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It has been known for decades that antiepileptic drugs (AEDs) are associated with bone density loss. Reduced bone density results in osteopenia (mild bone density loss) or osteoporosis (severe bone density loss). Low bone density predisposes people to fractures. Fractures usually involve the hip, spine or forearm. Bone health has recently become a hot-topic in the epilepsy community because much more is now known about the devastating impact of bone loss on quality of life. In the general population, approximately 40% of women and 13% of men older than 50 years will develop a fracture associated with reduced bone density. Patients with hip fractures far too commonly go from independent living to requiring nursing home placement. In selected populations, of those who develop a hip fracture, 20-30% will die within one year. The dramatic effect that osteoporosis has on quality of life has been a wake-up call for better diagnosis and treatment of this disorder.
This article reviews bone health issues pertinent to patients with epilepsy.
A brief review on bone formation will help the reader understand important issues in this article. The most critical time for bone development occurs early in life. Bone density builds during childhood and peaks at approximately age 20 years. Between 20 and 40 years of age, bones remain at a fairly constant level of strength. After age 40, bone density gradually declines. As people reach older age, bones that are weakened by declining bone density may become easily broken with even minor falls.
Factors that are important in developing good bone strength include adequate calcium, vitamin D and exercise.
BONE HEALTH ISSUES
AEDs and bone loss
Long-term use of AEDs has been clearly associated with the development of osteopenia and osteoporosis. The use of more than one AED increases the risk. It is not clear how long it will take to develop bone density problems in patients taking AEDs. Once a patient has been on an AED for approximately 5 years, physicians may consider testing bone density. Certain AEDs have clear studies indicating an association with osteoporosis. These AEDs include phenytoin (= Dilantin), carbamazepine (=Tegretol, Carbatrol), valproic acid (= Depakote) and phenobarbital. The newer AEDs have not been as clearly shown to be associated with bone density loss, but fewer studies are available.
The question “How do AEDs cause osteoporosis?” is currently a very active area of research. One possibility is by reducing vitamin D. Vitamin D is important for the normal absorption of calcium. If vitamin D is deficient, then calcium is not absorbed normally. Low calcium results in weak bones. Certain AEDs (phenytoin (= Dilantin), carbamazepine (=Tegretol, Carbatrol) and Phenobarbital) increase the metabolic rate of the liver. This increased metabolic rate causes a reduction in vitamin D. Although low vitamin D may be an important cause of osteoporosis in patients taking AEDs, other reasons are also hypothesized. The current thinking is that reduced vitamin D does not explain all cases of osteoporosis, so other mechanisms must be important.
Adequate bone formation early in life is critical for strong bones later in life. AEDs have the potential to prevent bones from reaching a normal peak density by age 20 years. If patients do not have strong bones by early adulthood, then the gradual decline over the years may result in low bone density at a relatively early age. Some patients can develop osteoporosis as young adults or even earlier! Also, AEDs started in adulthood can accelerate the loss of bone strength. Again, this can set a patient up for weakened bones.
Bones get stronger with hard work! The forceful pounding of the pavement, jumping, running and lifting the weight of their owner leads to good strong bones. If patients are having limitations in mobility, then bones may have difficulty reaching their full strength. For example, patients who are in a wheelchair or have significant weakness in their arms and/or legs may not be able to adequately exercise to achieve normal bone density. Some people may have chronic diseases or other reasons that prevent them from being adequately mobile. Such patients are at higher risk for developing osteoporosis.
Exercise has been demonstrated to be beneficial for bone density. For example, women who performed weight-bearing exercise for 30 minutes every day had a 4% increase in spine bone density. In contrast, the controls (who did not exercise significantly) lost 3% of bone density. Thus, exercise is likely a good way to prevent and treat bone density loss.
Patients with epilepsy have 2-6 times the rate of breaking bones compared to the general population. There are multiple reasons for the increased risk of fracture in those with epilepsy. One reason is that patients with epilepsy are at increased risk for accidents. Patients with epilepsy may be at high risk for falling because of seizure activity. Seizures can result in some truly terrible accidents. Patients may not be able to brace a fall because of the seizure activity. The seizures may occur at very unfortunate times—in the shower, walking down stairs, while driving or up on a ladder. Also, patients are on medications which can make them walk in a very unsteady fashion. Patients know this issue well. Patients are often asked during a clinic appointment to walk with one foot in front of the other (like the police officer’s test!). Patients often have difficulty with this because of their AEDs. The poor balance can result in falls—especially if the patient is walking on an uneven surface, when it is dark or icy.
Another reason for the increased fractures in patients with epilepsy is the reduced bone density noted in this population. The weaker bones do not handle falls well—bones can break even with minor falls or injuries. To say this is frustrating is an understatement!
Bone density falls into one of three categories:
The gold-standard test for testing bone density is the dual-energy x-ray aborptiometry scan. Do not try to remember this long term for this test. Just remember DEXA scan. The DEXA scan is a relatively easy test for a patient to go through. It will reliably diagnose problems with bone strength. There is a very strong correlation between reduced bone density (weak bones) and fractures.
It is not clear precisely when to obtain a bone density on an individual patient. It is often recommended that after 5 years of AED use, a bone density should be considered. Shorter time frames may be appropriate for certain high risk groups (such as elderly women and those who are wheelchair bound).
Osteopenia (mild bone loss)
Osteoporosis (severe bone loss)
INCREASES RISK FOR FRACTURE IN PATIENTS WITH OSTEOPOROSIS:
Patients who have been taking seizure medications for several years need to be aware of the possibility of bone density loss. Bone density loss can be a major problem for quality of life—leading to possible osteoporosis. Health care providers and epilepsy patients need to: 1) discuss this issue in detail; 2) decide on whether or not testing for bone density is indicated; 3) use preventative measures to improve bone health (exercise, for example) and 4) if bone loss is a problem, then provide the optimal treatment. The real key is tailoring the prevention and treatment plan to the individual patient to obtain the best possible outcome!
Sheth RD, Harden CL. Screening for bone health in epilepsy. Epilepsia 2007;48 (suppl):39-41.
Pack AM. The association between antiepileptic drugs and bone disease. Epilepsy Currents 2003;3:91-95.
Sheth RD. Bone health in epilepsy. Epilepsia 2002;43:1453-1454.
Bone mass graph: http://www2.kumc.edu/coa/images/Reynolds/bone-mass-graph.gif
Dr. White has been practicing as a full-time epileptologist since 1999. His practice focuses on optimizing the diagnosis and treatment of patients with seizure disorders. Dr. White’s special interests include patient education, improving the side-effect profile of seizure medications, and epilepsy surgery.