Antiepileptic drugs and bone metabolism

Abstract

Anti-epileptic medications encompass a wide range of drugs including anticonvulsants, benzodiazepines, enzyme inducers or inhibitors, with a variety effects, including induction of cytochrome P450 and other enzyme, which may lead to catabolism of vitamin D and hypocalcemia and other effects that may significantly effect the risk for low bone mass and fractures. With the current estimates of 50 million people worldwide with epilepsy together with the rapid increase in utilization of these medications for other indications, bone disease associated with the use of anti-epileptic medications is emerging as a serious health threat for millions of people. Nevertheless, it usually goes unrecognized and untreated. In this review we discuss the pathophysiologic mechanisms of bone disease associated with anti-epileptic use, including effect of anti-epileptic agents on bone turnover and fracture risk, highlighting various strategies for prevention of bone loss and associated fractures a rapidly increasing vulnerable population.

Figure 1

Development of osteoblasts and osteoclasts from bone marrow progenitors. Factors affecting the development and function of these cells, bone resorption by osteoclast and new bone formation by osteoblasts. Abbreviations: GH: growth hormone, IGF: insulin like growth factors, PTH: parathyroid hormone

Figure 2

Decrease in peak bone mass with age and increase in fracture risk with increasing age.

Figure 3

Representation of pregnane X receptor (PXR) mediated vitamin D catabolism. PXR is activated by various antiepileptic medications and other pharmaceutical agents and induces CYP 24, the enzyme which metabolises active vitamin D₃ to inactive form. Abbreviations: PXR: Pregnane X receptor, DPH: phentyoin, CBZ: carbamazepine, PB: phenobarbital, VDR: vitamin D receptor, PTH: parathyroid hormone, CYP 24: 24-hydroxylase.