Epilepsy & Behavior 45 (2015) 217–222

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Survey of risk factors for osteoporosis and osteoprotective behaviors among patients with epilepsy Marianna Fedorenko a,1, Mary L. Wagner a,⁎, Brenda Y. Wu b,2 a Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers University, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA b Department of Neurology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, 125 Patterson Street, New Brunswick, NJ 08901, USA

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Article history: Received 5 November 2014 Revised 26 December 2014 Accepted 4 January 2015 Available online 24 March 2015 Keywords: Epilepsy Osteoporosis Calcium Vitamin D Bone mineral density Exercise Cigarette smoking Co-morbidity

a b s t r a c t The prevalence of risk factors for osteoporosis in persons with epilepsy, patients' awareness of their risk, and their engagement in osteoprotective behaviors were assessed in this study. Two hundred and sixty patients with epilepsy (F = 51.5%, average age = 42) completed a survey tool. Of 106 patients with a dual energy X-ray absorptiometry (DXA) result, 52% had low bone mineral density, and 11% had osteoporosis. The results suggest that the majority of patients with epilepsy do not engage in bone-protective behaviors. Those who have undergone a DXA scan may be more likely to take calcium and vitamin D supplementation compared with those who did not undergo a DXA scan, but they do not engage in other osteoprotective behaviors. Many patients did not accurately report their DXA results, indicating that better patient education is warranted. © 2015 Elsevier Inc. All rights reserved.

1. Introduction Patients with epilepsy are two to six times more likely to fracture a bone compared with the general population [1,2]. While patients with epilepsy are predisposed to fracture due to seizure-related falls, a meta-analysis attributed seizures as a cause for only one-third of the fractures [2]. The risk of falls and subsequent fracture is exacerbated by impaired balance from adverse effects of antiepileptic drugs (AEDs) and/or comorbid neurological deficits [3–5]. Concomitantly, there is a high prevalence of osteopenia and osteoporosis found in the patient population with epilepsy, especially in groups normally considered with a low risk of developing bone disease, such as males under the age of 50 and women in the premenopausal period [1,6–10]. Therefore, bone disease, specifically osteopenia and osteoporosis, contributes to the high fracture rate in this population. Antiepileptic medications increase patients' risk of debilitating osteoporosis. Older enzyme-inducing AEDs (phenytoin, phenobarbital, primidone, and carbamazepine) accelerate vitamin D metabolism and ⁎ Corresponding author. Tel.: +1 848 445 6392. E-mail addresses: [email protected] (M. Fedorenko), [email protected] (M.L. Wagner), [email protected] (B.Y. Wu). 1 Present address: Department of Pharmacy Practice, St. Louis College of Pharmacy, 4588 Parkview Place, St. Louis, MO 63110, USA. 2 Present address: Northeast Regional Epilepsy Group, 303 George Street, Suite 405, New Brunswick, NJ 08901, USA.

http://dx.doi.org/10.1016/j.yebeh.2015.01.021 1525-5050/© 2015 Elsevier Inc. All rights reserved.

adversely affect bone mineral density (BMD), bone quality, and bone turnover. However, other mechanisms, such as a direct effect on bone cells, the endocrine system, and vitamin K, may also cause bone loss as low BMD is observed with AEDs that are not enzyme inducers (e.g., valproic acid) [11–15]. Most likely, multiple factors, in addition to AED exposure, may lead to poor bone health in patients with epilepsy. Other medications prescribed to patients with epilepsy may further increase their risk of bone loss. Depot medroxyprogesterone acetate injection (Depo-Provera®), a progestin-based contraceptive, is often recommended to women of child-bearing age with epilepsy, but studies find that it reduces BMD by as much as 3% in adolescents and young women at an age when increases of BMD are a norm [16–18]. Consequently, Depo-Provera® has a black box warning indicating that women may lose significant BMD, and long-term use (greater than two years) should be limited to patients in whom other birth control methods are inadequate. The bone-reducing effects may be reversible, but studies are lacking to determine whether reaching peak bone mass is impeded by the use of the contraceptive and if it increases risk of fracture at an older age [19–21]. Behavioral risk factors for osteoporosis include low calcium intake, vitamin D insufficiency, increased alcohol intake, inadequate physical activity, smoking, and falling [22]. However, few studies have investigated the prevalence of these risk factors among patients with epilepsy. Population surveys in Ohio, Georgia, and Tennessee using the Behavioral Risk Factor Surveillance System (BRFSS) found that persons with a

