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Anti-epileptic drugs and osteoporosis risk

Some anti-epileptic drugs can secretly weaken your bones—here’s what you need to know.
close up of pills

Anti-epileptic drugs (AEDs), also known as anticonvulsants, are medications used to prevent or control seizures in people with epilepsy. They work by targeting different mechanisms in the brain to stabilise electrical activity and prevent the excessive, abnormal firing of neurons that leads to seizures.

Anti-epileptic drugs (AEDs), also known as anticonvulsants, are medications used to prevent or control seizures in people with epilepsy. They work by targeting different mechanisms in the brain to stabilise electrical activity and prevent the excessive, abnormal firing of neurons that leads to seizures.

Some AEDs can contribute to osteoporosis through several mechanisms that affect bone metabolism. Here’s how:

 

1. Vitamin D deficiency

Enzyme induction in the liver: Some AEDs, especially those that are enzyme inducers (e.g., phenytoin, phenobarbital, carbamazepine, and primidone), increase the activity of liver enzymes that metabolise vitamin D1. This leads to lower serum levels of active vitamin D, impairing calcium absorption from the intestines.

Reduced calcium absorption: Without sufficient vitamin D, the intestines absorb less calcium, which results in hypocalcaemia2. To compensate, the body increases parathyroid hormone (PTH) levels, which releases calcium from bones, leading to bone resorption3.

 

2. Direct effects on bone cells

AEDs may have a direct toxic effect on osteoblasts (bone-forming cells), reducing bone formation4,5.

Some AEDs, like valproic acid, can increase osteoclast activity (bone resorption), which further contributes to bone loss6.

woman sat at table taking medication

Some AEDs can contribute to osteoporosis through several mechanisms that affect bone metabolism. Here’s how:

 

1. Vitamin D deficiency

Enzyme induction in the liver: Some AEDs, especially those that are enzyme inducers (e.g., phenytoin, phenobarbital, carbamazepine, and primidone), increase the activity of liver enzymes that metabolise vitamin D1. This leads to lower serum levels of active vitamin D, impairing calcium absorption from the intestines.

Reduced calcium absorption: Without sufficient vitamin D, the intestines absorb less calcium, which results in hypocalcaemia2. To compensate, the body increases parathyroid hormone (PTH) levels, which releases calcium from bones, leading to bone resorption3.

 

2. Direct effects on bone cells

AEDs may have a direct toxic effect on osteoblasts (bone-forming cells), reducing bone formation4,5.

Some AEDs, like valproic acid, can increase osteoclast activity (bone resorption), which further contributes to bone loss6.

woman sat at table taking medication
doctor writing on a clip board

3. Hormonal imbalances

AEDs can affect sex hormones such as estrogen7 and testosterone8, both of which play crucial roles in maintaining bone density. Decreased levels of these hormones may lead to accelerated bone loss, especially in postmenopausal women or older men.

 

4. Increased fall risk

AEDs can cause sedation, dizziness, blurred vision and ataxia, which increase the risk of falls and fractures9, especially in older adults10.

 

5. Chronic use and long-term impact

Long-term use of AEDs is a key risk factor for osteoporosis. Bone mineral density tends to decrease over time, making individuals on long-term AED therapy more susceptible to osteopenia and osteoporosis11.

doctor writing on a clip board

3. Hormonal imbalances

AEDs can affect sex hormones such as estrogen7 and testosterone8, both of which play crucial roles in maintaining bone density. Decreased levels of these hormones may lead to accelerated bone loss, especially in postmenopausal women or older men.

 

4. Increased fall risk

AEDs can cause sedation, dizziness, blurred vision and ataxia, which increase the risk of falls and fractures9, especially in older adults10.

 

5. Chronic use and long-term impact

Long-term use of AEDs is a key risk factor for osteoporosis. Bone mineral density tends to decrease over time, making individuals on long-term AED therapy more susceptible to osteopenia and osteoporosis11.

Prevention and management

This link between AEDs and osteoporosis underscores the importance of proactive bone health management in epilepsy patients. There are several steps that can be taken to protect bone health when taking AEDs:

  • Calcium and Vitamin D supplementation: Recommended for patients on long-term AED therapy.
  • Bone density monitoring: Regular bone scans (DEXA or REMS) to monitor bone health.
  • Lifestyle modifications: Weight-bearing exercises, avoiding smoking and excessive alcohol.
  • Alternative AEDs: In some cases, non-enzyme-inducing AEDs (e.g. lamotrigine, levetiracetam) may be considered if bone health is a concern and these medications are suitable for the individual.
  • Low-intensity Vibration therapy with the Marodyne LiV: A natural therapy that boosts bone density, with no known side effects or contraindications with AEDs.

