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.
Highlights
Epilepsy is one of the most common neurological disorders [1] and its treatment is life-long in nearly one-third of the patients [2]
AIM OF THE WORK This study was aimed to determine the followings in adult patients with epilepsy and on chronic treatment with antiepileptic drugs (AEDs) [1] the types and severity of bone disease, [2] the potential mechanism(s) of osteoporosis/osteopenia induced by AEDs as data on this subject are controversial and inconsistent, and [3] the status of OPG/receptor activator of nuclear factor-kappa B ligands (RANKL) system and its relationship to Bone mineral density (BMD) and related biochemical parameters of bone disease
The results of this study showed that in ambulatory adults with epilepsy and on chronic treatment with AEDs, there is an increased risk of [1] bone loss and fracture, [2] hypocalcemia (52%) and 25(OH)D deficiency/insufficiency, [3] increased bone turnover as indicated by lower serum levels of OPG and higher levels of sRANKL and sRANKL/OPG ratio, and [4] metabolic bone compromise with prolongation of the duration of treatment with AEDs due to disturbed mineral metabolism associated with compromise of bone remodeling with accelerated bone turnover
Summary
Epilepsy is one of the most common neurological disorders [1] and its treatment is life-long in nearly one-third of the patients [2]. Several large epidemiological studies indicated that patients with epilepsy are at two- to six-folds increase in the risk of fractures compared to the general population [3]. Reports suggested that institutionalization, inadequate dietary intake with vitamin D deficiency/insufficiency, reduced sunlight exposure [5], physical inactivity [6], aging [7], and female sex [8] are risk factors for osteopathy with epilepsy. Reports incriminated AEDs with enzyme induction activity or their metabolism through hepatic cytochrome P450 enzyme system, as causes of metabolic bone disease due to increasing metabolism of vitamin D with secondary hypocalcemia and hyperparathyroidism [13,14,15]. Several studies reported that both enzyme inducing and non-enzyme inducing AEDs are potentially implicated for the comorbid metabolic bone disease [10, 12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