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history of epilepsy report that they exercise less frequently and smoke more compared with the general population [23,24]. In contrast, the 2005 California Health Interview Survey (CHIS) found no difference in exercise patterns [25]. To date, there are no studies that determine which risk factors are most prevalent or predict low BMD in patients with epilepsy. Patients with epilepsy may also be less likely to engage in boneprotective behaviors. Awareness among patients with epilepsy of their increased risk of bone disease may increase their likelihood of engaging in bone-protective behaviors [26]. Interestingly, studies of other populations found that patients who were told that they have low BMD results after dual energy X-ray absorptiometry (DXA) testing were more likely to increase dietary calcium, start an exercise program, and stop smoking compared with patients with normal BMD results [27]. Unfortunately, trends in adoption of osteoprotective behaviors in patients with epilepsy have not been studied. Thus, it is important that the relationship between risk factors for osteoporosis and epilepsy be understood in order for better preventative measures to be adopted to minimize the risk of debilitating osteoporosis. This study aimed to assess the following: (1) risk factors for developing osteoporosis in patients with epilepsy and (2) patients' awareness of their risk and engagement in osteoprotective behaviors. 2. Methods 2.1. Subjects Patients visiting the University Medical Group's Epilepsy Clinic at Robert Wood Johnson Clinical Academic Building in New Brunswick, NJ for a regular appointment with their neurologist were asked to complete a survey tool about demographics and behaviors. Patients managed by three neurologists with a specialty in epilepsy participated in the study. Surveys were completed by either the patient or the caretaker or were verbally administered by an investigator from June 2008 to January 2011. We collected survey tools from (1) adult patients ≥ 18 years of age, (2) those with a diagnosis of epilepsy determined by their neurologists, (3) both those who completed a DXA scan and those who did not complete a DXA scan, and (4) those who were fluent in English or had an available translator (phone translator service was used for one patient). Patients who had cognitive impairment and whose caretakers were not present, who experienced seizures during their appointment, or who were uncooperative were excluded. Additionally, the DXA results were retrieved from an existing database, which our research group created to track BMD changes of our patients with epilepsy or from patients' electronic chart when available. All protocols were reviewed and approved by the Institutional Review Board of the University of the Medicine and Dentistry New Jersey (UMDNJ) and Rutgers University, and informed consent was collected from all patients. 2.2. Survey tool The survey tool included a variety of question formats. Patients were asked to fill in their age, gender, sex, height, weight, ethnicity, current AEDs, and number of seizures per month, and they were asked to select from a list of AEDs to determine self-reported lifetime exposure to AEDs. Questions regarding family history of osteoporosis, engaging in weightbearing exercise, smoking cigarettes, drinking one alcoholic beverage in the last month, and fracture history were in a yes/no format. When asked if each patient ever underwent a DXA scan, patients could choose between yes/no/I am not sure. If a patient reported undergoing a DXA scan, they were asked to provide the approximate date of the last DXA scan and to report their result as either “low bone density” or “normal bone density”. For supplement history, patients were asked to select if they currently took calcium, vitamin D, combination product, multivitamins, or other supplements. If a patient reported taking one

