Bone Health and Epilepsy: Are Your Bones Brittle?

Article Highlights

  • Long-term use of certain seizure medications can result in thinning of a person’s bones.
  • Reduced bone density results in osteopenia (mild bone density loss) or osteoporosis (severe bone density loss).
  • Osteoporosis can be very problematic for quality of life!
  • Low bone density predisposes people to bone fractures.
  • People with epilepsy are at higher risk for falls and other accidents that can cause bone breaks.
  • DEXA scan is an excellent way to determine a patient’s bone density- in order to diagnose if there is a problem with thinning of the bones.
  • Building healthy bones (treatments are tailored to the individual):
    • Exercise
    • Vitamin D
    • Calcium
    • Prescribed medication to build bone strength (biphosphonate therapy)

Introduction

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.

Bone Formation

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.

Mobility/Exercise

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.

Fractures

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!

Diagnosis

  1. Normal
  2. Osteopenia (mild bone density loss)
  3. Osteoporosis (severe bone density loss)

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).

Treatment

Prevention

  • Weight bearing exercise
  • Do not smoke cigarettes
  • Do not drink alcohol excessively
  • Take vitamin D and calcium

Osteopenia (Mild Bone Loss)

  • Take calcium and vitamin D
  • Depending on case, may consider changing AED—to reduce risk of developing osteoporosis (must be very cautious—do not want to risk serious seizures)

Osteoporosis (Severe Bone Loss)

  • Take calcium and vitamin D
  • Depending on case, may consider changing AED—to reduce risk of developing osteoporosis (must be very cautious—do not want to risk serious seizures)
  • Bisphosphonate therapy (= Fosamax, Actonel and Boniva)

Increases Risk for Fracture in Patients With Osteoporosis

  • Long-term AED use
  • Multiple AEDs
  • Older age
  • Female gender
  • Low body weight (<130 lbs)
  • Caucasian race
  • Recurrent falls
  • Reduced physical activity
  • Low calcium intake
  • Early menopause
  • Alcoholism
  • Tobacco use

Conclusions

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!

References

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.

James White, MD

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.

15 Responses to “Bone Health and Epilepsy: Are your bones brittle?”

Deb Thoennes August 15, 2011 at 6:12 am

In the past couple weeks, I’ve been searching for more information on this topic. Due to a lack of time, I’ve only skimmed the surface, but what I found was a wealth of information and studies that have been done connecting the 3A4 enzyme-inducing AED’s to the reduction of 25-OH D3, leading to bone loss. One particular article also stated in addition to decreased vitamin D levels, blood calcium levels were low, and parathyroid hormone levels were elevated. (Epilepsia 2006;47(S4),8 – “Changes in Vitamin D levels associated with enzyme inducing AED’s in male epilepsy patients”)………. I haven’t cited articles since college, so my apologies if I’ve done it incorrectly.

Would these tests be markers that could be checked early on in treatment, when appropriate, BEFORE decreased bone mass had a chance to take place? We’ve recently tested my husband’s Vitamin D levels, discovered it was low, and we are keeping an eye on it. Based on the information in this study, wouldn’t it pay to also check his serum calcium and parathyroid levels as well?

As my husband already has osteopenia (diagnosed in his early 30’s after about 10 years of AED use), this is an important topic for us, and I have many more observations and questions for you (and maybe a bone guru…?) I have a personal affinity for studying how things (foods, drugs, supplements) affect the body – Is there such a doctor that would specialize in BOTH epilepsy and nutritional deficiencies and/or disorders (such as bone loss) created by the use of AED’s? I’m finding some Epilepsia articles and studies that have been done correlating AED usage and nutritional deficiencies. For me, it would be nice to have professional confirmation (or contradiction) to some of the conclusions I draw on my own, or to answer questions I have related specifically to AED’s and nutrition.

The format you use to share information is great – very easy to follow, factual and interesting. It prompts me to say you could have been a writer, but I’m probably speaking for all of your patients when I say are we ever glad you are an epileptologist!

Reply By: James White, MD August 15, 2011 at 9:57 am

Thank you Deb for your great comments! It is obvious that you have reviewed the literature in tremendous detail. Also, in my opinion, you have summarized some of the most critical data on AEDs and bone density loss. I agree with all your comments. Enzyme induction is very likely an important mechanism for many patients.

However, (as you may already know) valproic acid (= Depakote) has been associated with osteoporosis and is not an enzyme inducer. Thus, although enzyme induction is likely an important factor for many patients, the mechanism is clearly incompletely understood. When we have a better understanding how AED use may result in bone loss, we can better identify patients who need treatment. Also, it will allow us to better determine which AEDs are more or less likely associated with bone loss—there are a multitude of important questions that need answers on this topic.
(I realize you may be aware of the above, but many folks are not).

As far as a specialist, there are experts who can provide consultation. Please call our clinic and I would be happy to make a recommendation.

Robyn April 24, 2012 at 11:15 am

Thank you Dr. White for informing me about this site. Of course with the meds I’m on, I’ve had osteoporosis for 5-6 years. I’m only 53 and I’m doing everything right except I need to lift weights for my arms and bring my heart rate up higher more often when walking, not just in the spring, summer and fall. Thanks again, I’m enjoyng this.

James White, MD April 24, 2012 at 12:17 pm

Thank you Robyn! We are going to continue to update this site with educational articles!

Andreas Heimler June 28, 2013 at 4:45 pm

My family members all the time say that I am wasting my time here at net, but I know
I am getting experience daily by reading thes nice articles or reviews.

