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Aim Patients with epilepsy frequently develop hyponatremia due to the treatment with antiepileptic drugs and have an increased risk of developing metabolic bone disease. Hyponatremia is known to be associated with osteoporosis. The aim of the study was to investigate the association between hyponatremia and osteoporosis in patients with epilepsy. Method and material This cross-sectional study included patients with epilepsy from a tertiary epilepsy out-patient clinic in Denmark, who had a Dual Energy X-ray Absorptiometry scan performed and an accompanying plasma sodium (p-Na) measured prior to or a maximum of 14 days after the scan. Information regarding the patients' health and medical conditions were obtained from their medical reports. Results A total of 695 patients (females 53.8%, age 49 (34:63) years (median (quartiles)) were included. 10.4% had hyponatremia (p-Na ≤ 135 mmol/L). The hyponatremic patients had significantly lower T-scores in the lumbar spine, femoral neck and total femur (all p Conclusion We conclude that hyponatremia is common in patients with epilepsy and that moderate and severe hyponatremia is independently associated with decreased bone mineral density in the lumbar spine. Therefore, hyponatremia in a patient with epilepsy should warrant further examination of the patient for bone loss and osteoporosis.

Background: Osteoporosis is a bone disorder defined by a decrease in bone mineral density (BMD) which can lead to an increased risk of fractures. Patients with epilepsy are more prone to having fractures. When accounting for seizure-related fractures, the epilepsy patient population still suffers from an increased risk of fractures. This can be attributed to adverse effects of antiepileptic drugs (AEDs). Aim: The aim of this study was to investigate the association between the use of AEDs and decreased BMD in a large unselected population of Danish patients with epilepsy. Method: The study was a cross-sectional study based on data retrieved from 835 patients visiting an outpatient Epilepsy Clinic in Glostrup, Denmark, from January 1st 2006 - January 31st 2018. The data included results from DXA-scans and demographic information. Logistic regression models and other statistical analyses were performed. Results: The results showed that the odds for having osteoporosis when taking EIAEDs were 2.2 (95 % CI: 1.2–3.8, P = 0.007) times higher than those taking NEIAEDs. Furthermore, the odds for having osteoporosis increased with duration of epilepsy (OR = 1.0, 95 % CI: 1.0 – 1.0, P = 0.001) and when the patients consume two AEDs compared to one AED (OR = 2.3, 95 % CI: 1.3–4.1, P < 0.001). Additionally, consuming three AEDs compared to one lead to a 2.3 times higher risk of having osteoporosis (95 % CI: 1.2–4.4, P = 0.01). Conclusion: When accounted for many riskfactors, EIAEDs, polytherapy with AEDs and duration of epilepsy are correlated with osteoporosis. There is a need for using these known riskfactors as guidelines in indentifying patients at increased risk of developing osteoporosis.

Background: Metabolic bone disease and fractures are a great problem for patients with epilepsy. The use of antiepileptic drugs (AEDs) is known to play an essential role in the progression of bone loss by various pathophysiological mechanisms. The aim of this study was to evaluate the effects of AEDs on bone microstructure as an additional cause of an increased fracture risk in patients with epilepsy. Methods: Five groups of each of 12 female rats were orally dosed daily for 8 weeks with either carbamazepine (CBZ) (60 mg/kg), eslicarbazepine (ESL) (80 mg/kg), valproic acid (VPA) (300 mg/kg), levetiracetam (LEV) (50 mg/kg) or saline (control (CTL)). Following killing, dissected femurs were analyzed using X-ray micro-computed tomography (µCT), dual-energy X-ray absorptiometry (DXA) and biomechanical testing. In addition, serum bone turnover markers (BTM) were monitored throughout the experiment. Results: Compared to CTL treatment, VPA decreased bone volume fraction by 19%, decreased apparent density by 14% and increased structural model index by 41%. No changes were observed in bone biomechanics nor mineral density evaluated by DXA or in levels of BTM. Conclusions: Our findings suggest that VPA affects the microarchitectural properties of the bone. The AEDs CBZ, ESL and LEV appear to have less adverse effects on bone biology and may be a better choice when treating patients with respect to bone health.