or more of the supplements, they were asked to list the dose, brand, or ingredients and to select an intake frequency of less than three times per week or greater or equal to three times per week. To determine dietary calcium intake, we asked patients to calculate the number of servings of calcium-rich foods they ate per day (1 serving = 1 cup of milk, yogurt, or pudding; 1 1/2 slices of cheese; 2 cups of dark vegetables; or 6 oz. of salmon). For frequency of exercise and sunlight exposure, patients were asked to select between less than three times per week and greater or equal to three times per week. Finally, bone health perception was listed on a scale of poor, fair, average, good, or great. Female patients were asked to select if they were menstruating, menopausal, or postmenopausal. The survey tool was not validated, but the questions were adopted from previously published articles, the BRFSS questionnaire, and the National Health and Nutrition Examination Survey (NHANES) [23,28]. 2.3. Data collection Data from the survey tool were entered into an Excel spreadsheet. The DXA results were characterized as low if the t-score was less than or equal to −1.0 SD at either the femoral neck or the L1–L4 spine. Additionally, t-scores between −1.0 and − 2.5 SD were characterized as osteopenic, and less than −2.5 SD were characterized as osteoporotic [22]. Each patient's BMI was calculated using the formula BMI = kg/m2. Patients reporting dual ethnicity (i.e., Black and Italian) were put into the “other” category, and those reporting Indian ethnicity were put into the “Asian” category. Each patient's risk of bone loss was defined by the AEDs they had taken and the presence/absence of osteoporosis risk factors, including engagement in osteoprotective behaviors. Patients who reported a lifetime exposure to phenytoin, phenobarbital, primidone, valproic acid, oxcarbazepine, and/or carbamazepine were identified as higher-risk patients as these drugs are reported to reduce bone density (AED reducers). Categories of AED exposure were also subdivided into low/unknown reducers (levetiracetam, lamotrigine, gabapentin, lacosamide, zonisamide, pregabalin, and topiramate), medium reducers (oxcarbazepine and valproic acid), and strong reducers (phenytoin, phenobarbital, carbamazepine, and primidone). Patients were characterized as having poor seizure control if they met the following criteria: three or more convulsive seizures in different occasions per year, three or more complex partial seizures per year, status epilepticus within one year, and/or frequent episodes of behavioral outburst with uncontrolled psychiatric symptoms and confusion. Patients who completed a DXA scan were compared with patients who did not complete a DXA scan. We hypothesized that patients reporting having undergone a DXA scan would have a higher rate of osteoprotective behaviors compared with those not reporting having undergone a DXA scan. Post hoc analysis included comparing patients who reported having low bone mineral density with those who reported having normal bone mineral density; comparing patients with the presence of risk factors for osteoporosis (age greater than fifty, family history of osteoporosis, postmenopausal, and BMI less than 19 kg/m2) with those without risk factors, comparing patients with a family history of osteoporosis with those without, comparing male patients with female patients, comparing patients who had good perception of bone health with those who had poor perception of bone health, and comparing patients with good seizure control with those with poor seizure control. The patients' DXA scan results were correlated with their perception of their bone health. 2.4. Data analysis Survey tool data were converted to categorical values. “Adequate dietary calcium” was defined as greater than or equal to 3 servings of calcium-rich food per day, “regular intake of calcium and vitamin D supplementation” as calcium and vitamin D supplementation (either a

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combination product or as individual products) greater than or equal to 3 times per week, “adequate weight-bearing exercise” as engaging in weight-bearing exercise greater than or equal to 3 times per week, and “poor bone health perception” as perceiving bone health as poor, fair, or average. 2.5. Statistical analysis A t-test was performed for means and chi-square analysis for percentages using Microsoft Excel. 3. Results 3.1. Demographics Over a two-and-a-half-year period, 260 patients were surveyed. Slightly more than half (51.5%) of the patients were female, the mean age was 41.9 ± 15.5 years old, and the mean BMI was slightly overweight (28.2 ± 8.6 kg/m2). The majority of patients who selfidentified as White (62.0%), Black (13.6%), and Hispanic (14.0%) were the next largest ethnicity groups. Nearly half (48.8%) of the patients had poor seizure control, and a majority of patients reported previous exposure to "a bone-reducing AED" (65.8%). A positive family history of osteoporosis was reported by 23.4% of the patients, and 38.4% (99 of 258 patients who answered the fracture question) reported experiencing a fracture in his/her lifetime (Table 1). Of these patients, 13 (5.0%) experienced a seizure-related fracture. Of 166 reported lifetime fractures, 27 (16.3%) were described as seizure-related. Less than half (116 of 260, 44.6%) of the patients claimed to have a DXA scan performed, and 96 of these patients specifically indicated the result of their DXA (low BMD vs. normal BMD). Of the 96 patients, 38 (39.5%) patients reported that their DXA scan results indicated low BMD. When asked about bone health perception, 17.5% of the patients believed that they had poor bone health. The DXA scan results were retrieved for 106 patients, and 55 (51.9%) patients were identified to have low BMD or osteoporosis; specifically, 12 (11.3%) patients had osteoporosis. 3.2. Osteoprotective behaviors Slightly less than half of the patients were engaging in osteoprotective behaviors. Only 33.1% reported adequate daily dietary calcium, with a Table 1 Demographics for total population and patients who reported undergoing a DXA scan and those who did not report undergoing a DXA scan. Outcome

Total (n)

