Establishment Of Reference Intervals For Bone Makers In Chinese Children And To Investigate The Effects Of Epilepsy And Antiepileptic Drugs On Bone Metabolism In Pediatric Patients

Objective:To establish the reference intervals of bone metabolism markers in Chinese children; To explore effects of epilepsy itself on bone metabolism in children; and to study the effects of long-term antiepileptic drugs (AEDs) monotherapy on bone metabolism of pediatric epilepsy-BECT patients, and to provide the consultations for pediatric patients with epilepsy.Methods:A large sample multi-center cross-sectional study was performed. Detailed clinical documents were collected, and fasting blood samples were drawn from pediatric patients diagnosed with epilepsy-BECT. Automatic electrochemiluminescence immunoassay analyzer was applied for the tests of associated bone metabolism markers.Results:According to the inclusion and exclusion criteria, a total of 980 children from 20 centers aged 5 to 14 years old were enrolled, of which 284 cases were health control and 696 cases with BECT. One hundred and nineteen patients were diagnosed with BECT but without treatment,577 cases BECT patients with long-term AEDs monotherapy, which including 212 cases with oxcarbazepine (OXC),139 cases with Valproate (VPA),142 cases with levetiracetam (LEV), and 84 cases with Lamotrigine (LTG).1. Bone formation markers of P1NP and OC, as well as bone resorption markers of β-CTx have age and sex specific significant differences. The curve was drawed with age and sex. The references of bone metabolism markers were divided into three age groups, respectively in male and female.2. Compared with health control group, the patients in epilepsy-BECT group without treatment got significantly decreased (P<0.05) both bone formation and resorption markers as well as serum magnesium and PTH levels. However, Serum calcium, phosphorus, and 25-(OH)VD levels have no significant differences between the two groups.3. Compared with health control group, bone formation markers were decreased in monotherapy group with OXC, VPA, LEV, and LTG respectively (P<0.05), but had no significant differences compared with no-treatment BECT group (P>0.05), except that LTG group got increased OC and β-CTx compared with no-treatment BECT group (P< 0.05). Patients in AEDs monotherapy group had significantly decreased serum calcium concentrations compared with health control group. Serum phosphorus in VPA and LTG treatment group were lower than that in control groups (P<0.05). Patients in AEDs monotherapy group had significantly decreased serum magnesium concentrations, worse in VPA group.25-(OH)VD levels in groups had no significant differences (P> 0.05), PTH levels were significantly decreased in OXC, VPA, and LEV groups compared with health control group, but had an increased tendency in LTG group.Conclusion:1. We obtained the distribution curve of bone metabolism makers for children from 5-14 years old, and established the age and sex specific reference intervals for bone metabolism markers.2. After excluding the confounders of sun exposure, exercise, and AEDs on bone health, this study first proved that epilepsy itself could decrease the levels of serum bone metabolism markers, and damage the bone health.3. Compared with the no-treatment BECT patients, LTG could compensate for the side effects of epilepsy on bone metabolism; VPA could aggravate the bone effects; OXC and LEV had no obvious side effects on bone metabolism. Compared with the health control, the four AEDs in this study could not compensate for the side effects of epilepsy itself on bone health.