Bone mass and turnover in women with epilepsy on antiepileptic drug monotherapy

Abstract

Antiepileptic drugs, particularly cytochrome P450 enzyme inducers, are associated with disorders of bone metabolism. We studied premenopausal women with epilepsy receiving antiepileptic drug monotherapy (phenytoin, carbamazepine, valproate, and lamotrigine). Subjects completed exercise and nutrition questionnaires and bone mineral density studies. Serum was analyzed for indices of bone metabolism including calcium, 25-hydroxyvitamin D, parathyroid hormone, insulin growth factor I, insulin binding protein III, and bone formation markers, bone-specific alkaline phosphatase, and osteocalcin. Urine was analyzed for cross-linked N-telopeptide of type I collagen, a bone resorption marker. Calcium concentrations were significantly less in subjects receiving carbamazepine, phenytoin, and valproate than in those receiving lamotrigine (p = 0.008). Insulin growth factor-I was significantly reduced in subjects receiving phenytoin compared with those receiving lamotrigine (p = 0.017). Subjects receiving phenytoin had significantly greater levels of bone-specific alkaline phosphatase (p = 0.007). Our results demonstrate that phenytoin is associated with changes in bone metabolism and increased bone turnover. The lower calcium concentrations in subjects taking carbamazepine or valproate compared with those taking other antiepileptic drugs suggest that these antiepileptic drugs may have long-term effects. Subjects receiving lamotrigine had no significant reductions in calcium or increases in markers of bone turnover, suggesting this agent is less likely to have long-term adverse effects on bone.

An International Multicenter Randomized Double‐Blind Controlled Trial of Lamotrigine and Sustained‐Release Carbamazepine in the Treatment of Newly Diagnosed Epilepsy in the Elderly

“…These include the risk of drug interactions with comedications frequently taken by elderly patients Perucca, 2003a, 2003b), and adverse effects on endocrine function and bone mineralization . Because of its lack of enzyme-inducing effects, LTG may be preferable to CBZ in minimizing these concerns (Morrell, 2003;Pack et al, 2005).…”

Bone density and bone turnover markers in patients with epilepsy on chronic antiepileptic drug therapy

“…In their study, an increase in markers of bone turnover was seen after 2 years, but vitamin D metabolism was normal in all pubertal stage groups. In contrast, 2 other studies have failed to find an association between carbamazepine and altered bone turnover (15,26 One of the limitations of the present study is the cross-sectional nature, where BMD was measure only once, turning it difficult to know if the low bone density observed in the patients group is specifically related to AEDs use. However, by the fact that other secondary causes were excluded and the patients presented lower BMD than the control matched group, we do believe that the use of AEDs may play a role on this issue.…”

“…Other drugs that are not enzyme inducers, such as sodium valproate, may exert indirect effects on bone metabolism by altering renal function (12). In addition, it has been reported that AEDs lead to an increase in bone turnover, as demonstrated by elevated levels of bone turnover markers (13)(14)(15)(16).…”

Abdominal Pain Caused by Bilateral Acetabular Fractures Secondary to an Epileptic Seizure Case Report and Review of the Literature

“…In 40% of epileptic patients the fracture is associated with osteopenia, which is either due to physical impairment, postmenopausal state, or related to anti-epileptic drugs (AED) [4,5]. by altering osteoblastic function, may affect intestinal calcium absorption and can induce anticonvulsant osteopathy [15][16][17]. Our patient did not use any AEDs.…”