With DXA

Without DXA

N Agea Female BMI (kg/m2)

260 41.9 ± 15.5 51.5% 28.2 ± 8.6

116 45.2 ± 15.2 56.9% 27.7 ± 6.6

139 39.0 ± 15.2 46.8% 28.7 ± 10.0

Ethnicity Whiteb Black Hispanic Asian Other Years of taking AED (median) AED reducers Poor seizure controlb Family history of osteoporosis Fracture history

62.0% 13.6% 14.0% 8.9% 1.6% 6.0 65.8% 48.8% 23.4% 38.4%

70.7% 10.3% 11.2% 6.0% 1.7% 6.0 67.0% 40.5% 22.7% 36.5%

55.5% 16.1% 15.3% 11.7% 1.5% 6.0 63.5% 55.4% 24.1% 39.9%

Note: values are represented as percentage %; DXA = dual energy X-ray absorptiometry; BMI = body mass index (kg/m2); AED = antiepileptic drug; AED reducers = history of exposure to carbamazepine, phenytoin, phenobarbital, primidone, valproic acid, and oxcarbazepine; t-test or chi-square analysis performed where appropriate to compare the group with DXA with the group without DXA. a p-Value b 0.001. b p-Value b 0.05.

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Table 2 Osteoprotective behaviors for total population and patients who reported undergoing a DXA scan and those who did not report undergoing a DXA scan. Outcome

Total

With DXA

Without DXA

N Adequate dietary calcium Servings of calcium per day Regular intake of calcium/vitamin D supplementa Adequate weight-bearing exercise Adequate sunlight exposure Alcohol Smoking Multivitamin intake Poor bone health perception

260 33.1% 2.3 ± 1.85 25.4% 28.1% 50.2% 26.2% 16.5% 41.9% 17.5%

116 31.9% 2.2 ± 2 34.2% 29.3% 55.4% 31.0% 18.1% 47.4% 21.1%

139 34.6% 2.4 ± 1.7 20.2% 26.7% 50.7% 23.0% 15.8% 36.0% 13.5%

Note: values are represented as percentage %. Poor bone health perception = self-rated bone health as poor, fair, or average on a categorical scale of poor, fair, average, good, or great. Chi-square analysis was performed to compare the group with DXA with the group without DXA. a p-Value b 0.01.

mean of 2.3 calcium-rich servings per day. Of patients who answered the survey item, 25.4% reported regular intake of calcium and vitamin D supplements, 28% engaged in adequate weight-bearing exercise, and 50.2% had adequate sunlight exposure. Current smoking history was reported by 16.5% of the patients (Table 2). 3.2.1. Comparing patients with a DXA scan with those without a DXA scan Patients who reported to have undergone a DXA scan were older (45.2 ± 15.2 vs. 39.0 ± 15.2, p b 0.001), were more likely to selfidentify as White compared with other ethnicity groups (p = 0.02), and were more likely to report a regular intake of calcium and vitamin D supplements (34.2% vs. 20.2%, p b 0.004) compared with patients who did not report undergoing a DXA scan. Patients who reported undergoing a DXA scan were also less likely to have poor seizure control (40.5% vs. 55.4%, p b 0.03) compared with patients who did not report undergoing a DXA scan. All other demographic and behavioral factors were similar (Table 2). 3.2.2. Comparing patients with perceived low BMD with those with perceived normal BMD Post hoc analysis was completed to compare patients who thought that their DXA scan indicated low BMD with patients who thought that their DXA scan indicated normal BMD. Patients who thought that they had low BMD had a lower BMI (25.8 ± 6.9 vs. 29.5 ± 5.66, p b 0.008) compared with patients who thought that they had normal BMD. Patients who thought that they had low BMD were also more likely to have poor bone health perception (p b 0.004) compared with patients who thought that they had normal BMD. All other evaluated demographic and behavioral factors were similar. 3.2.3. Comparing patients with actual low BMD with those with normal BMD Further analysis was completed for patients from whom a DXA scan was retrieved. Patients with low BMD results on retrieved DXA scan had a lower BMI (26.0 ± 5.5 vs. 29.3 ± 5.9, p b 0.004) compared with patients with normal BMD results. Patients with low BMD were also more likely to have poor bone health perception (p = 0.032) compared with patients with normal BMD. 3.3. Congruency between perceived DXA result and actual DXA result Dual energy X-ray absorptiometry scans were available for 106 of the 260 patients who completed the survey. Of these patients, 17 (16%) reported that they did not undergo a DXA scan, but a DXA scan was found on file; low BMD was reported in six of these patients. Two (2%) patients indicated that they were unsure if they had undergone a

