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Thread: Seizure drugs & Osteoporosis

  1. #1

    Seizure drugs & Osteoporosis

    Greetings Everybody,
    Not sure if this is the right place to post my queries. My bro (47 yrs) has multiple handicaps since childhood (not birth) : spastic on the right side, lost hearing, speech that can be understood only by close family, and vulnerability to epileptic seizures. He has been on a combination of tegrital, eptoin and gardenal for around 17 years. Recently suffered fracture of the hip (believed to have occurred during a seizure). The hip replacement surgery has gone off well. Now the docs have been calling for a change of his epilepsy meds as thse are believed to have led to weakening of his bones which resulted in the major fracture.

    My worry : The neuro has recommended a phased withdrawal of eptoin and replacement with valparin. I had noticed that when a similar replacement of eptoin with valparin was attempted 17 years back he had adverse reactions, by way of repeated attacks, as a result of which the changeover was reversed and eptoin was restored.

    Now I have been scouring the net for adverse effects of eptoin but did not find any mention of bone weakening. About three docs have told me that the combo of tegrital-eptoin-gardenal is bad for bone strength. Are there members here who have knowledge of or experience with (i) the side effects of these drugs, (ii) the alternatives available (iii) whether valparin is indeed to be preferred to eptoin ? Thanks very much for your kind inputs, and my apologies if I have posted this in the wrong place.

  2. #2
    Quote Originally Posted by karegiver View Post
    Greetings Everybody,
    Not sure if this is the right place to post my queries. My bro (47 yrs) has multiple handicaps since childhood (not birth) : spastic on the right side, lost hearing, speech that can be understood only by close family, and vulnerability to epileptic seizures. He has been on a combination of tegrital, eptoin and gardenal for around 17 years. Recently suffered fracture of the hip (believed to have occurred during a seizure). The hip replacement surgery has gone off well. Now the docs have been calling for a change of his epilepsy meds as thse are believed to have led to weakening of his bones which resulted in the major fracture.

    My worry : The neuro has recommended a phased withdrawal of eptoin and replacement with valparin. I had noticed that when a similar replacement of eptoin with valparin was attempted 17 years back he had adverse reactions, by way of repeated attacks, as a result of which the changeover was reversed and eptoin was restored.

    Now I have been scouring the net for adverse effects of eptoin but did not find any mention of bone weakening. About three docs have told me that the combo of tegrital-eptoin-gardenal is bad for bone strength. Are there members here who have knowledge of or experience with (i) the side effects of these drugs, (ii) the alternatives available (iii) whether valparin is indeed to be preferred to eptoin ? Thanks very much for your kind inputs, and my apologies if I have posted this in the wrong place.
    You should look in the medical literature. Do the search with Google Scholar. In any case, I did a quick search and found the following articles from 2008-2010 on Pubmed.

    • Gniatkowska-Nowakowska A (2010). Fractures in epilepsy children. Seizure 19: 324-5. Outpatient Clinic of Child Neurology and Epileptology, 25-565 Kielce, Kosciuszki Str. No. 52/012, Poland. ankagn@mp.pl. PURPOSE: To describe a greater risk of fractures (about 2-6 times more often) in epilepsy children than in children without epilepsy. METHODS: This article describe 126 epilepsy children in age 7-16 who were treated with Antiepileptic Drugs (AEDs) in mono and add-on therapy during 5 years. In the control group were 132 children in age 7-16 without epilepsy and not treated with AEDs, observed in Outpatient Clinic due to headache for 5 years. In both groups we measured bone mineral density (BMD), the calcium and phosphate levels in blood and urine and frequency of fractures. We analyzed both groups statistically (Mann-Whitney test). RESULT: The frequency of fractures is 2-3 times greater in children with epilepsy then in the control group. Osteoporosis and osteopenia is more often present in children who have taken AEDs. Differences in calcium and phosphate levels in blood and urine between study and control group are statistically significant (p<0.001). CONCLUSION: Fractures are an important adverse effect in children who are taking AEDs.
    • Chong DJ and Bazil CW (2010). Update on anticonvulsant drugs. Curr Neurol Neurosci Rep 10: 308-18. Columbia Comprehensive Epilepsy Center, Department of Neurology, Columbia University, 710 West 168th Street, 7th Floor, New York, NY 10032, USA. dc2223@mail.cumc.columbia.edu. In 2009, the US Food and Drug Administration approved three medications for the treatment of epilepsy: rufinamide, lacosamide, and vigabatrin. In addition, extended-release formulations of lamotrigine and levetiracetam were approved recently. When added to the dozen medications for treating epilepsy, the choice is a luxury in terms of additional options, but also a challenge for practitioners to use them all with expertise. Recently, there has been much interest surrounding medications for epilepsy and their possible association with osteoporosis, safety during pregnancy, biological equivalence to generic versions, and possible association with higher rates of suicidality. This review discusses these issues and provides a current overview for the medical management of epilepsy.
