| BackgroundEpilepsy is one of the most common neurological diseases,which is mainly controlled by antiepileptic drugs(AEDs)including traditional AEDs and newly AEDs.It is essential for most patients with epilepsy to take AEDs for a long term.A large number of studies have shown that long-term application of AEDs has negative effects on bone health.It is often manifested by changes in the bone metabolism biochemical markers,decreased bone mineral density(BMD),leading to increased risk of osteoporosis,fractures and osteomalacia,which seriously affects the quality of life of patients.However,it is very difficult to raise people's awareness of adverse effects of AEDs since patients with epilepsy who take AEDs will not show clinical manifestations related to bone abnormality for years or even longer.The bone metabolism biochemical markers include calcium and phosphorus metabolism indicators(calcium,phosphorus,vitamin D3 and etc.),bone formation markers(type I procollagen amino-terminal peptide,etc.),bone resorption markers(type I collagen carboxy-terminal peptide,etc.),hormone and cytokine.Bone formation markers and bone resorption markers are collectively referred to as bone turnover markers.Bone metabolism biochemical markers can reflect the state of bone turnover in a timely manner and have been widely used in the evaluation of bone metabolism abnormalities caused by AEDs.Studies have found that traditional AEDs have more adverse effects on bone metabolism than newly AEDs,including hypocalcemia,vitamin D insufficiency or deficiency,changes in bone transformation markers,and decreased bone mineral density.However,evidence have indicated that the effects of AEDs,especially newly AEDs,on bone metabolism are still controversial.More clinical researches are needed to evaluate the impact of AEDs on bone metabolism and guide clinical diagnosis and treatment.ObjectiveTo evaluate the effects of AEDs on bone metabolism biochemical markers in patients with epilepsy,we compared serum calcium(Ca),phosphorus(P),vitamin D3(VD3),type I procollagen amino-terminal peptide(PINP)and type I collagen carboxy-terminal peptide(CTX)levels in the patients with epilepsy who had taken AEDs for at least 12 months and control subjects.To assess the effects of gender,number and type of AEDs on bone metabolism,we compared the abovementioned bone metabolism biochemical markers in different groups of male and female,AEDs monotherapy and polytherapy,enzyme inducing antiepileptic drugs(EIAEDs)and non-enzyme inducing antiepileptic drugs(NEIAEDs).We also assess the correlation between serum bone formation marker PINP,bone resorption marker CTX levels and serum concentration of Ca,P and VD3.MethodsAccording to the new clinical definition of epilepsy proposed by the International League Against Epilepsy(ILAE)in 2014,this study included 90 clinically diagnosed epilepsy patients who took AEDs orally for at least 12 months.Subjects with chronic active illness and taking medications known to affect bone metabolism were excluded.At the same time,90 newly diagnosed epilepsy patients who hadn't taken any AEDs with age,gender and case groups were selected as the control group.According to the number of oral AEDs,patients were divided into two subgroups of AEDs monotherapy and polytherapy;according to the type of AEDs,patients were divided into two subgroups of enzyme inducing antiepileptic drugs(EIAEDs)and non-enzyme inducing antiepileptic drugs(NEIAEDs).We also compared bone metabolism biochemical markers in monotherapy group of Oxcarbazepine(OXC),Carbamazepine(CBZ)and Levetiracetam(LEV).Serum samples from patients with epilepsy and controls were obtained by venous blood collection.Serum Ca and P concentrations were measured by biochemical analysis methods;serum VD3,PINP,and CTX concentrations were determined by enzyme linked immunosorbent assay(ELISA).The statistical analysis software SPSS 25.0 was used to compare the concentrations of serum markers in the experimental group and the control group in order to analyze the effects of AEDs on bone metabolism and the effects of the number and type of AEDs on bone metabolism were also explored,and we also analyze the correlation between serum bone formation marker PINP,bone resorption marker CTX levels and serum Ca,P and VD3 levels in the experimental group.ResultsBy independent t-test comparison,the expression level of serum Ca(2.35±0.07 mmol/L)in epilepsy patients in the experimental group was significantly lower than that in the control group(2.42±0.03 mmol/L,P<0.001);the expression level of serum P in epilepsy patients in the experimental group(1.35±0.07 mmol/L)L)was significantly lower than that in the control group(1.39±0.10 mmol/L,P=0.002);the expression level of serum VD3(19.46 ±6.68 ng/ml)in epilepsy patients in the experimental group was significantly lower than that in the control group(25.21±5.15 ng/ml,P<0.001);the expression levels of serum CTX(Male 1.05±0.21 ng/ml;Female 1.11±0.19 ng/ml)were significantly higher than those in controls(Male 0.81±0.34 ng/ml,P<0.001;Female 0.81±0.25 ng/ml,P<0.001).By Mann-Whitney U test comparison,the expression levels of serum PINP(median male:52.23 ng/ml;female:51.28 ng/ml)in epilepsy patients in the experimental group were significantly higher than those in the control group(median male:35.96 ng/ml,P<0.001;female:37.24 ng/ml,P<0.001).By chi-square test,the VD3 deficiency rate in epilepsy patients in the experimental group was 54.44%,which was significantly higher than that in the control group(17.78%,P<0.001).However,there were no other significant differences in the expression levels of serum Ca,P,VD3,PINP,and CTX that were related to the gender,the types of AEDs and the numbers of AEDs.Spearman correlation analysis showed that there was no correlation between serum PINP levels and serum Ca,P,VD3 levels in the epilepsy patients in the experimental group;Pearson correlation analysis showed that serum CTX levels in the experimental group epilepsy patients were negatively correlated with serum Ca levels(r=-0.222 P=0.035),no correlation with serum P and VD3 levels.Conclusions1.The expression levels of serum Ca,VD3,P in patients with epilepsy who take AEDs are significantly lower than those in patients who don't take AEDs;2.The expression levels of serum PINP and CTX in patients with epilepsy who take AEDs are significantly higher than those in patients who don't take AEDs;3.The deficiency rate of VD3 in patients with epilepsy who take AEDs is significantly higher than those in patients who don't take AEDs;4.Vitamin D deficiency or insufficiency is common in patients with epilepsy.5.Serum bone resorption marker CTX level in patients with epilepsy taking AEDs is negatively correlated with serum Ca level. |
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