Bone Status in Patients with Epilepsy: Relationship to Markers of Bone Remodeling

Abstract

Patients with epilepsy and treated with antiepileptic drugs (AEDs) may develop metabolic bone disease; however, the exact pathogenesis of bone loss with AEDs is still unclear. Included were 75 adults with epilepsy (mean age: 31.90 ± 5.62 years; duration of treatment with AEDs: 10.57 ± 3.55 years) and 40 matched healthy controls. Bone mineral content (BMC) and bone mineral densities (BMD) of the femoral neck and lumbar spine were measured using dual-energy X-ray absorptiometry (DEXA). Blood samples were analyzed for calcium, magnesium, phosphate, alkaline phosphatase (ALP), 25-hydroxy vitamin D (25OHD), soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), osteoprotegerin (OPG), and OPG/RANKL ratio (markers of bone remodeling). Compared to controls, patients had lower BMD, BMC, Z-score, and T-score at the femoral neck and lumbar spine (all p < 0.001). Seventy-two percent and 29.33% of patients had osteoporosis of the lumbar spine and femoral neck. Patients had significantly lower serum calcium, 25(OH)D, and OPG and higher ALP, sRANKL levels, and sRANKL/OPG (all p < 0.001). Fifty-two percent of patients had hypocalcemia, 93% had hypovitaminosis D, 31% had high levels of sRANKL, and 49% had low levels of OPG. No differences were identified between DEXA and laboratory results in relation to the type, dose, or serum levels of AEDs. BMD at the femoral neck and lumbar spine were found to be correlated with the duration of illness (p = 0.043; p = 0.010), duration of treatment with AEDs (p < 0.001; p = 0.012), and serum levels of 25(OH)D (p = 0.042; p = 0.010), sRANKLs (p = 0.005; p = 0.01), and OPG (p = 0.006; p = 0.01). In linear regression analysis and after adjusting for gender, age, weight, duration, and number of AEDs, we observed an association between BMD, 25(OH)D (p = 0.04) and sRANKL (p = 0.03) concentrations. We conclude that AEDs may compromise bone health through disturbance of mineral metabolism and acceleration of bone turnover mechanisms.

Vitamin D in epilepsy: vitamin D levels in epilepsy patients, patients on antiepileptic drug polytherapy and drug-resistant epilepsy sufferers

“…We also did not find any In concordance with recent studies, 22,19 drug-resistant seizure patients in our study were not different from their responsive peers with respect to serum 25-OH vitamin D levels. Taken together, the data suggest that the levels of vitamin D in epilepsy patients are a complex product of mechanisms still unclear to present studies.…”

“…18 However, the dose of AED has not been found to correlate with serum 25-OH vitamin D levels. 19 In spite of studies with conflicting data, 20,21 these are some of the factors that can explain the vitamin D deficiency in epilepsy patients.…”

A Cross‐Sectional Study to Assess the Modulation of Wnt Inhibitors following Anti‐Epileptic Drug Therapy and their Correlation with Vitamin D and Receptor Activator of Nuclear Factor κ B Ligand in Indian Women with Epilepsy

“…The inconsistency in the results could be due to the fact that the longer duration of treatment in our study might register changes in the serum RANKL level which may fail to appear in short‐term. Our findings are, however, in agreement with other previous studies showing higher serum RANKL in women treated with AEDs and showing significant positive correlation with duration of treatment . Further, the positive correlation of sclerostin with RANKL observed in our study could be related to the fact that sclerostin regulates RANKL expression in osteocytes while no such reports are available for DKK‐1.…”

Osteoporosis Associated with Epilepsy and the Use of Anti-Epileptics—a Review

“…Recently, genetic variation has been proposed to explain some of the variation in study findings regarding bone disease in epilepsy [65], and where available, this should now be included in studies. In some studies, it has been difficult to conclude whether bone density deficits seen are due to AEMs, or the high rates of vitamin D deficiency in association with, or independent of AEM usage [66,67].…”