Aed Effects on Bone Density
Authors: Penovich Patricia E. 
Published: December 2022

Antiepileptic Drug–induced Bone Loss in Young Male Patients with Seizures

Andress DL, Ozuna J, Tirschwell D, Grande L, Johnson M, Jacobson AF, Spain W.

Arch Neurol 2002;59:781–786

Background

Long-term antiepileptic drug (AED) therapy is a known risk factor for bone loss and fractures. Vitamin D deficiency is frequently cited as a cause for bone loss in patients who have seizures.

Objective

To determine whether men who have seizures, but who are otherwise healthy, have substantial bone loss in the hip while taking AEDs. PATIENTS AND METHODS: We prospectively examined femoral neck bone mineral density (BMD) by dual-energy x-ray absorptiometry in 81 consecutive men, aged between 25 and 54 years (mean age, 45 years), who were attending an outpatient seizure clinic. Low BMD values were analyzed for known risk factors for bone loss. Dual-energy x-ray absorptiometry scans were repeated in 54 patients, 12 to 29 months later (mean, 19 months), to assess the rate of change in BMD over time.

Results

Multivariate linear regression analysis revealed that age ( P < 0.001) and time receiving AEDs ( P < 0.003) were the two important risk factors associated with low femoral neck BMD. Neither vitamin D deficiency, hypogonadism, cigarette smoking, nor excess alcohol intake was associated with low BMD after correcting for age and time taking AEDs. Longitudinal analysis of femoral neck BMD revealed that only those in the youngest age group (25–44 years) showed significant declines in femoral neck BMD (1.8% annualized loss; 95% confidence interval, −3.1 to −0.9; P < 0.003) while receiving AED therapy. There was no evidence that a specific type of AED was more causally related to bone loss in this group, although most patients were taking phenytoin sodium (PHT) or carbamazepine (CBZ) during the longitudinal assessment.

Conclusions

Long-term AED therapy in young male patients who have seizures causes significant bone loss at the hip in the absence of vitamin D deficiency. Dual-energy x-ray absorptiometry scanning of the hip is useful in identifying patients who are particularly susceptible to rapid bone loss while taking AEDs. Evaluation of Bone Mineral Metabolism in Children Receiving Carbamazepine and Valproic Acid Erbayat Altay E, Serdaroglu A, Tumer L, Gucuyener K, Hasanoglu A. J Pediatr Endocrinol Metab 2000;13:933–939 Dual energy x-ray absorptiometry (DXA) was used to assess lumbar spine (L2–4) and femoral neck bone mineral density (BMD) in 36 children taking either carbamazepine (CBZ) or valproic acid (VPA) for longer than 1 year, for generalized idiopathic epilepsy. Patients were matched with controls. Biochemical parameters of bone mineral metabolism were also measured. BMD values at both the femur neck and lumbar spine in both the CBZ and VPA groups were not significantly different from that of the control group. Serum levels of calcium were subnormal, and alkaline phosphatase levels were high in the CBZ group. Urinary calcium levels were significantly lower in both groups than in the control group ( P < 0.05) and also significantly lower in the VPA group than in the CBZ group ( P < 0.05). There were no other significant biochemical changes in either group. In conclusion, the results suggest that VPA and CBZ monotherapies have minimal effects on bone mineral metabolism, but routine monitoring of risk and consideration of prophylactic vitamin D supplementation is important. Effect of Antiepileptic Drugs on Bone Density in Ambulatory Patients Farhat G, Yamout B, Mikati MA, Demirjian S, Sawaya R, El-Hajj Fuleihan G. Neurology 2002;58:1348–1353

Background

Long-term AED use causes multiple abnormalities in calcium and bone metabolism that have been most extensively described in institutionalized patients. The objective is to determine the effect of AED on vitamin D levels and bone density in ambulatory patients and to compare the effects of enzyme-inducing and -noninducing AED and of single versus multiple therapy on bone density.

Methods

A cross-sectional evaluation was conducted of 71 patients (42 adults and 29 children/adolescents) receiving AED therapy for at least 6 months who presented to neurologists at a tertiary referral center. Bone mineral density (BMD) as well as serum 25 hydroxyvitamin D (25-OHD) levels were measured. A detailed questionnaire assessing calcium intake as well as previous and current intake of AEDs was administered to all patients.

Results

More than 50% of adults and children/adolescents had low 25-OHD levels, but this finding did not correlate with BMD. AED therapy decreased BMD in adults. Generalized seizures, duration of epilepsy, and polypharmacy were significant determinants of BMD, more so at skeletal sites enriched in cortical bone. Subjects taking enzyme-inducing drugs such as PHT, phenobarbital (PB), CBZ, and primidone (PRM) tended to have lower BMD than those taking noninducers such as VPA, lamotrigine (LTG), clonazepam (CZP), gabapentin (GBP), topamirate (TPM), and ethosuximide (ESM).

Conclusions

Epilepsy and its therapy, including the newer drugs, are risk factors for low bone density, irrespective of vitamin D levels. Skeletal monitoring with the institution of appropriate therapy is indicated in patients receiving prolonged AED therapy.