    • Leppik IE and Birnbaum AK (2010). Epilepsy in the elderly. Ann N Y Acad Sci 1184: 208-24. Department of Neurology, University of Minnesota, and MINCEP Epilepsy Care, Minneapolis, Minnesota, USA. leppi001@umn.edu. The elderly, often defined as those 65 years or older, are the most rapidly growing segment of the population, and onset of epilepsy is higher in this age group than in any other. This paper reviews recent developments, including a new proposed definition of epilepsy, a transgenic mouse model of Alzheimer's disease that exhibits complex partial seizures, evidence that the highest incidence of epilepsy may occur after admission to a nursing home, a challenge to the vitamin D hypothesis of osteoporosis associated with antiepileptic drugs (AEDs), evidence that the genetic complement of hepatic isoenzymes is more predictive of metabolic rate than age, and data showing that there is considerable variability in serum levels of AEDs in many nursing home residents during constant dosing conditions.
    • Moro-Alvarez MJ, Diaz Curiel M, de la Piedra C, Marinoso ML and Carrascal MT (2009). Bone disease induced by phenytoin therapy: clinical and experimental study. Eur Neurol 62: 219-30. Internal Medicine, Metabolic Bone Disease Unit H, Central Cruz Roja, Madrid, Spain. mjmoro.hccruzr@salud.madrid.org. Previous studies have made references to prolonged treatment with phenytoin as a possible risk factor in the development of osteoporosis and/or osteomalacia. We studied a group of 30 epileptic patients who were under long-term treatment with phenytoin (DPH) in an ambulatory regimen. We found the prevalence of osteoporosis to be 3.3% and of osteopenia to be 56.6%, affecting predominantly the femur, without any significant decrease in bone mineral density of the lumbar spine. These patients were showing signs of bone turnover uncoupling with increases in bone resorption markers. At this time, they also exhibited slight alterations in their phosphocalcium metabolism with trends to hypocalcemia and secondary hyperparathyroidism that was found not to be caused by a vitamin D deficiency as the serum levels of 25(OH)D and 1,25(OH)(2)D were normal. With the aims of corroborating these results and to investigate the physiopathological effects on the bone induced by anticonvulsant drugs we developed a further experimental study in which we administered DPH over a 6-week period with a dose of 5 g/kg/day to male Wistar rats that were in the growth phase. This treatment produced a decrease in overall BMD and bone mineral content in the femur. We did not find osteomalacia in the vertebral biopsy, but the administration of DPH to these animals decreased trabecular volume as well as lessened the thickness of osteoid edges together with an uncoupling in bone turnover. There was also a marked decrease in bone formation and a tendency towards increased bone resorption. We have also found a decrease in resistance to fracture by torsion in the biomechanical assay, which translates into an increase in bone fragility. In these male Wistar rats, the administration of DPH produced a tendency towards increasing the markers of resorption and, though changes in serum levels of calcium and phosphorus were not observed, to provoke an increase in the parathyroid hormone levels; with normal levels of 1,25(OH)(2)D which has produced the same inclination in rats as in humans.
    • Elliott JO (2009). Possible methods for the prevention of bone loss in persons with epilepsy. Expert Rev Neurother 9: 797-812. Department of Neurology, Comprehensive Epilepsy Center, 395 West 12th Avenue, 7th Floor, Columbus, OH 43210, USA. john.elliott@osumc.edu. Various antiepileptic drugs are known to cause bone mineral density (BMD) loss in persons with epilepsy. In general population studies, physical activity has a profound effect on bone health. Vitamin D deficiency, common in persons with epilepsy, is also associated with various chronic health conditions and osteoporosis in the general population. People with epilepsy would benefit from interventional research focused on the prevention of BMD loss. Exercise, healthy dietary habits and nutritional supplementation are important for the development and maintenance of bone health as well as for the prevention of comorbid conditions that are common in epilepsy. Consensus guidelines are needed for the prevention, screening and treatment of BMD loss in epilepsy.
    • Phabphal K, Geater A, Leelawattana R, Sathirapunya P, Sattawatcharawanich S and Limapichat K (2009). Prevalence and risk factors of low bone mineral density and 25-hydroxyvitamin D status in young healthy epileptic adult patients in a tropical Asian country taking antiepileptic drug. Bone 45: 232-7. Division of Neurology, Department of Internal medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand. pkanitpo@medicine.psu.ac.th. PURPOSE: Antiepileptic drugs have been reported to reduce bone mineral density (BMD) in several countries with varying prevalence but in studies with small sample size and inadequate assessment of confounders, and rarely including young adults. We sought to determine the prevalence, vitamin D status and risk factors for low BMD in young adult epileptic patients in a tropical setting. METHODS: We prospectively examined left femoral neck and spine with dual-energy X-ray absorption. Demographic data, basic laboratory studies, history of clinical epilepsy, parathyroid hormone and vitamin D level were obtained. RESULTS: One hundred and twenty three patients were included. The mean (+/-SD) T-score was -0.31+/-1.24 at the spine and -0.19+/-1.11 at the left femoral neck. 36% had osteopenia and 4.1% had osteoporosis at either site. Four patients had vitamin D deficiency. Vitamin D levels were not correlated with BMD. Twenty-five patients had vitamin D insufficiency. Multivariate logistic regression analysis identified low body mass index (BMI) and male sex as risk factors for low BMD at the spine and low BMI and duration of treatment as risk factors for low BMD at the left femoral neck. CONCLUSION: Chronic use of antiepileptic drug (AED) in young adult patients is associated with low BMD.