Bone formation markers bone-specific alkaline phosphatase and osteocalcin are used in many clinical situations. Therefore, we calculated reference intervals for the two markers and investigated how they are influenced by several factors including sex and age. Furthermore, we established clinically relevant reference intervals for the two markers. The bone turnover markers (BTMs), bone-specific alkaline phosphatase (bone ALP), and osteocalcin (OC), are frequently measured formation markers. The purpose of this study was to establish reference intervals (RIs) for the two BTMs in a general adult Danish population. Bone ALP and OC were measured on the iSYS (IDS Plc) automatic analyzer in samples from the Danish Health2006 5-year follow-up study on serum from 2308 participants (54% women, age range 24–76). Participants with self-reported diagnosis of osteoporosis or receiving hormonal replacement were excluded from analyses while participants on hormonal contraceptives were included. The geometric mean and 95%RI for bone ALP were 13.9 μg/L (7.6–25.6) for men and 13.8 μg/L (7.0–27.4) for women, while for OC 16.0 μg/L (7.5–34.4) for men and 18.6 μg/L (8.1–42.9) for women. Levels of bone ALP increased with increasing age (β 1.004, p

Hyponatremia [p[Na], Highlights • Patients with epilepsy and hyponatremia have low bone turnover. • Defining chronic hyponatremia in patients with epilepsy is challenging. • Bone turnover markers are not affected by salt supplements.

Purpose Patients with epilepsy have a greatly increased risk of osteoporosis and fractures. The literature is diverse and contradictory when dealing with the underlying pathophysiological mechanisms. Consequently, the purpose of this review was to shed light on the multifactorial causes behind the increased occurrence of metabolic bone disease in patients with epilepsy and to identify areas for future research. Methods A review of the literature was performed searching PubMed with relevant Medical Subject Headings MeSH terms. The results of the search were evaluated for relevance to the review based on the title and abstract of the publication. Publications in language other than English and publications pertaining only pediatric patients were excluded. For all studies, included reference lists were evaluated for further relevant publications. In total, 96 publications were included in this explorative review. Results The high occurrence of metabolic bone disease in patients with epilepsy is multifactorial. The causes are the socioeconomic consequences of having a chronic neurological disease but also adverse effects to antiepileptic drug treatment ranging from interference with calcium and vitamin D metabolism to hyponatremia-induced osteoporosis. Conclusion The literature supports the need for awareness of bone health in patients with epilepsy. The pathophysiological mechanisms are many and various wanting for further research in the less well-characterized areas. Furthermore, great responsibility rests on the healthcare professionals in implementing comprehensive patient care and in assuring bone protective measures in clinical practice to prevent bone loss in patients with epilepsy.

Patients with epilepsy frequently develop hyponatremia due to the treatment with antiepileptic drugs and have an increased risk of developing metabolic bone disease. Hyponatremia is known to be associated with osteoporosis. The aim of the study was to investigate the association between hyponatremia and osteoporosis in patients with epilepsy.This cross-sectional study included patients with epilepsy from a tertiary epilepsy out-patient clinic in Denmark, who had a Dual Energy X-ray Absorptiometry scan performed and an accompanying plasma sodium (p-Na) measured prior to or a maximum of 14 days after the scan. Information regarding the patients' health and medical conditions were obtained from their medical reports.A total of 695 patients (females 53.8%, age 49 (34:63) years (median (quartiles)) were included. 10.4% had hyponatremia (p-Na ≤ 135 mmol/L). The hyponatremic patients had significantly lower T-scores in the lumbar spine, femoral neck and total femur (all p 0.023) and the odds ratio of osteoporosis (T-score -2.5) was significantly increased (2.91 (1.61-5.27) (95% confidence interval) (p = 0.001)). When adjusting for potential confounders the patients with moderate and severe hyponatremia (p-Na 129 mmol/L) had a significantly lower mean T-score in the lumbar spine (p = 0.030).We conclude that hyponatremia is common in patients with epilepsy and that moderate and severe hyponatremia is independently associated with decreased bone mineral density in the lumbar spine. Therefore, hyponatremia in a patient with epilepsy should warrant further examination of the patient for bone loss and osteoporosis.