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DXA scan in the past; low BMD was reported in one patient. Perception of having undergone a DXA scan matched (the DXA scan was found on file or in the database) in 87 (82%) patients. Of the 87 patients, only 55 (63%) patients correctly perceived their DXA result (i.e., patients indicated that they had low BMD, and the DXA scan indicated low BMD), perception of 18 (20.7%) patients did not match their DXA result, and 14 (16%) patients were unsure of their DXA result. Of the 14 patients who were unsure of their DXA results, six (42.8%) patients had low BMD. Notably, patients whose DXA scans indicated low BMD were more likely to think that they had low BMD compared with patients whose DXA scans indicated normal BMD (p b 0.0001). 4. Discussion In our sample of 260 patients diagnosed with epilepsy and taking antiepileptic medications, less than half of the patients were engaging in osteoprotective behaviors, even though half of this population had low bone mineral density and more than 10% had osteoporosis. Even more concerning was that the mean age of our patients was only 42 years; thus, by the time they would be routinely screened, many more patients would have osteoporosis. 4.1. Calcium and vitamin D supplementation Adequate lifelong dietary calcium is essential for prevention of osteoporosis. Calcium and vitamin D supplementation has also been found to reduce fracture risk and to decrease bone loss, especially in patients with vitamin D deficiency [29–32]. In patients with epilepsy, highdose vitamin D supplementation (4000 IU per day) led to increased BMD after one year at the lumbar spine, total hip, and radius by about 1% but not at the femoral neck. Although 25 (OH)D levels were within normal range in 69% of the patients at the end of therapy (mean: 26.3 ng/mL) compared with 20% at baseline (mean: 13.8 ng/mL), BMD was not normalized compared with age- and ethnicity-matched controls. Notably, mean dietary calcium intake reached only 600 mg per day instead of the recommended 1200 mg per day [33]. Results of other studies with high-dose vitamin D (2000–4000 IU per day and 120,000 IU one time) are conflicting; some show increased BMD or BMC [34–36], while another did not [37]. Mikati suggests that highdose vitamin D supplementation may only increase BMD in patients with low baseline BMD [33]. Patients in the study that showed no benefit of vitamin D had normal baseline bone mass, but vitamin D levels were not measured, while patients in the other trials had low baseline bone mass compared with controls. However, many of these studies had small sample sizes, did not account for total dietary intake of calcium and vitamin D, and differed in how they defined BMD changes. For studies in which baseline vitamin levels were measured, a subgroup analysis determining whether vitamin D supplementation benefited only patients with low levels was not conducted. Prospective studies are needed to determine whether reaching a certain vitamin D concentration or the recommended daily dose of calcium (1200 mg per day) is necessary for sufficient BMD increases or maintenance and whether only patients with epilepsy with vitamin D deficiency or low baseline BMD may benefit from high-dose vitamin D supplementation. Recent evidence also suggests that calcium supplementation may increase cardiovascular risk; therefore, emphasis should be placed on increasing dietary calcium intake and other osteoprotective behaviors (e.g., exercise and smoking cessation) and on minimizing the use of medications that adversely affect bone [38]. 4.2. Exercise Although exercise was defined differently, the percentage of our patients with epilepsy engaging in weight-bearing exercise at least three times a week (28%) is less than the percentage of the NJ population doing moderate physical activity (30 min or more, five days or more