    • Crawford PM (2009). Managing epilepsy in women of childbearing age. Drug Saf 32: 293-307. The Special Center for Epilepsy, York District Hospital, York, UK. pamela.crawford@york.nhs.uk. Epilepsy affects the menstrual cycle, aspects of contraception, fertility, pregnancy and bone health in women. It is common for seizure frequency to vary throughout the menstrual cycle. In ovulatory cycles, two peaks can be seen around the time of ovulation and in the few days before menstruation. In anovulatory cycles, there is an increase in seizures during the second half of the menstrual cycle. There is also an increase in polycystic ovaries and hyperandrogenism associated with valproate therapy. There are no contraindications to the use of non-hormonal methods of contraception in women with epilepsy. Non-enzyme-inducing antiepileptic drugs (AEDs) [valproate, benzodiazepines, ethosuximide, levetiracetam, tiagabine and zonisamide] do not show any interactions with the combined oral contraceptive (OC). There are interactions between the combined OC and hepatic microsomal-inducing AEDs (phenytoin, barbiturates, carbamazepine, topiramate [dosages>200 mg/day], oxcarbazepine) and lamotrigine. Pre-conception counselling should be available to all women with epilepsy who are considering pregnancy. Women with epilepsy should be informed about issues relating to the future pregnancy, including methods and consequences of prenatal screening, fertility, genetics of their seizure disorder, teratogenicity of AEDs, folic acid and vitamin K supplements, labour, breast feeding and care of a child. During pregnancy, the lowest effective dose of the most appropriate AED should be used, aiming for monotherapy where possible. Recent pregnancy databases have suggested that valproate is significantly more teratogenic than carbamazepine, and the combination of valproate and lamotrigine is particularly teratogenic. Most pregnancies in women with epilepsy are without complications, and the majority of infants are delivered healthy with no increased risk of obstetric complications in women. There is no medical reason why a woman with epilepsy cannot breastfeed her child. The AED concentration profiled in breast milk follows the plasma concentration curve. The total amount of drug transferred to infants via breast milk is usually much smaller than the amount transferred via the placenta during pregnancy. However, as drug elimination mechanisms are not fully developed in early infancy, repeated administration of a drug such as lamotrigine via breast milk may lead to accumulation in the infant. Studies have suggested that women with epilepsy are at increased risk of fractures, osteoporosis and osteomalacia. No studies have been undertaken looking at preventative therapies for these co-morbidities.
    • Tsiropoulos I, Andersen M and Hallas J (2009). Adverse events with use of antiepileptic drugs: a prescription and event symmetry analysis. Pharmacoepidemiol Drug Saf 18: 483-91. Department of Neurology, Odense University Hospital, Odense C, Denmark. iotsi@dadlnet.dk. PURPOSE: To assess adverse events with use of antiepileptic drugs (AEDs) by the method of sequence symmetry analysis. METHODS: We used data from two population-based sources in Funen County, Denmark (population 2006: 479,000); prescription data from Odense University Pharmacoepidemiological Database (OPED) for the period of 1 August 1990-31 December 2006, and diagnoses from the County Hospital register for the period of 1994-2006 to perform sequence symmetry analysis. The method assesses the distribution of disease entities and prescription of other drugs (ODs), before and after initiation of AED treatment, as asymmetry in these distributions may indicate adverse events of AED use. Crude and adjusted sequence ratios (ASRs) with 95% confidence intervals (CI) were calculated. RESULTS: We identified 24,882 incident AED users during the study period. Analysis with predefined drugs and diagnoses detected known AED adverse events of unspecific (constipation, nausea) and specific character (hyponatraemia, osteoporosis). Unanticipated signals from analysis without any preselection of drugs and diagnoses were the association of topiramate with dopaminergic agents (ASR 10.4; 95%CI 1.5-448), of gabapentin with glaucoma (ASR 8.0; 95%CI 1.1-355) and of valproic acid with hypothyroidism (ASR 8.0; 95%CI 1.1-355). CONCLUSIONS: Few unsuspected adverse AED effects were recognized in our study. Sequence symmetry analysis is a feasible method of monitoring for adverse AED effects.
