clinical characteristics and general biochemical parameters, excepting for smokers that were more frequent in the control group. Glycemia was found to be a confounding factor, which was controlled in statistical analysis. ESR1P-PVU polymorphism was independently related to changes in femoral z/t score (p _ 0,046) and with vitamin D supplementation (p = 0,031). Patients treated with neutral AEDs (LEV and LCM) had similar vitamin D levels as patients on enzyme-inducers (CBZ, PHT or ESL) and inhibitors (VPA): 20,10 ± 9,92 vs 15,65 ± 6,56 vs 21,30 ± 8,12 ng/ml, respectively. Baseline osteocalcin levels were higher in pacients on LEV compared to VPA (p = 0,044). Lumbar BMD was higher in patients on neutral AEDs compared to inducers (1,106 ± 0,15 vs 0,970 ± 0,14 g/m2, p = 0,025). In the supplemented group, the number of patients with vitamin D sufficiency increased from 3 to 7 (12 to 28%), insufficient patients grew from 44 to 56% and deficient patients decreased from 11 to 4, (p = 0,019). Bone remodeling biomarkers, both formation and resorption markers, decreased significantly in patients with vitamin D levels < 30 ng/ml, while resorption markers increased in patients in control group. Lumbar BMD and z/t score increased significantly in supplemented patients, compared to controls (0,027 ± 0,047 g/m2 vs -0,003 ± 0,064 g/m2, p = 0,025), and femoral BMD and z/t score also increased but did not reach statistical significance. Vitamin D levels or densitometric parameters were not influenced by AED type. CONCLUSIONS: LEV was not associated to BMD changes in this study, but it was related to low vitamin D levels, as were enzyme-inducer AEDs. Moreover, a tendency to a decrease in bone formation after six months was detected, not depending on vitamin D and calcium supplementation. Administratio of 400 IU of vitamin D and 1500 mg of calcium carbonate was associated to an increase of femoral and lumbar densitometric parameters, reaching statistical significance for femoral z/t score, and AED did not show any influence on it. Normalization of vitamin D levels was not reached with this dosage of supplementation, thus an individualized higher dose could be recommended. In addition, patients that were insufficient or deficient at baseline showed a more evident improvement in the studied patterns. Presence of "p" allele of ESR1P-PVU polymorphism was related to an improvement of femoral z/t-score in supplemented patients.