Alice Giuliani September 11, 2014 at 4:52 pm

I am on two 100mg phenytoin sod daily in the morning, due to difficulty with sleeping. My recent bone density test definitely shows osteoporosis. I am 76 years old, walk my dog daily on hilly terrain, yoga classes weekly and bone strength supplement (NEWCHAPTER) & one glucosamine chondroitin.
What anti-seizure medication do you recommend. Dr. Pack’s one year study showed phenytoin patients showed significant bone loss. Your advice is greatly appreciated.
If body weight is of any significance, I am 100 lbs. & 5’1 1/2 tall.

John T. Ward September 19, 2014 at 9:00 pm

Before you agree to using Tegretol for your epilepsy condition, make sure that the people who agreed to watch over you during this trial do not believe “doctors know everything”. (A survey indicates that at least twenty percent of mothers believe this.)

Note: When my right hip shattered after using Tegretol about one year, my doctor (who the Epilepsy Foundation advised me to see) lowered the Tegretol and, after several months, I could begin to think again. The neurologist then attempted to kill me and brought me within “two days” (Truman Medical Center in Kansas City, Missouri) of death with Dilantin (blood level 36.6).

Greg Marlow October 24, 2014 at 4:58 am

It may be that bone loss is what is alleviating epileptic symptoms. The extra calcium released from the bone raises blood calcium levels which then lowers neuron excitability. AEDs accelerate the release but the body has its own mechanism for releasing calcium from the bone when blood levels are too low.

Greg Marlow October 24, 2014 at 4:58 am

It may be that bone loss is what is alleviating epileptic symptoms. The extra calcium released from the bone raises blood calcium levels which then lowers neuron excitability. AEDs accelerate the release but the body has its own mechanism for releasing calcium from the bone when blood levels are too low. This may explain the association of bone loss and epilepsy in general.

Greg Marlow October 24, 2014 at 4:58 am

It may be that bone loss is how some AEDs get their effectiveness. Bone loss raises blood calcium levels and higher calcium levels lower neuron excitability.

Tom December 15, 2014 at 9:35 am

Hello,
I have had epilepsy and been on medication for roughly 12 years now. I currently take Tegretol XR and Kepra. I recently had to have surgery on my knee due to a cartilage issue (a large chunk of articular cartilage broke free from my femur). This was due to possible overuse from running marathons and training.
After 2 surgeries and a Staph infection in the knee the doctors now think that there is underlying bone issues with the femur (possible bone degeneration). Could this have anyting to do with prolonged use of the AE medications?
Thank you,
Tom

Theresa Bomkamp July 31, 2016 at 10:07 am

Hello….well i have been on phenobarbital since 1960. That was when I was first diagnosed with epilepsy at the age of six. I was told I would grow out of it. Through the years of having six children, I had one within 4wks of delivery of them except the first one. My first grand mal I was 13, 5 months before my periods began.My last child was born in 1996, my seizure was split in half and finally out of my system a month later and I began taking phenobarbital and dilantin then. My current dr wanted me to see a neurologist and this neurologist determined I have osteopenia and put me on calcium and vitamin d. I will have a bone scan in a few days. I have not had any seizures since december 1996. It is through this website, that I learned anti seizure meds can cause bone loss, the osteopenia I have been dx’d with. I wish the doctors had told me. I am almost 62 now, working as a custodian p/t and about to retire as I am feeling much older than I am. I broke my first and only bone 29 mos ago, slipping on black ice. I wonder now if that same ankle, which I have badly sprained over the yrs, wasn’t my first clue.

M. Robin Stenkamp September 30, 2016 at 8:07 pm

After 43 years on multiple anticonvulsants your article was full of information I knew and reenforced what I have learned and made me feel good about charging ahead with exercise and vitamins and also pray the DEA pushes for some research on cbd. CBD might help many of us. It’s chemical composition is very different than anticonvulsants that are hard on our bones! Thank you.

Pamela Lillyblad September 16, 2018 at 2:47 pm

I am writing for my son a 33 year old with epilepsy. He has either osteopenia or Osteoporosis from Depakote. We found out because my son went to a chiropractor who had the sense to do a bone density test before he went cracking my sons back. I had to tell Barrow’s about it. They changed his meds. He takes calcium and d3 now. He had epilepsy surgery amygdalohippocampectomy due to a head injury at age 5. That aside. He has a VNS implant which is turned off because it makes his GI system upset. Even thought it is turned off it is still the cause of GERD, constant burping…He has had a whole GI workup and they all concur at this GI practice that the stimulator is the cause. Barrow’s will not agree with this because they say after the vns is in 10 years the scar tissue makes it dangerous to remove. We complained 10 years ago but they still would not take it out. I have read the risks. I understand that Dr. Bingaman at Cleveland Clinic takes VNS out. Have you ever heard of VNS causing GI problems for someone that was so bad it was affecting appetite, causing burping, indigestion? Just reaching out for answers to see if anyone else in their practice has seen this problem. I am asking Barrows to get my son to Cleveland Clinic and asking them to call Dr. Bingaman. Just want to know if you have heard of this problem.
Thanks,
Pam Lillyblad

[News] Epilepsy drugs increase risk of fractures and falls – Epilepsy Forum July 8, 2012 at 4:44 pm

been as clearly shown to be associated with bone density loss, but fewer studies are available. Bone Health and Epilepsy: Are your bones brittle? __________________ “It’s no longer a question of staying healthy. It’s a question of finding