    • May TW, Pfafflin M, Coban I and Schmitz B (2009). [Fears, knowledge, and need of counseling for women with epilepsy. Results of an outpatient study]. Nervenarzt 80: 174-83. Gesellschaft fur Epilepsieforschung, Koordinierungszentrum fur Studien in der Epileptologie, Maraweg 13, 33617, Bielefeld, Deutschland. Theodor.May@evkb.de. BACKGROUND: Women with epilepsy are particularly affected by their condition and need therefore specific counseling and comprehensive information about issues related to contraception, pregnancy, hormone effects on seizure control, bone mineral density, etc. The primary aim of this study was to investigate the knowledge of women with epilepsy about their condition and their need for information and counseling. METHODS: A total of 365 women with epilepsy aged from 16 to 75 years of age took part in this prospective, cross-sectional study. All were treated by neurologists in private practice or outpatient clinics. The physicians distributed anonymous questionnaires to the women, who mailed them unsigned to the Society for Epilepsy Research. Sociodemographic and epilepsy-specific data of the women, their experiences and fears regarding partnership, family planning, pregnancy, care of children, and their self-rated and actual knowledge were assessed. RESULTS: Most women (80.9%) lived together with partners, and about half of the women (44.9%) had children. The majority of those with children were greatly worried during pregnancy about risks to their newborn child. They were afraid of potential handicaps (57.9%) and potential epileptic seizures of the child (52.5%) because of their own epilepsy or antiepileptic drugs. Another 39.0% had had great reservations about becoming pregnant. About every fifth woman (18.2%) stopped or reduced antiepileptic medication during pregnancy without consulting her doctor. Women who consciously abstained from having own children (n=87, 23.8%) often reported epilepsy-related reasons (e.g. risk of malformation caused by antiepileptic drugs, 40.8%). Epilepsy also affects the mother-child relationship. For example 40.8% of the women were worried that the child could be harmed during a mother's seizure and 36% reported that their seizures would frighten their children. About 56-66% of the epileptic women stated that they were well to very well informed about topics on contraception, pregnancy, prophylaxis of malformations, and heredity of epilepsies. The knowledge questionnaires revealed however considerable knowledge deficits. These were especially widespread concerning older women and epilepsy, e.g. antiepileptic drugs and osteoporosis, and more pronounced in older women (>50 years) and those with low school education. In all, self-rated and actual knowledge correlated only slightly (r=0.25). Of the women, 60% preferred personal counseling by their physicians. However, especially younger women wanted further information, primarily easy-to-understand brochures (32%) and educational courses (31%). CONCLUSION: Our results are in accordance with other studies from Great Britain and the U.S. They confirm that women with epilepsy have considerable deficits in epilepsy-specific knowledge and a great need of counselling and information.
    • Pack AM and Walczak TS (2008). Bone health in women with epilepsy: clinical features and potential mechanisms. Int Rev Neurobiol 83: 305-28. Columbia University, New York, NY 10032, USA. Bone disease is recognized as an important pathologic process to identify and treat in women. Women are at greater risk than men secondary to multiple factors including estrogen loss in menopause. The most important consequence of bone disease is fracture. Fracture rates are higher in persons with epilepsy treated with antiepileptic drugs (AEDs). Increased bone turnover secondary to AED exposure, higher rates of osteoporosis, adverse effects on bone quality, seizures, and impaired coordination may all contribute. There is a differential effect of AEDs on bone. Although results are mixed for some AEDs, phenytoin use is consistently associated with lower bone mineral density (BMD). As most evidence associates cytochrome P450 enzyme-inducing AEDs with abnormalities in bone, the induction of these enzymes has been proposed as the main mechanism to describe this effect. However, data suggest that this theory does not explain all findings. Many therapies are available for the treatment of bone disease, but there is limited study in persons with epilepsy. All patients should receive at least the recommended daily allowance of calcium and vitamin D and obtain vitamin D status screening. For prolonged AED exposure, BMD screening is available, particularly if the patient has other risk factors.
    • Phabphal K, Limapichat K, Sathirapanya P, Setthawatcharawanich S, Leelawattana R, Thammakumpee N, Thamaprasit A and Geater A (2008). Bone mineral density following long-term use of antiepileptic drugs in a tropical Asian country. Epileptic Disord 10: 213-8. Division of Neurology, Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand. pkanitpo@medicine.psu.ac.th. The objective of this study was to investigate bone mineral density (BMD) in Thai epileptics who had been receiving long-term, antiepileptic drugs. Subjects were epileptic patients aged 15 to 50 years who had been taking antiepileptic drugs for longer than six months. All were free of disease and none was taking any medication that might interfere with bone metabolism other than antiepileptic drugs. BMD at the left femoral neck and spine was measured with dual energy X-ray absorptiometry. Demographic data, basic laboratory studies and history of clinical epilepsy were obtained. One hundred and thirty patients (63 males and 67 females) were included. Mean age (+ SD) was 31.9 +/- 9.7 year. There were 79 patients receiving monotherapy and 51 patients receiving polytherapy. All patients had normal serum calcium. Thirteen patients had slightly low serum phosphate levels. The BMD at the femoral neck had a mean Z-score - 0.15 +/- 1.17 and the mean Z-score at the lumbar spine was - 0.56 +/- 1.03. Thirty one patients had osteopenia at the spine and 30 patients at the femoral neck. Three patients had osteoporosis of the spine and 1 patient of the femoral neck. There was found to be no significant correlation between age, sex, body mass index, duration of treatment and type of antiepileptic drug with bone mineral density at the femur and spine. The mean BMD of long-term antiepileptic users was lower than that of the sex and age-adjusted mean.
