Abstracts

Rationale: Significant effects of classic enzyme inducers such as phenytoin and carbamazepine on bone density and on laboratory markers of bone metabolism have been demonstrated already after short observation periods. It is assumed that the negative effect of the cytochrome P450 (CYP450) inducers on bone metabolism is caused by the increased metabolism of 25-hydroxycholecalciferol (25-OHD) to biologically less active metabolites. For oxcarbazepine, which like eslicarbazepine acetate (ESL) is a less potent inducer of CYP450, some studies have shown that treatment was associated with reduced levels of 25-OHD and increased bone metabolic parameters. There is evidence that ESL may exert mild to moderate effects on bone metabolism. However, the effect on bone density has not yet been systematically investigated.

Methods: In an observational study (BONAPARTE), standardized osteodensitometry was performed at the time of introduction of ESL and 1 year after continued therapy. In addition, bone metabolism parameters (25-OHD, parathyroid hormone, osteocalcin, bone-specific alkaline phosphatase) after 12 months under ESL therapy were compared with the baseline value.

Results: 23 patients (8 female) were included, age 40.3 ± 12.8. The mean daily dose of ESL at the 12-month follow-up was 1130 ± 425 mg. 3/23 patients had comedication with an enzyme inducer at baseline. 6/23 patients had a preexisting pathological finding in osteodensitometry at baseline.

At the group level, there were no significant effects under the treatment with ESL on parameters in standardized osteodensitometry. Mean values of bone density in g/cm² at baseline were 1.2 (±0.17) at lumbar spine and 0.98 (±0.14) at proximal femur. After 12 months of ESL treatment 1.15 (±0.16) at lumbar spine; and 0.97 (±0.12) at proximal femur. In 2/23 patients, there was a clinically significant decrease in bone density measured on the proximal femur (one patient on monotherapy with ESL, one patient with one consecutively changed concomitant AED (levetiracetam, brivaracetam, perampanel)). In another patient treated concomitantly with 100 mg zonisamide, the bone density decreased significantly in the area of the lumbar spine. One 32-year-old male patient developed a clinically significant change in bone density on the femoral neck with de novo osteopenia under polytherapy with ESL 1600 mg/d; brivaracetam 200 mg/d and perampanel 6mg/ d). In this patient, the 25-OHD level fell clinically significantly from 32.6 to 8.2 ng / ml, and parathyroid hormone rose from 35 to 50 pg/ml. At the group level, however, there were no significant metabolic alterations.

Conclusions: Neither osteodensitometry nor bone metabolism parameters showed significant group effects after one year of treatment with eslicarbazepine acetate. Individual fluctuations were observed, however, which may warrant monitoring particularly in patients under polytherapy.

Funding: Please list any funding that was received in support of this abstract.: The observational study (BONAPARTE) was funded by BIAL.