Comparison between the effects of older versus newer generations of antiepileptic drugs on bone metabolism in adult Iraqi patients: an observational study [version 1; peer review: awaiting peer review]

Background: Metabolic bone disorder is a significant endocrine system disorder that encompasses any disorder that alters the natural skeleton's mineralization process. Epilepsy is a prevalent central nervous system disorder that can cause biochemical abnormalities involving bone metabolism in the epileptic patients. The present study aimed to investigate the effects of chronic use of older compared to the newer generations of antiepileptic drugs on bone metabolism-related biomarkers. Methods: The study included fifty-one epileptic outpatients who attended the Consultation Clinic of Baghdad Teaching Hospital at the Medical City Complex from October/2021 to December/2021. The selected patients were on antiepileptic drugs for more than 2 years, hence were grouped according to their antiepileptic therapy into: Group-1: 24 epileptic patients on old antiepileptic drugs (Carbamazepine or Valproate). Group-2: 27 epileptic patients on new antiepileptic drugs (Levetiracetam), compared with Group-3: 28 healthy control subjects. Serum was obtained from their blood specimens to measure: calcium and inorganic phosphate by colorimetric assays, parathyroid hormone, and level of bone alkaline phosphatase activity. Results: Data analysis revealed that the median value of serum parathyroid hormone levels was significantly elevated in the epileptic patients' groups compared to the healthy control group. However, group-2 D levels bone if other liver function tests are normal. calcium levels appear to be linked to greater ALP and low vitamin D levels. Hale Maral Kir et al. (2012) study found a significant difference was not found between control groups and carbamazepine groups in terms of mean serum BAP. 15 The results of a study by Buket Tuan Yldz et al . (2021) showed that epilepsy patients ’ serum levels of BAP were lower than healthy control persons. Because these are indications of enhanced bone formation, the low levels in AED users show that anti-epileptic drugs have a direct impact on bone mineralization. 12 The frequency of patients with abnormal biochemical parameters and the laboratory results of the analyzed groups. Patients had reduced serum calcium, 25(O.H.) D, and OPG and increased ALP compared to control volunteers. 36 In ambulatory adults with epilepsy and on chronictreatment with AEDs,thereisanincreasedriskofboneloss(osteopenia/osteoporosis) and fracture, hypocalcemia (52%) and 25(OH) D deficiency/insufficiency, increased bone turnover as indicated by lower serum levels of OPG and higher levels of sRANKL and sRANKL/OPG ratio (markers of bone remodeling), and metabolic bone compromise with prolongation of the duration of treatment with AEDs due to disturbed mineral metabolism associated with compromise of bone remodeling with accelerated bone turnover. biochemical abnormalities of bone-related mineral metabolism included hypocalcemia (52%) and hypovitaminosis D (93.33%). 25(OH) D levels were positively correlated with calcium levels. 36 This studyreported that theserum bone alkaline phosphatase activity theof the studiedgroups (group-1, group-2 and control). Significant differences betweenthe epileptic patients (group-1,group-2); aswell as with thehealthy control subjects. The other common laboratory abnormalities described in relation to AED are elevated levels of ALP and hyperparathyroidism. 40 hepatic induction of cytochrome P450 enzymes by AEDs