    • Ensrud KE, Walczak TS, Blackwell TL, Ensrud ER, Barrett-Connor E and Orwoll ES (2008). Antiepileptic drug use and rates of hip bone loss in older men: a prospective study. Neurology 71: 723-30. VA Medical Center, One Veterans Drive (111-0), Minneapolis, MN 55417, USA. ensru001@umn.edu. OBJECTIVE: To test the hypotheses that older community dwelling men taking non-enzyme-inducing antiepileptic drugs (NEIAEDs) and those taking enzyme-inducing antiepileptic drugs (EIAEDs) have increased rates of hip bone loss. METHODS: We ascertained antiepileptic drug (AED) use (interviewer-administered questionnaire with verification of use by containers) and measured hip bone mineral density (BMD) (using dual energy x-ray absorptiometry) at baseline and an average of 4.6 years later in a cohort of 4,222 older community-dwelling men enrolled in the Osteoporotic Fractures in Men study. Men were categorized as nonusers (no AED use at either examination, n = 4060), NEIAED user (use of NEIAED only at either examination, n = 100), or EIAED user (use of EIAED only at either examination, n = 62). RESULTS: After adjustment for multiple potential confounders (age, race, clinic site, health status, pain interfering with work or activity, physical activity, smoking status, alcohol use, total calcium intake, diabetes, chronic kidney disease, vitamin D supplement use, bisphosphonate use, selective serotonin reuptake inhibitor use, inability to rise from a chair, body mass index, and baseline BMD), the average rate of decline in total hip BMD was -0.35%/year among nonusers compared with -0.53%/year among NEIAED users (p = 0.04) and -0.46%/year among EIAED users (p = 0.31). Multivariable adjusted rate of loss was -0.60%/year among men taking NEIAED at both examinations, -0.51%/year among men taking NEIAED at one examination only, and -0.35%/year among nonusers (p for trend = 0.03). Findings were similar at hip subregions. CONCLUSION: Use of non-enzyme-inducing antiepileptic drugs was independently associated with increased rates of hip bone loss in this cohort of older community-dwelling men.
    • Vestergaard P (2008). Changes in bone turnover, bone mineral and fracture risk induced by drugs used to treat epilepsy. Curr Drug Saf 3: 168-72. Department of Endocrinology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark. p-vest@post4.tele.dk. Antiepileptic drugs (AEDs) have traditionally been associated with osteoporosis. However, recent studies have only shown a very limited increase in the risk of fractures with the use of some but not all AEDs. Patients with epilepsy have an increased risk of fractures, but this increase is mainly linked to fractures sustained during seizures. Patients with epilepsy may also have a decreased bone mineral density but this decrease is far too small to explain the increase in fracture risk. The decrease in bone mineral density is seen mainly in children with complicating diseases and developmental disorders that lead to vitamin D deficiency. Much of the increase in fracture risk may be due to the underlying disorder and the severity of seizures rather than to the drugs used to treat epilepsy. The prevention of seizures seems to be of greater importance than any potential detrimental effects of the AEDs on the skeleton, provided that vitamin D status is kept at an optimal level. From a fracture point of view most AEDs seem to be relatively safe.
    • Lyngstad-Brechan MA, Tauboll E, Nakken KO, Gjerstad L, Godang K, Jemtland R and Bollerslev J (2008). Reduced bone mass and increased bone turnover in postmenopausal women with epilepsy using antiepileptic drug monotherapy. Scand J Clin Lab Invest 68: 759-66. Department of Neurology, Division for Clinical Neuroscience, Section for Adult Epileptology, Rikshospitalet University Hospital, Oslo, Norway. OBJECTIVES: The aims of this study were to assess the occurrence of osteoporosis and fracture rate in Norwegian postmenopausal women with epilepsy using antiepileptic drugs (AEDs), and to investigate how AEDs may affect bone health. MATERIAL AND METHODS: Twenty-six female patients receiving AED monotherapy and 26 individually matched healthy controls answered questions about their general health, lifestyle and previous fractures. For both groups, bone mineral density (BMD) was measured by DEXA, and serum samples were analysed for biochemical bone turnover markers and haematological parameters. RESULTS: The patients, particularly those treated with enzyme-inducing AEDs, had significantly lower BMD than the controls. Additionally, 62 % of the women with epilepsy had osteoporotic T-values in one or more regions, compared with 27 % in the control group. There was a non-significant tendency towards an increased fracture rate among the patients. Markers for bone formation (ALP, bALP, osteocalcin) and bone resorption (Crosslaps) were elevated in the patient group compared with the controls. CONCLUSIONS: Compared with the healthy controls, we found an increased occurrence of osteoporosis, probably due to increased bone turnover, among Norwegian postmenopausal women with epilepsy undergoing AED monotherapy, which may render these women especially vulnerable to fractures.
