The Link Between Epilepsy and Osteoporosis: Understanding the Connection

People with epilepsy face many challenges beyond seizures themselves, including several potential comorbidities that can affect their long-term health. One significant but often overlooked association is the connection between epilepsy and osteoporosis—a condition characterised by reduced bone density that increases fracture risk. This relationship is multifaceted and deserves attention from both healthcare providers and patients.

The Prevalence of Bone Health Issues in Epilepsy

Research indicates that people with epilepsy have a 2-6 times higher risk of fractures compared to the general population. While seizure-related falls contribute to this statistic, reduced bone mineral density (BMD) is another critical factor. Studies show that up to 50% of people with chronic epilepsy may have reduced BMD, with approximately 20% meeting the diagnostic criteria for osteoporosis.

Understanding the Connection: Why Are People with Epilepsy at Risk?

The link between epilepsy and osteoporosis stems from several interconnected factors:

1. Anti-Seizure Medications (ASMs)

The most significant contributor to bone health problems in epilepsy is long-term use of certain anti-seizure medications:

• Enzyme-Inducing ASMs: Medications, such as carbamazepine, phenytoin, phenobarbital, and primidone accelerate vitamin D metabolism, leading to lower vitamin D levels and reduced calcium absorption. These drugs can also:
  • Increase bone turnover
  • Alter sex hormone levels that maintain bone health
  • Directly affect bone-forming cells (osteoblasts)
• Valproate: Though not enzyme-inducing, valproate may affect bone health through different mechanisms, including inhibition of osteoblast formation and potential effects on hormonal balance.
• Newer ASMs: Medications, including lamotrigine, levetiracetam, and lacosamide appear to have fewer effects on bone metabolism, though long-term studies are still emerging.

2. Reduced Physical Activity

Many people with epilepsy, particularly those with frequent or severe seizures, may limit physical activity due to:

• Fear of seizure-related injuries
• Overprotection by families or caregivers
• Restrictions on certain activities

This reduced weight-bearing exercise negatively impacts bone formation and maintenance, as bone density requires regular physical stress to remain healthy.

3. Vitamin D Deficiency

Vitamin D deficiency is common in epilepsy due to:

• Accelerated metabolism from enzyme-inducing ASMs
• Reduced sun exposure (some people with epilepsy may spend less time outdoors)
• Dietary insufficiency

4. Hormonal Factors

Epilepsy itself, particularly temporal lobe epilepsy, can affect the hypothalamic-pituitary axis, potentially leading to:

• Altered sex hormone levels
• Abnormal thyroid function
• Changes in growth hormone production

All these hormonal changes can negatively impact bone health independent of medication effects.

5. Direct Impact of Seizures

Some research suggests that seizure activity itself might affect bone metabolism through:

• Increased cortisol production during and after seizures
• Potential microtrauma to bones during convulsive seizures
• Inflammatory processes associated with seizure activity

Assessment and Screening Recommendations

Given these risks, bone health assessment should be part of routine care for people with epilepsy, particularly:

• Those taking enzyme-inducing ASMs for more than 2 years
• Anyone on long-term valproate therapy
• People with limited mobility or reduced physical activity
• Women with epilepsy, especially post-menopausal or with irregular menstrual cycles
• Anyone with additional risk factors for osteoporosis

Recommended screening includes:

• DEXA Scans: To measure bone mineral density, typically recommended every 2-5 years depending on risk factors
• Blood Tests: Calcium, vitamin D, parathyroid hormone, and markers of bone turnover
• Risk Assessment: Using tools like FRAX (Fracture Risk Assessment Tool) to estimate 10-year fracture risk

Prevention and Management Strategies

Medication Considerations

• Medication Choice: When possible, consider ASMs with less impact on bone metabolism for patients at high risk
• Minimising Polytherapy: Using the fewest needed medications at the lowest effective doses
• Transitioning Options: For patients with significant bone loss, discuss possible transition to bone-sparing ASMs if seizure control allows

Nutritional Interventions

• Calcium Supplementation: 1000-1500mg daily for adults with epilepsy on enzyme-inducing ASMs
• Vitamin D Supplementation: Often higher doses (1000-4000 IU daily) are needed for people on enzyme-inducing ASMs
• Balanced Diet: Rich in calcium, vitamin D, magnesium, vitamin K, and other nutrients supporting bone health

Lifestyle Modifications

• Weight-Bearing Exercise: Appropriately supervised physical activity programs
• Fall Prevention: Home safety assessments and balance training
• Smoking Cessation and Alcohol Moderation: Both significantly impact bone health

Pharmacological Treatments

For those diagnosed with osteoporosis or at high fracture risk:

• Bisphosphonates: First-line medications that slow bone breakdown
• Selective Estrogen Receptor Modulators: For postmenopausal women
• Denosumab: An alternative for those who cannot tolerate bisphosphonates
• Teriparatide: For severe cases of osteoporosis with existing fractures

Special Considerations for Different Age Groups

Children and Adolescents with Epilepsy

Bone health in young people with epilepsy deserves special attention as this is a critical period for bone mass acquisition:

• Regular monitoring of growth parameters
• Ensuring adequate calcium and vitamin D intake
• Encouraging age-appropriate physical activity
• Considering bone health when selecting ASMs for long-term use

Women with Epilepsy

Women face additional considerations:

• Hormonal fluctuations throughout the menstrual cycle may affect seizure frequency and bone health
• Pregnancy and breastfeeding create additional demands for calcium
• Early menopause is more common in women with epilepsy
• Postmenopausal bone loss may be accelerated

Older Adults with Epilepsy

Older adults with epilepsy face compounded risks:

• Age-related bone loss combined with epilepsy-related factors
• Higher fall risk, especially with certain ASMs that affect balance
• More frequent comorbidities affecting bone health
• Potential interactions between osteoporosis treatments and ASMs

The Role of Healthcare Providers

Effective management of bone health in epilepsy requires a multidisciplinary approach:

• Epileptologists/Neurologists: Regular consideration of bone health when selecting and monitoring ASM therapy
• Primary Care Providers: Routine bone health screening and preventive care
• Endocrinologists: Management of complex bone disorders and hormone-related issues
• Physiotherapists: Safe exercise programming
• Dietitians: Nutritional counselling for bone health
• Epilepsy Specialist Nurses: Education about bone health risks and preventive strategies

Conclusion

The connection between epilepsy and osteoporosis represents an important health consideration that requires proactive management. By understanding the risk factors and implementing preventive strategies, healthcare providers can help people with epilepsy maintain better bone health throughout their lives.

While seizure control remains the primary goal of epilepsy treatment, bone health should be considered as part of comprehensive care. Regular screening, appropriate supplementation, physical activity, and thoughtful medication selection can all contribute to reducing fracture risk and maintaining quality of life for people living with epilepsy.

People with epilepsy should feel empowered to discuss bone health with their healthcare providers and advocate for appropriate screening and preventive care as part of their overall epilepsy management plan.