Bone Mineral Density and Periodontal Status in Patients on Antiepileptic Drug

Epilepsy is one of the most commonly encountered neurological conditions. Approximately one-third of the patients affected by this disease need to have life-long treatment with antiepileptic drugs(AEDs) . Various studies have shown that AEDs are major risk factors for bone diseases not only in institutionalized individuals and those having low Vitamin-D consumption, reduced sunlight exposure and diminished physical activity but also in non-institutionalized patients, well-nourished ambulatory adults, postmenopausal women, older men and children with this disease.The earliest reports regarding the negative effect of antiepileptic drugs on bone metabolism date back to the late 1960s. Various studies have been performed to explore the relationship between AEDs and bone metabolism but findings remain inconclusive.

AEDs are given as either monotherapy or polytherapy. In monotherapy, the antiepileptic drugs which are most commonly associated with altered bone metabolism include carbamazepine, phenytoin, primidone and phenobarbitone. New generation AEDs such as lamotrigine(LTG), topiramate, levetiracetam(LEV) are approved to be used as both antiepileptic monotherapy as well as adjuvants in combination with other AEDs. Some studies showed a negative influence of these new AEDs on bone health while other studies reported contradictory findings.

Biochemical indices are used for the measurement of blood concentration of calcium ,phosphorus, vitamin D, parathyroid hormone,bone remodelling markers like receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin(OPG). All these markers identify the patients with bone disease in an indirect way. Bone mineral density (BMD) tests have utility in detecting osteoporosis, assessing risk for bone fracture and also monitoring the response to osteoporosis therapy. Values of BMD test depend upon bone mineral content(BMC) and bone size. Dual-energy x-ray absorptiometry (DEXA) is a painless, non-invasive and easy to use technique for detection of bone mineral density (BMD) with the added benefit of low radiation exposure. It was earlier demonstrated that AEDs possess the property of enzyme induction activity through hepatic cytochrome P450 enzyme system, and this was held causative for metabolic bone diseases by increasing vitamin D metabolism, secondary type hypocalcemia and hyperparathyroidism. However, various studies have reported that both non-enzyme inducing and enzyme inducing AEDs have the potential to result in metabolic bone disease.

R.A. Seymour et al. (1985) conducted a study in which they investigated the periodontal health of adult patients with epilepsy matched in two groups and treated with either sodium valproate or phenytoin drug therapy. They reported that significantly less bone loss was observed in the phenytoin group than those on sodium valproate or the control patients. The limitation of this study was a small sample size and selection of anterior teeth only for recording periodontal parameters and alveolar bone loss.

The present study has been designed with the aim to compare bone mineral density, periodontal parameters and marginal alveolar bone levels in individuals who are on antiepileptic drugs - either sodium valproate or levetiracetam as monotherapy or on a combination regime of both the drugs(sodium valproate and levetiracetam) for at least 1 year with systemically healthy individuals. The present cross-sectional study will be conducted in the Department of periodontology, Post Graduate Institute of Dental Sciences, Rohtak in collaboration with Department of neurology, Post Graduate Institute of Medical Sciences, Rohtak.

STUDY PERIOD- January 2020 to April 2021 SAMPLE SIZE- A sample size of total 140 participants was calculated by using basic formula of sample size calculation with an moderate effect size 0.3,alpha =0.05 and power=0.80.The cross-sectional study will include 140 individuals, who will be comprised into 4 groups and the individuals in each group will be recruited as Test group 1 - individuals on antiepileptic drug sodium valproate for at least 1 year at the time of participation of the study.Test group 2- individuals on antiepileptic drug levetiracetam monotherapy for at least 1 year at the time of participation of the study.Test group 3 - individuals on antiepileptic drug sodium valproate + levetiracetam combination therapy for at least 1 year at the time of participation of the study.Control group- systemically healthy individuals.Dose of AEDs would be adjusted by treating neurologist as per the clinical response to achieve adequate seizure control.Patients in test group will be recruited from the Outpatient Department of Neurology, Post Graduate Institute of Medical Sciences, Rohtak.Patients in control group will be recruited from Department of Oral Medicine and Radiology, Post Graduate Institute of Dental Sciences, Rohtak.TEST GROUP AND CONTROL GROUP - Periodontal parameters:- 1.PLAQUE INDEX(PI) 2.GINGIVAL INDEX (GI) 3. BLEEDING ON PROBING (BOP) 4.PROBING POCKET DEPTH (PPD): 5. CLINICAL ATTACHMENT LEVEL (CAL) 6. BODY MASS INDEX (BMI) 7.CDC-AAP CASE DEFINIATIONS FOR SURVEILLANCE OF PERIODONTITIS46

1. No periodontitis- No evidence of mild, moderate, or severe periodontitis
2. Mild periodontitis- ≥2 interproximal sites with AL ≥3 mm, and ≥ 2 interproximal sites with PD ≥4 mm (not on same tooth) or one site with PD ≥5 mm
3. Moderate periodontitis- ≥2 interproximal sites with AL ≥4 mm (not on same tooth), or ≥2 interproximal sites with PD ≥5 mm (not on same tooth)
4. Severe periodontitis- ≥2 interproximal sites with AL ≥6 mm (not on same tooth) and ≥1 interproximal site with PD ≥5 mm (Third molars will be excluded; total periodontitis is defined as the sum of mild, moderate, and severe disease Radiographic parameters:-1.DUAL ENERGY X-RAY ABSORPTIOMETRY (DEXA) 2.RADIO-VISIOGRAPHY (RVG)