    • Vanheer P, van Rhijn J, Boel M, Lagae L, Molenaers G, Adam A and Ceulemans B (2008). Supracondylar femur fracture complicating epileptic insult: a specific and under diagnosed complication? Acta Neurol Belg 108: 17-20. Rehabilitation and Epilepsy Centre for Children and Youth, Pulderbos, Belgium. PURPOSE: In epileptic patients fractures are six times more frequent than in the general population. Known predisposing factors are anticonvulsant drugs, malnutrition, lack of physical activity and sunlight exposure. METHODS: In this study we describe two patients, one with a bilateral supracondylar fracture and one with a unilateral supracondylar fracture after an epileptic seizure. The literature concerning femur fracture following an epileptic insult is reviewed. RESULTS: A review of the literature revealed several cases of femur fractures associated with epilepsy, however no cases were found involving a supracondylar femur. CONCLUSIONS: Our hypothesis is that a tonic seizure with simultaneous contraction of both agonists and antagonists can cause this type of fracture in predisposing patients.
    • Elliott JO, Lu B, Moore JL, McAuley JW and Long L (2008). Exercise, diet, health behaviors, and risk factors among persons with epilepsy based on the California Health Interview Survey, 2005. Epilepsy Behav 13: 307-15. Department of Neurology, Ohio State University, Columbus, OH, USA. john.elliott@osumc.edu. Based on the 2005 California Health Interview Survey, persons with a history of epilepsy report lower educational attainment, lower annual income, and poorer health status, similar to other state-based epidemiological surveys. Previous studies have found persons with epilepsy exercise less and smoke more than the nonepilepsy population. The medical literature has also shown that antiepileptic drugs may cause nutritional deficiencies. Persons with a history of epilepsy in the 2005 CHIS report they walk more for transportation, drink more soda, and eat less salad than the nonepilepsy population. Exercise and dietary behaviors at recommended levels have been found to reduce mortality from many comorbid conditions such as cardiovascular disease, stroke, depression, anxiety, and osteoporosis for which persons with epilepsy are at increased risk. Health professionals in the epilepsy field should step up their efforts to engage patients in health promotion, especially in the areas of exercise, diet, and smoking cessation.
    • El-Hajj Fuleihan G, Dib L, Yamout B, Sawaya R and Mikati MA (2008). Predictors of bone density in ambulatory patients on antiepileptic drugs. Bone 43: 149-55. Calcium Metabolism and Osteoporosis Program, American University of Beirut, Beirut, Lebanon. gf01@aub.edu.lb. BACKGROUND AND AIM: Antiepileptic drugs are associated with bone loss and fractures. Data in children is scarce and the impact of new therapies and of low vitamin D is not clear. This study assessed predictors of bone mineral density (BMD) in 225 ambulatory patients with epilepsy. METHODS: BMD and detailed clinical information were obtained from 137 adults mean age of 31 years, on therapy for a mean of 11.7 years, and 88 children mean age of 13 years, on therapy for an average of 4.7 years. RESULTS: Hypovitaminosis D was common in epileptic patients. BMD was reduced in adults but not children with epilepsy, by 0.3-0.6 SD depending on the skeletal site measured, compared to controls. Duration of treatment, but not vitamin D levels, was negatively correlated with BMD at the hip in adults. Bone density was reduced with the use of both enzyme and non-enzyme-inducing drugs, with both mono- and polytherapy, and was most severely reduced at the spine and hip with the use of enzyme-inducing drugs. In the multivariate analyses, polytherapy in children and duration of therapy and enzyme-inducing drugs in adults were independent predictors of BMD. CONCLUSION: Antiepileptic drug therapy is associated with low bone density at clinically relevant skeletal sites, projecting into a possible doubling of fracture risk. Age, therapy duration, polypharmacy and the use of enzyme-inducing drugs were risk factors. Newer drugs may be associated with deleterious effects on bone. Skeletal monitoring with varying intervals, depending on the individual risk profile, is indicated.