per week) or vigorous physical activity (20 min or more, three days or more per week) (47.5%) in 2009 [28]. Weight-bearing exercise is important because it increases BMD, a surrogate marker of fracture risk [39]. Using the 2005 CHIS, Elliot found that patients with epilepsy engaged in similar levels of regular, moderate, and vigorous activities compared with patients without epilepsy [25]. The survey also reported that patients with epilepsy were more likely to report walking at least 10 min for transportation in the past seven days compared with those without a history of epilepsy. However, studies of patients with epilepsy using the Ohio, Georgia, and Tennessee BRFSS found decreased physical activity [23,24]. The conflicting results may be due to the different methods of defining exercise between the studies. For some patients, barriers to exercise may include fear of triggering a seizure, low motivation, and poor health [40]. However, studies in patients with epilepsy indicate that physical activity may decrease seizure frequency as well as lead to improved cardiovascular and psychological health [41]. Thus, patients should be encouraged to do weight-bearing exercises and to participate in exercise programs designed for improving bone health or for reducing barriers to exercise. 4.3. Smoking The percent (16.5%) of patients reporting that they currently smoked is similar to the percent (14.4–15.8%) of patients reporting that they smoked in the state of NJ from 2009 to 2010 [28]. This conflicts with other researchers, who found current smoking rates to be significantly increased (24–39%) and, in some cases, doubled in patients with epilepsy compared with patients without epilepsy (15–25%) [23–25,42]. Since smoking hinders bone health, it is important that patients be referred to smoking cession programs. 4.4. DXA scan Our hypothesis was that rates of osteoprotective behaviors would be higher in patients undergoing a DXA scan than in those not reporting a DXA scan as a result of this targeted patient education. Indeed, patients who claimed to have a DXA scan completed reported significantly higher rates of regular intake of calcium and vitamin D supplementation. However, other osteoprotective behaviors (weight-bearing exercise and smoking) did not differ between patients who report undergoing a DXA scan and patients who did not report undergoing a DXA scan. The majority of the patients in our study were seen by a single neurologist who promoted osteoprotection by referring patients for a DXA scan and by providing prescriptions for calcium and vitamin D supplementation. It is possible that patients with epilepsy from other medical practices may be less likely to undergo a DXA scan, start taking calcium and vitamin D supplements, or engage in other osteoprotective behaviors unless prompted by a practitioner with an interest in bone health. If the neurologist believes that the patient is more at risk of low BMD, based on AED history or weight, combined calcium and vitamin D may be prescribed along with patient education on boneprotective practices. Moreover, patients undergoing a DXA scan were more likely to have well-controlled seizures. The entire DXA scan procedure takes between 10 and 30 min and may require the patient to hold still, which may form a barrier for patients with uncontrolled seizures. Possibly reflecting clinical practice, our neurologist may place priority on obtaining a complete seizure history and adjusting medications during the appointment than referring a patient for a DXA scan. Further research exploring barriers to obtain a DXA scan in patients with poor seizure control is needed. Despite having a sample population in the younger ages (mean age: 43 years) and a mean BMI in the overweight range (27.6 kg/m2), slightly more than half of the patients had low BMD; specifically, 42% had osteopenia, and 11% had osteoporosis. The rates are similar to rates reported in some studies [7,43] but lower than other studies [8,44]. The rate of osteopenia and osteoporosis in our patients is similar to the

