Antiepileptic drugs and reduced bone mineral density

Abstract

There is a growing interest in recognizing the association between antiepileptic drugs and reduced bone mineral density. Although the literature regarding this association has been available for more than three decades, the management of this complication remains unclear. We review the relevant literature regarding antiepileptic drugs and reduction in bone mineral density with the aim of developing some guidelines for practical management of this problem. This review focuses on the mechanism of antiepileptic drug-induced bone loss, its recognition, and its management.

Introduction

The American Epilepsy Society Practice Committee was established by the board members to inform members of important practice issues and assist them in keeping abreast of the latest practice approaches and administrative/management challenges. In 2002, the authors were asked to review the data regarding effects of bone density and antiepileptic drug therapy and develop a consensus document for review and dissemination within the committee and for practicing physicians. The authors then presented these data at the 2002 AES Practice Annual Meeting. All committee members approved it unanimously. The intent of this document is to provide information that can be translated into clinical practice based on review of all the relevant literature.

The effects of antiepileptic drugs on bone mineral density have been known for more than 30 years [1], [2], [3], [4]. There is an extensive body of literature that suggests that antiepileptic drugs can produce hypocalcemia, decrease biologically active vitamin D levels, and lead to reduced bone mineral density [3], [4], [5], [6], [7], [8]. However, a recent survey found that only less than a third of neurologists were aware of such an association and routinely evaluated patients for bone and mineral disease [9]. Even more concerning was the finding that only 7–9% of neurologists polled gave prophylactic vitamin D or calcium supplementation.

Clinically obvious osteomalacia or osteoporosis is relatively uncommon, but can be documented by sophisticated radiological, laboratory, or pathological techniques [10], [11], [12], [13], [14], [15], [16] in a significant number of patients receiving antiepileptic medications. Most of the available data pertain to older and conventional antiepileptic drugs (AEDs), such as phenytoin, phenobarbital, carbamazepine, and divalproex sodium [17], [18], [19], [20], [21], [22], although data on newer agents are beginning to be published [19].