    • Elwakkad AS, El Elshamy KA and Sibaii H (2008). Fish liver oil and propolis as protective natural products against the effect of the anti-epileptic drug valproate on immunological markers of bone formation in rats. Epilepsy Res 80: 47-56. National Research Center, Dokki, Cairo, Egypt. amanyse@hotmail.com. Epilepsy is a major public health problem affecting nearly 50 million people world wide. Treatment with anti-epileptic drugs (AEDs) is generally chronic if not life long and may be associated with significant metabolic effects including decreased bone mass and increased fractures. The aim of this work was to investigate the protective role of fish liver oil and propolis against the effect of the drug valproate that is widely used for treatment of epilepsy. Group of 40 rats was divided into four groups each contain 10 rats. The first group (group I) is healthy normal rats, as control. Epilepsy was conducted in the rest of the rats. The epileptic rats were divided into three subgroups: group II was epileptic group, supplemented orally with valproate. The third group was epileptic group which supplemented orally with valproate in concomitant with fish liver oil, the last group; group IV was epileptic group which supplemented orally with valproate in concomitant with propolis. In the present study oral administration of valproate to the epileptic rats by a dose of 400mg/kg/daily for six months (group II) resulted in a significant increase of bone alkaline phosphatase, osteocalcin and N-telepeptide of type 1 collagen (NTX) relative to the control group. There were increase of receptor activator of NF kappa B ligand (RANKL), tumor necrosis factor - alpha (TNF-alpha) and decrease of osteoprotegrin (OPG) compared to normal control. Administration of fish liver oil orally in a dose of 0.4mg/kg daily in concomitant with valproate 400mg/kg daily for six months (group III), result in reduction of N-telepeptide of type 1 collagen (NTX) in comparison to group II and with no significant increase than the control (group I). There were high significant increase of bone alkaline phosphatase and osteocalcin compared to control group I. There was high significant increase of bone alkaline phosphatase than group II and increase in osteocalcin, and decrease in N-telepeptide of type 1 collagen (NTX) compared to group II. A significant increase in osteoprotegrin (OPG) in comparison to group II and to control (group I) with a decrease in RANKL compared to group II and with no significant increase than normal control (group I). The TNF-alpha showed a significant decrease compared to group II with no significant increase than normal control. Administration of propolis orally in a dose of 50mg/kg daily in combination with valproate 400mg/kg/daily for six months (group IV) cause increase in bone alkaline phosphatase with no statistical difference between osteocalcin and N-telepeptide of type 1 collagen (NTX) and normal control (group I). There were increase in bone alkaline phosphatase than group II but less than group III. The increase in osteocalcin in-group III (fish oil group) was significantly higher than in-group IV and there was no statistical difference between it and group II. Where the N-telepeptide of type 1 collagen (NTX) the bone resorption marker was significantly higher than Group III and significantly lower than group II. There was a decrease of RANKL in comparison to group II with no significant difference than group III and a significant increase than control group. There was an increase in osteoprotegrin (OPG) in comparison to control (group I), group II and from group III. There was decrease in TNF-alpha than group III, group I and group II. In conclusion, in epileptic rats treated with valproate (which cause osteoporosis) fish liver oil and propolis increase the bone formation markers and decrease the bone resorption one's. They increase the OPG and decrease TNF-alpha, and RANKL which inhibit the osteoclastogenesis. We recommend the use of Fish Oil, or propolis as a prophylactic treatment for epileptic patients using valproate against the side effect of valproate on bone.
    • Chou IJ, Lin KL, Wang HS and Wang CJ (2007). Evaluation of bone mineral density in children receiving carbamazepine or valproate monotherapy. Acta Paediatr Taiwan 48: 317-22. Division of Pediatric Neurology, Department of Diagnostic Imaging, Chang Gung Children's Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan. BACKGROUND: Antiepileptic drugs have been shown to be associated with a lowering of bone mineral density in childhood and adolescence, which are critical periods of skeletal mineralization. A lower peak bone mass attained at the end of adolescence is associated with greater involutional osteoporosis and risk for fracture in the elderly. Our purpose was to evaluate the effects of carbamazepine and valproate monotherapy on bone mineral density in children in Taiwan. METHODS: From November 1995 to April 2005, forty-two children with uncomplicated epilepsy, who were treated with either carbamazepine (n=21) or valproate (n=21) monotherapy for more than 6 months, were enrolled in this study. All subjects were 5 to 18 years of age, seizure-free for 5 months or more, with normal daily activity, and normal diet. Lumbar bone mineral density of L1 to L4 was measured by dual-energy X-ray absorptiometry. RESULTS: The mean serum levels of carbamazepine and valproate were 5.12 +/- 2.15 mcg/ml and 49.61 +/- 20.84 mcg/ml, respectively. Treatment durations were 37.05 +/- 31.11 months and 22.86 +/- 18.84 months, respectively. The serum levels of calcium and phosphate in both groups were within therapeutic range. The serum level of alkaline phosphatase was significantly higher in the carbamazepine group (264.71 +/- 66.91, U/L) than in the valproate group (179.48 +/- 79.37, U/L). Three patients (140%) had bone mineral density Z-score of -2.0 or lower in the carbamazepine-treated group, but none in the valproate-treated group (p=0.232). Comparing the Z-score in carbamazapine- and valproate-monotherapy children, 7 (33%) had Z-score of -1.5 or lower in the carbamazepine-treated group, and none in the valporate-treated group had Z-score of -1.5 or lower (p=0.009). Four (57%) patients in the 7 carbamazepine-treated children with Z-score of -1.5 or lower had serum drug level lower than therapeutic range. CONCLUSIONS: Children receiving carbarmazepine monotherapy had increased frequency of lower bone density than children receiving valproate monotherapy.