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rates of patients fifty years of age or older (10 or more years older than our patients). This may suggest that patients with epilepsy may need to be screened for low BMD at a younger age than the average population [45]. Patients' perception of their DXA result did not always match the actual DXA result, and some patients were unsure of their DXA result. Other studies similarly found a disconnect between the actual DXA result and the perceived DXA result in other patient populations [46,47]. Since our neurologists ordered the majority of the DXA scans included in this study (instead of a primary care physician or an endocrinologist), one may question whether this could contribute to a lack of accurate recall. However, one study found that accuracy of information recalled by patients regarding their DXA result was not affected by the specialty of the clinicians [46]. More studies are needed to examine the causes for patients' misunderstanding of their DXA result. However, it is essential that clinicians verify that their patients understand the meaning of their DXA result and have knowledge of measures to prevent further bone loss. Although our results suggest that patients understand what the DXA scan means, patients with low BMD still reported similar rates of osteoprotective behaviors compared with patients with normal BMD. It appears that a DXA scan result of low BMD did not influence behavior in patients with epilepsy. In contrast, Greenspan found that postmenopausal women with low BMD were more likely to increase dietary calcium, start an exercise program, and stop smoking compared with patients with normal BMD results after undergoing BMD testing [27]. Greenspan's patients were recruited from an Osteoporosis Program at the Women's Health Center and probably received extensive patient education specific to preventing further bone loss. Our neurologists monitor BMD in our patients with epilepsy, but their priority is treating the epilepsy disorder. It is possible that more care should be taken to refer our patients to an osteoporosis clinic or their primary care provider to ensure that adequate education is provided. Moreover, patients with epilepsy may believe that they are less susceptible to having osteoporosis compared with postmenopausal women; therefore, they may be less likely to initiate exercise or increase dietary calcium [48]. A majority of our patients (65.8%) were previously exposed to the older AEDs known to reduce bone loss, which were classified as carbamazepine, phenytoin, phenobarbital, primidone, valproic acid, and oxcarbazepine. A recent study published after our data analysis suggested that topiramate also negatively impacts bone [49]. Therefore, the proportion of patients designated as exposed to bone-reducing AEDs may be artificially low in this study. If possible, clinical decisions should focus on reducing exposure to bone-reducing AEDs. Currently, prospective clinical studies report only lamotrigine and levetiracetam as bone-protective AEDs [50,51]. Interestingly, switching therapy from phenytoin to levetiracetam led to significantly improved BMD and 25hydroxy vitamin D levels compared with patients with epilepsy who continued phenytoin therapy [52]. Studies evaluating possible bone effects of other agents such as zonisamide, gabapentin, ethosuximide, and the newer AED lacosamide are still lacking. There were a number of limitations in our study that may underestimate the true compliance with osteoprotective behaviors. Data were collected from patients from one epilepsy clinic in New Brunswick, NJ, who were primarily seeing one epilepsy specialist who had an interest in bone health. Therefore, the results may be reflective of the patient population specific to an urban multiethnic region and may not be representative of patients with epilepsy in other regions. There is a potential for social desirability bias and recall bias resulting in patients having a tendency to report higher compliance in osteoprotective behaviors compared with an unbiased reporter keeping a current behavior diary. Patients who are not compliant with osteoprotective behaviors may have been more likely to decline participation in the study. Some behaviors or medications that also negatively impact bone were not collected, such as soda consumption or past exposure to depot medroxyprogesterone acetate injections. Some patients may not have

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recalled a complete medication history, leading to a falsely low exposure to AED reducers. Varying methods in obtaining answers to survey questions may have led to some variability. Data from our NJ patients with epilepsy were compared with those from the general NJ population in the NJBRFSS study to control for various regional effects on behavior. Our study was not designed to assess the effect of osteoprotective behaviors and AED history on DXA results. Future studies should assess whether AED selection and improved adherence to osteoprotective behaviors decrease the incidence of osteoporosis. 4.5. Patient engagement program After analysis of this study, we started an epilepsy support group at our community wellness center. This support group is completing the Project Healthy Bones program, which is a 24-week exercise and education program, created by the New Jersey Department of Human Services, Division of Aging Services (http://www.state.nj.us/ humanservices/doas/home/project.html). The exercises are designed to improve strength, flexibility, and balance. Education is provided to improve lifestyle changes to improve bone health. 5. Conclusion Patients with epilepsy have an increased risk of osteoporosis and fracture compared with the general population and need education about behaviors that protect bone. Evaluation with a DXA scan may be an important opportunity to identify patients with low BMD and to provide education regarding the benefits of calcium and vitamin D supplementation, appropriate diet, smoking cessation, weight-bearing exercise, and other risk factors for osteoporosis. A baseline DXA scan may be recommended in high-risk patients, such as long duration of AED therapy, refractory epilepsy, nonambulatory or institutionalized patients, low BMI, family history of osteoporosis, previous fracture history, exposure to bone-reducing AED (particularly phenytoin, phenobarbital, carbamazepine, and valproic acid), and/or intake of other bone-reducing medications. Moreover, time should be taken to discuss DXA scan results and what they mean with each patient. Clinicians should evaluate the benefit of switching patients to AEDs that are less likely to affect bone, minimize the use of agents that increase bone loss, and refer patients to an endocrinologist or an osteoporosis clinic to ensure sufficient patient education and follow up. Collaborate with local county public health agencies and other groups to develop programs that promote health self-management strategies aimed at preventing osteoporosis in patients with epilepsy. Abbreviations AED BMD BMI BRFSS DXA CHIS UMDNJ

antiepileptic drug bone mineral density body mass index Behavioral Risk Factor Surveillance System dual energy X-ray absorptiometry scan California Health Interview Survey University of Medicine and Dentistry of New Jersey

Disclosure The authors declare that they have no conflicts of interest. Acknowledgments This paper has been presented in abstract form at the 2011 American Epilepsy Society Meeting in Baltimore, Maryland. Interim data results were also presented in abstract form at the 2009 American College of

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