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One of the two most widely prescribed anti-epileptic drugs may increase the risk of fractures in children with epilepsy, according to a Michigan Medicine study.
The article, published in Epilepsy, examined the effects of levetiracetam and oxcarbazepine, two common antiepileptics, on bone fragility in children aged four to 13 years. The researchers found that levetiracetam was not linked to fractures, but that oxcarbazepine was associated with a higher risk of fracture in children with epilepsy.
“Prior to this study, little research had been done on the impact of these two commonly prescribed drugs on bone fragility,” said Daniel Whitney, Ph.D., lead author of the article and assistant professor of physical medicine and rehabilitation center at Michigan Medicine. “These findings provide essential insight into the impact of two commonly prescribed drugs on children and adolescents during a critical period of bone development.”
During the pre to mid-puberty stage, several characteristics – such as genetics, bone structure and bone biology – combine to develop bone strength, which peaks in adulthood. The disruptions during these critical years can worsen and have lasting impacts on the musculoskeletal system.
The research team observed five-year fracture incidence rates between 561 children and adolescents with epilepsy and about 271,000 without epilepsy who were not taking anti-epileptic drugs. During this period, 12.8% of children on oxcarbazepine suffered a fracture, compared to 7.5% on levetiracetam and 8.2% without epilepsy.
These two drugs are commonly prescribed because they have relatively safer side effect profiles than some of the other anti-seizure drugs on offer, said Erin Fedak Romanowski, DO, corresponding author of the article and Clinical Assistant Professor of Pediatric Neurology at Michigan Medicine.
“Knowing that oxcarbazepine is associated with a higher fracture risk will allow clinicians to think more about the children for whom they prescribe the drug,” said Fedak Romanowski. “Some children will be at a higher risk of fracture than others initially; this is another factor to consider when assessing the complexity of which drugs to use for whom and when.
Whitney noted that the results did not mean that it is dangerous to prescribe oxcarbazepine, nor that all children with epilepsy should be on levetiracetam.
Many children and adolescents with epilepsy have associated neurodevelopmental disorders, such as cerebral palsy. This pediatric patient population is known to be at high risk for fractures, but side effects of levetiracetam can affect a child’s mental health, which is also a common comorbidity in children with neurodevelopmental disorders.
This concept is known as iatrogenesis, or medical problems that arise due to medical attention. Anti-epileptic drugs serve their eponymous purpose, but some can cause secondary complications like brittle bones and mood or behavior problems.
“Our goal for patients is ‘no seizures, no side effects’,” said Fedak Romanowski. “However, there is no perfect anti-seizure drug, and all of them have potential side effects,” she said. “But physicians can use all of this available information to take a personalized approach that optimizes the health outcomes for each patient. “
Whitney said her next step is a follow-up study to find out why oxcarbazepine is linked to increased fragility fractures during this unique time window. Then, the team concluded, they can assess whether children could benefit from additional therapies for bone fragility.
“As bone development has distinct periods that establish certain structural aspects, we are interested in studying whether certain drugs alter the biology required to form the structure of bone,” Whitney said. “If this is the case, maybe we can develop an adjunct treatment to counter these effects, so that children can benefit from reduced seizures without weakening the bones.”
Reference: Whitney DG, Caird MS, Hurvitz EA, Rajapakse CS, Romanowski EMF. Effect of levetiracetam and oxcarbazepine on the risk of fragility fracture at 4 years in children with prepubertal and pubertal epilepsy. Epilepsy. 2021; 62 (9): 2180-2189. do I: 10.1111 / epi.16998
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