By: Hiya Shah
Epilepsy and Bone Health
Bones are an integral part of the human body, supporting us every day, doing everything (literally). From organ protection to mineral storage, bones do a lot. Unfortunately, bone health is often overlooked. About half of all Americans over age 50 have weak bones, as stated by Dr. Campbell (2024).
Even more susceptible are patients with epilepsy to low bone health, being at a 2-6 times greater risk of fracturing bones (Svalheim et al., 2011).
With about 50 million individuals diagnosed with epilepsy globally, it is the most common neurological disease, making bone health an important topic (Andersen & Jørgensen, 2022).
Disclaimer: Many earlier studies use the term antiepileptic drugs (AEDs) to describe medications used to control seizures. However, more recent literature has adopted the term antiseizure medications (ASMs) to provide greater accuracy. For consistency, this article will use the term ASM.
Sheth (2004) outlines how children and adolescents are at crucial periods of bone development in which key minerals are being deposited into the bone matrix, which is termed skeletal mineralization. Chronic conditions such as childhood-onset epilepsy adversely impact mineralization during development, impairing bone health and resulting in lower peak bone mass. Epilepsy affects bone development in ways you may not expect, making it especially important to be aware of low bone health risk factors.
Svalheim et al. (2011) provide a list of risk factors causing low bone health in adults:
Female gender
Caucasian or Asian ethnicity
Sedentary lifestyle
Null parity
Early menopause/postmenopausal status
Increasing age
High caffeine intake
Physical inactivity
Smoking
Excessive alcohol intake
Low body mass index
Inadequate sun exposure
Some medications (e.g., glucocorticoids, heparin, aluminum-containing antacids, lithium, some chemotherapeutics, selective serotonin reuptake inhibitors, and antiepileptic drugs)
Some diseases (e.g. intestinal diseases with malabsorption, liver disease, kidney disease, anorexia nervosa, hyperthyroidism, hyperparathyroidism, and Cushing’s syndrome)
Out of these, “antiepileptic drugs” (now known as antiseizure medications) are the main cause of low bone marrow density within epileptic individuals. An additional cause is limitations on physical activity due to seizure risk (Sheth, 2004). Consequently, a skeletal disorder, osteoporosis, affecting 11%-31% of epileptic individuals, has been linked to ASM consumption over a long period of time (Andersen & Jørgensen, 2022).
Svalheim et al. (2011) underline the common explanation of the relation between impaired bone health and ASMs. Vitamin D is essential for calcium absorption, and low vitamin D leads to hypocalcemia. The body maintains calcium levels by pulling calcium from the bones, thus decreasing bone mineral density, leading to a higher risk of fractures and osteoporosis. Why does this matter? Because vitamin D is broken down by liver enzymes, the activity of which is increased by many ASMs. Furthermore, some ASMs directly impair bone-building cells (osteoblasts) functioning while activating bone-breaking cells (osteoclasts; Andersen & Jørgensen, 2022).
Andersen and Jørgensen (2022) provide a visual of the more diverse ways epilepsy may lead to fractures:
Within ASMs, the most common are:
Phenytoin
Phenobarbital
Primidone
Carbamazepine
Valproate
Out of these, phenytoin, primidone, and phenobarbital are the most notorious for causing decreased BMD, with reports as early as the 1960s detailing the use of these medications as a cause of bone disease. Carbamazepine, while providing similar effects to the former for enzyme activity, has earlier studies reporting conflicting claims (Pack & Morrell, 2004). Newer research has confirmed that carbamazepine adversely impacts BMD as well. While valproate mechanisms differ from the prior, it still decreases BMD and lowers bone health through effects on bone cells. As Andersen and Jørgensen (2022) state, “there is limited data on whether and how the newer ASM (lamotrigine, lacosamide, eslicarbamazepine, zonisamide, and perampanel) influence bone health.”
Andersen & Jørgensen (2022) state that, currently, a primary measure of bone health is measuring vitamin D levels. Thus, prevention and treatment strategies include prescribing vitamin D and calcium supplements and suggesting regular physical activity for those taking AEDs. While not many studies have been conducted regarding treatment strategies for low BMD associated with ASMs, a study highlighted by Pack (2011) finds overwhelming support for vitamin D in increasing BMD and bone health.
Offering bone mineral density measurement tests (using a dual-energy X-ray absorptiometry, “DXA”, scan) for any patients with risk factors is also very beneficial. BMD scores are T-scores with the reference range of young female Caucasians. According to the WHO, osteoporosis has a site-specific T-score of less than or equal to −2.5 SD…
≤ −2.5 SD: Osteoporosis
-2.5 ≤ SD ≤ -1.0: Osteopenia (low BMD)
-1.0 SD: Normal BMD
(Andersen & Jørgensen, 2022)
Usually, awareness is also a prevention strategy. This includes dietary intake changes to increase bone health. Public awareness initiatives such as “public health education programmes, community projects, websites, and nutritional and fitness guidelines” are also in place to promote lifestyle changes (Rizzoli, 2014). Awareness of possessing low BMD also leads to increased positive lifestyle changes. Similarly, Rizzoli (2014) highlights how educating doctors about tools such as the Fracture Risk Assessment (FRAX) leads to an increased likelihood of them assessing patients’ fracture risk and promoting positive lifestyle changes.
To summarize, Sheth and Harden (2007) outline a management strategy plan for epileptic individuals with low BMD:
Lifestyle changes
Calcium and vitamin D
Seizure control
AED evaluation
Follow-up BMD test
To conclude, while many pharmaceuticals aid the seizures that come with epilepsy, they result in adverse side effects. Low bone mineral density, while plaguing a large population, is not discussed nearly enough. With more awareness, some supplements, and changes in lifestyle, its effects can be radically subdued.
References
Andersen, N. B., & Jørgensen, N. R. (2022). Impaired bone health as a co-morbidity of epilepsy. Best Practice & Research Clinical Rheumatology, 36(3), 101755. https://doi.org/10.1016/j.berh.2022.101755
Campbell , B. J. (2024). Bone health basics . OrthoInfo. https://www.orthoinfo.org/en/staying-healthy/bone-health-basics/
Pack, A. M. (2011). Treatment of epilepsy to optimize bone health. Current Treatment Options in Neurology, 13(4), 346–354. https://doi.org/10.1007/s11940-011-0133-x
Pack, A. M., & Morrell, M. J. (2004). Epilepsy and bone health in adults. Epilepsy & Behavior, 5, 24–29. https://doi.org/10.1016/j.yebeh.2003.11.029
Rizzoli, R. (2014). Nutritional aspects of bone health. Best Practice & Research Clinical Endocrinology & Metabolism, 28(6), 795–808. https://doi.org/10.1016/j.beem.2014.08.003
Sheth, R. D. (2004). Bone health in pediatric epilepsy. Epilepsy & Behavior, 5, 30–35. https://doi.org/10.1016/j.yebeh.2003.11.025
Sheth, R. D., & Harden, C. L. (2007). Screening for bone health in epilepsy. Epilepsia, 48(s9), 39–41. https://doi.org/10.1111/j.1528-1167.2007.01401.x
Svalheim, S., Røste, L. S., Nakken, K. O., & Taubøll, E. (2011). Bone health in adults with epilepsy: Bone health and epilepsy. Acta Neurologica Scandinavica, 124, 89–95. https://doi.org/10.1111/j.1600-0404.2011.01551.x