 

vitamin D supplement

Prevention and management

This link between AEDs and osteoporosis underscores the importance of proactive bone health management in epilepsy patients. There are several steps that can be taken to protect bone health when taking AEDs:

  • Calcium and Vitamin D supplementation: Recommended for patients on long-term AED therapy.
  • Bone density monitoring: Regular bone scans (DEXA or REMS) to monitor bone health.
  • Lifestyle modifications: Weight-bearing exercises, avoiding smoking and excessive alcohol.
  • Alternative AEDs: In some cases, non-enzyme-inducing AEDs (e.g. lamotrigine, levetiracetam) may be considered if bone health is a concern and these medications are suitable for the individual.
  • Low-intensity Vibration therapy with the Marodyne LiV: A natural therapy that boosts bone density, with no known side effects or contraindications with AEDs.

 

vitamin D supplement

References

  1. Saket S, et al. (2021). How Antiepileptics May Change the Serum Level of Vitamin D, Calcium, and Phosphorus in Children with Epilepsy. Iran J Child Neurol. 15(1):19-27.
  2. Richens A, Rowe DJ. (1970). Disturbance of calcium metabolism by anticonvulsant drugs. Br Med J. 4(5727):73-6.
  3. Sharma T, et al. (2017) Carbamazepine induced secondary hyperparathyroidism: A rare clinical entity.  International Journal of Comprehensive and Advanced Pharmacology, 2(2):68-69.
  4. Andress DL, Ozuna J, Tirschwell D, et al. (2002). Antiepileptic Drug–Induced Bone Loss in Young Male Patients Who Have Seizures. Arch Neurol. 59(5):781–786.
  5. Pitetzis DA, et al. (2017). The effect of VPA on bone: From clinical studies to cell cultures—The molecular mechanisms revisited. Seizure. 48:36-43.
  6. Xie, X., Cheng, P., Hu, L. et al. (2024). Bone-targeting engineered small extracellular vesicles carrying anti-miR-6359-CGGGAGC prevent valproic acid-induced bone loss. Sig Transduct Target Ther 9, 24.
  7. Svalheim S, et al. (2015). Interactions between antiepileptic drugs and hormones. Seizure. 28:12-17.
  8. Najafi MR, et al. (2012). Effects of antiepileptic drugs on sexual function and reproductive hormones of male epileptic patients. Iran J Neurol. 11(2):37-41.
  9. Ahmad BS, et al. (2012). Falls and fractures in patients chronically treated with antiepileptic drugs. Neurology, 79(2):145-151.
  10. Maximos M, Chang F, Patel T. (2017). Risk of falls associated with antiepileptic drug use in ambulatory elderly populations: A systematic review. Can Pharm J (Ott). 150(2):101-111.
  11. LoPinto-Khoury C. (2022). Long-Term Effects of Antiseizure Medications. Semin Neurol. 42(5):583-593.

References

  1. Saket S, et al. (2021). How Antiepileptics May Change the Serum Level of Vitamin D, Calcium, and Phosphorus in Children with Epilepsy. Iran J Child Neurol. 15(1):19-27.
  2. Richens A, Rowe DJ. (1970). Disturbance of calcium metabolism by anticonvulsant drugs. Br Med J. 4(5727):73-6.
  3. Sharma T, et al. (2017) Carbamazepine induced secondary hyperparathyroidism: A rare clinical entity.  International Journal of Comprehensive and Advanced Pharmacology, 2(2):68-69.
  4. Andress DL, Ozuna J, Tirschwell D, et al. (2002). Antiepileptic Drug–Induced Bone Loss in Young Male Patients Who Have Seizures. Arch Neurol. 59(5):781–786.
  5. Pitetzis DA, et al. (2017). The effect of VPA on bone: From clinical studies to cell cultures—The molecular mechanisms revisited. Seizure. 48:36-43.
  6. Xie, X., Cheng, P., Hu, L. et al. (2024). Bone-targeting engineered small extracellular vesicles carrying anti-miR-6359-CGGGAGC prevent valproic acid-induced bone loss. Sig Transduct Target Ther 9, 24.
  7. Svalheim S, et al. (2015). Interactions between antiepileptic drugs and hormones. Seizure. 28:12-17.
  8. Najafi MR, et al. (2012). Effects of antiepileptic drugs on sexual function and reproductive hormones of male epileptic patients. Iran J Neurol. 11(2):37-41.
  9. Ahmad BS, et al. (2012). Falls and fractures in patients chronically treated with antiepileptic drugs. Neurology, 79(2):145-151.
  10. Maximos M, Chang F, Patel T. (2017). Risk of falls associated with antiepileptic drug use in ambulatory elderly populations: A systematic review. Can Pharm J (Ott). 150(2):101-111.
  11. LoPinto-Khoury C. (2022). Long-Term Effects of Antiseizure Medications. Semin Neurol. 42(5):583-593.