Elsevier

Epilepsy & Behavior

Volume 5, Supplement 2, February 2004, Pages 24-29
Epilepsy & Behavior

Epilepsy and bone health in adults

https://doi.org/10.1016/j.yebeh.2003.11.029Get rights and content

Abstract

Adults taking antiepileptic drugs (AEDs) have an augmented risk for osteopenia and osteoporosis because of abnormalities of bone metabolism associated with AEDs. The increased fracture rates that have been described among patients with epilepsy may be related both to seizures and to AEDs. The hepatic enzyme–inducing AEDs phenytoin, phenobarbital, and primidone have the clearest association with decreased bone mineral density (BMD). Carbamazepine, also an enzyme-inducing drug, and valproate, an enzyme inhibitor, may also adversely affect bone, but further study is needed. Little information is available about specific effects of newer AEDs on bone. Physicians are insufficiently aware of the association between AEDs and bone disease; a survey found that fewer than one-third of neurologists routinely evaluated AED-treated patients for bone disease, and fewer than 10% prescribed prophylactic calcium and vitamin D. Physicians should counsel patients taking AEDs about good bone health practices, and evaluation of bone health by measuring BMD is warranted after 5 years of AED treatment or before treatment in postmenopausal women.

Introduction

Persons with epilepsy taking some antiepileptic drugs (AEDs) are at risk for bone disease. In adults, peak bone mineral density (BMD) is attained between the ages of 20 and 30 years. After age 30, there is a gradual decline in BMD. In women this is most pronounced in the years following the onset of menopause. AEDs may superimpose an additional effect on bone health; therefore, adults taking AEDs are at even greater risk for bone diseases such as osteopenia/osteoporosis, and for fracture. Identifying those AEDs that are more likely to adversely affect bone is important when choosing an AED for an adult, especially for adults with other risk factors for bone disease including Caucasian or Asian race, small frame, family history of osteoporosis and fracture, smoking history, and alcohol history. Identifying AED-treated persons with bone disease is also important, as other AEDs may have a more beneficial effect on bone, and numerous treatment options for bone disease exist. This review discusses the effects of AEDs on bone in adults, the specific AEDs associated with bone disease, treatment options, and recommendations for good bone health practices and screening for bone disease in AED-treated persons.

Section snippets

Biochemical abnormalities

Bone loss and consequent fracture appear to be a manifestation of biochemical abnormalities of bone metabolism associated with specific AEDs. These abnormalities include hypocalcemia, hypophosphatemia, reduced serum levels of biologically active vitamin D metabolites, and hyperparathyroidism. In addition, bone turnover is accelerated, as measured by markers of bone formation and bone resorption.

Calcium homeostasis and an appropriate concentration of phosphate are essential to maintain normal

Bone density abnormalities

Osteomalacia literally means softening of bone and results from reduction in bone matrix mineralization [21]. Bone biopsies of patients with AED-induced osteomalacia are histologically characterized by an increase in osteoid or unmineralized bone and reveal a mineralization defect that causes prolonged mineralization. Serum calcium, phosphate, and active vitamin D levels are abnormally low. Early reports described osteomalacia in patients treated with AEDs [1], [22]. However, these reports

Fracture

The most important clinical sequelae of bone disease are fractures. Fractures are associated with multiple morbidities, including hospitalization and loss of independence, and death. The most common fractures involve the spine and hip. Identifying patients with epilepsy who are at risk for fracture is important; particularly vulnerable are those patients who have inadequate seizure control and may sustain a fracture during a seizure.

Increased fracture rates have been described in patients with

AEDs associated with bone disease

The majority of published reports describing an effect of AEDs on bone include patients receiving phenytoin, phenobarbital, or both drugs. Fewer studies have evaluated the effect of other AEDs including carbamazepine, gabapentin, lamotrigine, oxcarbazepine, tiagabine, topiramate, valproate, and zonisamide. In addition, in many studies subjects are treated with polytherapy, which has been shown to be associated with a higher risk of bone metabolism abnormalities compared with monotherapy [3], [5]

Treatment

Although multiple therapies for bone disease are available, few studies have evaluated the effectiveness of various treatments in bone disease associated with AEDs. Calcium and vitamin D supplementation, bisphosphonates, hormone replacement therapy, selective estrogen modulators, and calcitonin are all approved treatments for bone loss. Although not approved by the U.S. Food and Drug Administration, vitamin K supplementation is being studied as a potential therapy for bone loss. Future studies

Physician awareness of AED-associated bone disease

Although the association between AEDs and bone disease was first described in the late 1960s, few physicians are aware of this long-term side effect of AEDs. A study by Valmadrid et al. [50] highlights this lack of awareness. U.S. board-certified or board-eligible pediatric and adult neurologists were surveyed about their practice patterns regarding methods of screening for bone disorders and recommendations for treatment and prophylaxis. One-third of the neurologists surveyed routinely

Recommendations

Physicians treating adults with AEDs should discuss good bone health practices. Good bone health practices include adequate sunlight exposure, adequate intake of calcium and vitamin D, regular weight-bearing exercise, and avoidance of other risk factors associated with bone disease such as alcohol use and smoking. Recommended levels of calcium intake, by age and sex, are given in Table 1.

No definitive screening or treatment guidelines are available to identify and treat persons receiving AEDs

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