Effects of Chronic Administration of Zonisamide, an Antiepileptic Drug, on Bone Mineral Density and Their Prevention With Alfacalcidol in Growing Rats

Abstract

Abstract. We investigated the effects of chronic administration of zonisamide, an antiepileptic agent, on bone metabolism in growing rats. Administration of zonisamide at a dose of 80 mg / kg per day, s.c. for 5 weeks significantly decreased bone mineral density (BMD) at the tibial metaphysis and the diaphysis. The percent rate of decrease in BMD at the tibial metaphysis and the tibial diaphysis was 9.2% and 5.0%, respectively. There was no significant difference between these groups in the growth of the rats. Treatment with zonisamide at a dose of 80 mg / kg increased serum pyridinoline level, a marker of bone resorption, while it does not affect the serum intact osteocalcin level, a marker of bone formation. Combined administration of alfacalcidol, an active vitamin D 3 metabolite, at a dose of 0.1 mg / kg per day with zonisamide prevented a decrease in BMD and showed an increase of serum pyridinoline levels. These results suggest that zonisamide may cause bone loss by accelerating bone resorption rather than inhibiting bone formation. Moreover, the bone loss induced by zonisamide could be prevented by combining zonisamide with alfacalcidol.

Effects of zonisamide monotherapy on bone health in drug‐naive epileptic patients

“…A previous study including rats reported that the administration of ZNS at a dose of 80 mg/ kg for 5 weeks had a significant negative impact on bone density at the metaphysis and diaphysis of the tibia. 31 It was suggested that ZNS treatment elevated serum pyridinoline levels (bone resorption marker) while not affecting serum osteocalcin (a bone formation marker), which implies that ZNS might cause bone loss by accelerating bone resorption. However, there is a dearth of human studies regarding the association between ZNS and bone health.…”

Molecular mechanisms responsible for the impact of antiepileptic therapy on bone mineral density of epileptic patients

“…В экспериментальном исследо-вании A. Takahashi и соавт. [67] показано значительное сни-жение МПК в метафизе и диафизе большеберцовой кости и повышение уровня сывороточного пиридинолина (pyridinoline -PYD) на фоне приема ЗНС у крыс.…”

Drug and Hormone Effects on Vitamin D Metabolism

“…Yet, osteoporosis has been reported in children on chronic valproic acid therapy [349,350], and long-term use of valproate and lamotrigine has been shown to be associated with reduced bone formation [351]. Animal studies using zonisamide have shown a significant decrease in BMD [352,353]; however, this has been attributed to carbonic anhydrase inhibition [346]. Limited data exist on the effects of levetiracetam on vitamin D metabolism.…”