Researchers studied 476 people with epilepsy to understand how seizure medications affect bone health. They found that after taking these medications for more than 2 years, certain bone markers change in ways that suggest bones become weaker. The study identified specific medications and combinations that have the biggest impact on bones, and discovered that inflammation in the body may play a role in these changes. These findings could help doctors catch bone problems early in patients taking long-term seizure medications.

The Quick Take

  • What they studied: How seizure medications affect bone health and bone strength over time in people with epilepsy
  • Who participated: 476 people with epilepsy, divided into groups based on how long they had been taking seizure medications (from no medication to more than 10 years)
  • Key finding: After taking seizure medications for more than 2 years, people showed changes in bone markers that suggest their bones are becoming weaker. The longer someone takes these medications, the more pronounced these changes become.
  • What it means for you: If you take seizure medications long-term, your doctor may want to monitor your bone health more closely. This doesn’t mean you should stop your medication—seizure control is crucial—but regular bone health check-ups may become more important as you continue treatment.

The Research Details

This was a cross-sectional study, which means researchers looked at a large group of people with epilepsy at one point in time and compared different subgroups. They divided the 476 participants into groups based on how long they had been taking seizure medications: those not taking any medication, those taking medication for less than 2 years, those taking it for 2-10 years, and those taking it for more than 10 years. The researchers measured specific substances in the blood that indicate how active bone cells are and how quickly bones are breaking down and being rebuilt. They used advanced computer analysis (called machine learning) to figure out which medications and combinations had the biggest effects on bone health. They also looked at whether inflammation in the body might explain why bones are affected.

Understanding how seizure medications affect bones is important because people with epilepsy already have a higher risk of weak bones and fractures. By identifying early warning signs through blood tests, doctors could potentially catch bone problems before they become serious. This study helps explain the mechanism—how and why these medications affect bones—which is the first step toward developing better prevention strategies.

This study included a reasonably large sample size (476 people), which makes the findings more reliable. The researchers used advanced statistical methods to account for other factors that might affect bone health. However, because this is a cross-sectional study (a snapshot in time rather than following people over years), we can’t be completely certain about cause-and-effect relationships. The study also included some follow-up data over 2 years, which strengthens the findings. The research was published in a peer-reviewed journal, meaning other experts reviewed it before publication.

What the Results Show

The main finding was that people taking seizure medications for more than 2 years showed changes in bone markers that suggest their bones are breaking down faster than they’re being rebuilt. Specifically, a marker called the β-CTX/OC ratio decreased significantly after 2 years of medication use. This ratio is important because it shows the balance between bone breakdown and bone formation. When this ratio drops, it suggests that bone-breaking cells (osteoclasts) are being slowed down, but bone-building cells (osteoblasts) haven’t yet been affected. However, after more than 10 years of medication use, another marker called P1NP (which shows bone formation) also declined, suggesting that bone-building cells eventually start to slow down too. This pattern suggests that bone problems develop in stages: first, the balance shifts toward less breakdown, but eventually, the body’s ability to build new bone decreases.

The study identified that certain seizure medications have stronger effects on bones than others. Valproic acid and oxcarbazepine appeared to have the most significant impact. When people took multiple seizure medications together (polytherapy), the effect on bones was stronger than when taking just one medication (monotherapy). Interestingly, the combination of levetiracetam with either valproic acid or oxcarbazepine had particularly pronounced effects. The research also found that inflammation markers in the blood—specifically the ratio of certain white blood cells—appeared to explain some of the bone changes, suggesting that inflammation is part of the mechanism by which these medications affect bone health.

Previous research has shown that people with epilepsy have higher rates of bone loss and fractures, but this study provides new insight into the timeline and mechanism. Earlier studies suggested that seizure medications generally weaken bones, but this research shows that the process happens in stages and that different medications have different effects. The finding that inflammation may play a role is relatively new and could open up new ways to protect bone health in people taking these medications. This study also identifies specific biomarkers (the β-CTX/OC ratio) that could be used for early detection, which is an advance over previous research.

This study has several important limitations to consider. First, it’s a cross-sectional study, which means we’re looking at different people at different stages of treatment rather than following the same people over time. This makes it harder to prove that the medications directly cause the bone changes. Second, the study didn’t include information about other important factors that affect bone health, such as exercise, calcium and vitamin D intake, or family history of osteoporosis. Third, the study measured bone markers in blood rather than actual bone density, so we don’t know for certain how much weaker the bones actually become. Finally, the reasons why people started or stopped taking certain medications weren’t fully explored, which could affect the results.

The Bottom Line

People with epilepsy taking seizure medications should discuss bone health monitoring with their doctor, especially if they’ve been on medication for more than 2 years. This might include regular blood tests to check vitamin D levels and bone markers, and possibly bone density scans (DEXA scans) at regular intervals. Maintaining adequate calcium and vitamin D intake, doing weight-bearing exercise, and avoiding smoking and excessive alcohol are important for all people but especially for those on long-term seizure medications. However, it’s crucial to continue taking seizure medications as prescribed—the benefits of seizure control far outweigh the potential bone risks, and stopping medication without medical guidance could be dangerous. These recommendations are based on moderate evidence from this study combined with existing knowledge about bone health.

People with epilepsy who have been taking seizure medications for more than 2 years should pay special attention to bone health. This is especially important for women after menopause, older adults, and anyone with a family history of osteoporosis. People taking valproic acid or oxcarbazepine, or those taking multiple seizure medications, may want to be particularly vigilant. However, these findings don’t apply to people taking seizure medications short-term or those not yet on medication. People without epilepsy don’t need to worry about these effects.

Bone changes appear to begin after 2 years of seizure medication use, based on the markers measured in this study. However, actual bone weakening and fracture risk may take much longer to develop. The study followed people for 2 years and saw continued changes during that period, but we don’t know exactly how long it takes for bone problems to become clinically significant. This is why regular monitoring is important—catching changes early allows for intervention before serious bone loss occurs.

Want to Apply This Research?

  • Track seizure medication use with dates started and any changes in medications. Log annual bone health check-ups including vitamin D levels and any bone density test results. Record calcium and vitamin D intake daily, and note any falls or bone pain that might indicate bone fragility.
  • Set reminders to take calcium and vitamin D supplements if recommended by your doctor. Schedule regular exercise (weight-bearing activities like walking or strength training) at least 3-4 times per week. Create alerts for annual bone health screening appointments. Log any new seizure medications or dosage changes to track correlation with bone health markers.
  • Create a yearly bone health dashboard showing trends in vitamin D levels and bone markers over time. Set up notifications for annual doctor visits focused on bone health assessment. Track medication changes and correlate with any bone health test results. Monitor for any new symptoms like bone pain, increased fractures, or loss of height, which could indicate accelerating bone loss.

This research summary is for educational purposes only and should not replace professional medical advice. People with epilepsy should not stop or change their seizure medications based on this information, as seizure control is critical for safety. If you have concerns about how your seizure medications might affect your bones, discuss them with your neurologist or primary care doctor. They can assess your individual risk factors and recommend appropriate monitoring or preventive measures. This study shows associations between seizure medications and bone changes, but does not prove that all people taking these medications will develop bone problems. Individual responses vary based on genetics, lifestyle, and other health factors.