Mallory Kirkland '14
Hometown: Guntersville, Alabama
Senior Study Title: Effects of the Antiepileptic Medication Valproic Acid Sodium Salt (VPA) on the Histological Bone Structure
Advisor: Dr. Drew Crain
Epilepsy and seizures affect approximately 2.2 million people in the United States with approximately 200,000 new cases diagnosed each year. Due to neither an effective prophylaxis nor an available cure, antiepileptic medications serve as the treatment of choice in reducing and suppressing seizure activity. Some of these antiepileptic medications exhibit adverse side effects. Although it is commonly acknowledged that enzyme-inducing antiepileptic drugs (e.g., carbamazepine, phenytoin, and phenobarbital) cause osteoporosis, valproic acid sodium salt is a well-known cytochrome P450 enzyme and estrogen inhibitor that has shown mixed results on affecting bone density. This study used an amphibian model (Xenopus laevis) to investigate the effects on bone density after thirty-day exposure to the anti-epileptic drug valproic acid sodium salt (VPA). Histological analysis of the femurs (n=4 exposed, n=4 controls) showed that VPA did not influence the number of osteoblasts or osteocytes within the diaphysis of the femur (p = 0.4384 and p = 0.4799, respectively). Similarly, the number of chondrocytes within epiphyses of femur was not affected by the drug (p = 0. 1335). In conclusion, VPA exposure led to no significant affect on bone density in X. laevis. Future studies should examine the effect of chronic use of VPA and VPA combined administration with supplements containing both calcium and vitamin D, an osteopenia preventative method recommended by physicians.
By Kristi L. Nelson, Knoxville News Sentinel
Published Dec. 6, 2013
When Mallory Kirkland looked through the microscope at a frog femur, she felt like she might be looking at her future — in more ways than one.
Kirkland, 21, a senior at Maryville College, plans a career in medicine, probably orthopedics. She also has epilepsy.
And she just spent the last year working on a research project that combined both interests: a look at whether a certain type of drug used to treat epilepsy affected bone mineral density over time.
“Going into the study, I was thinking, ‘Oh, my goodness, I’m going to be taking this drug for who knows how long — am I also going to have osteoporosis?’” Kirkland said.
Kirkland’s study used a frog model to study the effects of valproic sodium salt on the cells in the leg bone. She used African pond frogs as models; because they absorb the drug directly through their skin, it was easy to control the amount they received by putting it in the water in their tanks, she said. There was also a control group, which got plain water without the drug.
Studies have shown some other drugs used to control epilepsy do decrease bone density, as well as estrogen. It especially could affect women who have serious or frequent seizures and must take the drug long-term, into the later years, Kirkland said.
For 30 days, Kirkland gave the frogs 60 milligrams of valproic sodium salt each.
“She was mimicking exactly what humans are exposed to, just in a frog,” said her adviser, biology professor Drew Crain.
At the end of that period, she euthanized the frogs, microdissected them, and prepared them for study. Then she went home to Alabama for three months over the summer.
“It’s all I was thinking about — hope I closed all those correctly!” she said, laughing.
Once back at Maryville College for the fall semester, Kirkland studied the frog femur bones, paying close attention to the number of cells in certain cartilage and at the edge of the bone marrow.
Counting them, she found the drug “did NOT affect any of the bone cells,” she said. “That was actually a good thing for me, personally.”
Kirkland was diagnosed with epilepsy her senior year of high school, after she passed out in a department store and struck her head on a 2-inch glass shelf — “split it right open,” she said.
She speculates that her epilepsy might have been dormant until that “trigger”; she’s had four seizures since. She takes medication, though not the same medication she studied.
Kirkland hopes to further study VPA and bone density with a larger experiment.
“The one limitation on this is sample size,” Crain said — she used only eight frogs. “That’s abysmally small, we know.”
But he said Kirkland’s work could be submitted to a science journal that specializes in undergrad projects.
“This was a study that not only affected me, it interested me,” Kirkland said. “I was really passionate about it.”