    • Briesacher BA, Andrade SE, Fouayzi H and Chan KA (2008). Comparison of drug adherence rates among patients with seven different medical conditions. Pharmacotherapy 28: 437-43. Division of Geriatric Medicine, University of Massachusetts Medical School, Worcester, Massachusetts; Meyers Primary Care Institute, Worcester, MA 01605, USA. Becky.Briesacher@umassmed.edu. STUDY OBJECTIVE: To compare drug adherence rates among patients with gout, hypercholesterolemia, hypertension, hypothyroidism, osteoporosis, seizure disorders, and type 2 diabetes mellitus by using a standardized approach. DESIGN: Longitudinal study. DATA SOURCE: Health care claims data from 2001-2004. PATIENTS: A total of 706,032 adults aged 18 years or older with at least one of the seven medical conditions and with incident use of drug therapy for that condition. MEASUREMENTS AND MAIN RESULTS: Drug adherence was measured as the sum of the days' supply of drug therapy over the first year observed. Covariates were age, sex, geographic residence, type of health plan, and a comorbidity score calculated by using the Hierarchical Condition Categories risk adjuster. Bivariate statistics and stratification analyses were used to assess unadjusted means and frequency distributions. Sample sizes ranged from 4984 subjects for seizure disorders to 457,395 for hypertension. During the first year of drug therapy, 72.3% of individuals with hypertension achieved adherence rates of 80% or better compared with 68.4%, 65.4%, 60.8%, 54.6%, 51.2%, or 36.8% for those with hypothyroidism, type 2 diabetes, seizure disorders, hypercholesterolemia, osteoporosis, or gout, respectively. Age younger than 60 years was associated with lower adherence across all diseases except seizure disorders. Comorbidity burden and adherence varied by disease. As comorbidity increased, adherence among subjects with osteoporosis decreased, whereas adherence among those with hypertension, hypercholesterolemia, or gout increased. Add-on drug therapies and previous experience with taking drugs for the condition increased adherence among subjects with hypertension, type 2 diabetes, hypothyroidism, or seizure disorders but not the other conditions. CONCLUSION: This uniform comparison of drug adherence revealed modest variation across six of seven diseases, with the outlier condition being gout.
    • Elliott JO, Seals BF and Jacobson MP (2008). Osteoprotective knowledge in a multiethnic epilepsy population. J Neurosci Nurs 40: 14-24, 39. Department of Neurology, Comprehensive Epilepsy Center, The Ohio State University, Columbus, OH, USA. John.Elliott@osumc.edu. Antiepileptic drugs (AEDs) are known to cause bone loss. People with epilepsy have twice the fracture rate of nonepilepsy populations. Osteoprotective knowledge related to calcium and exercise has not been assessed in people with epilepsy. The Osteoporosis Knowledge Test (OKT), a validated, 24-item test, was administered to 94 epilepsy patients (28 males and 66 females) to measure knowledge of risk factors for osteoporosis and strategies for prevention related to calcium and exercise. The mean age of participants was 45 years with an average AED exposure of 20 years. Fifty participants were Caucasian and 44 were non-Caucasian. No significant differences related to age or gender for the OKT were found. One-way analysis of variance (ANOVA) of ethnicity showed that non-Caucasians had much lower calcium (F = 8.15, p = .005) and exercise (F = 7.71, p = .007) knowledge. The total mean OKT score was 11.71 (4.92), reflecting a correct response rate of 49%. In previous studies of nonepilepsy populations, the mean OKT score ranged from 7.83 to 21.8, with a correct response ranging from 32.9% to 90.8%. Independent t tests of the individual OKT questions revealed specific knowledge deficiencies in the areas of risk factors, exercise, and reasons for calcium supplementation for non-Caucasians. Results of this study reveal that people with epilepsy, who are at greater risk for metabolic bone loss, have lower knowledge scores for calcium and exercise than nonepilepsy populations of various ages and genders. Culturally relevantepilepsy materials and programs may improve knowledge and adoption of preventative behavior.

    Last edited by Wise Young; 07-28-2010 at 06:27 AM.

  3. #3
    According to a study published in the January issue of Archives of Neurology, most epilepsy drugs are associated with an increased risk of non-traumatic fracture in individuals 50 years of age and older.

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