Seizure: European Journal of Epilepsy
Volume 19, Issue 6 , Pages 324-325, July 2010

Fractures in epilepsy children

Outpatient Clinic of Child Neurology and Epileptology, 25-565 Kielce, Kościuszki Str. No. 52/012, Poland

Received 19 November 2009; received in revised form 11 April 2010; accepted 23 April 2010. published online 21 May 2010.

Article Outline

Abstract 

Purpose

To describe a greater risk of fractures (about 2–6 times more often) in epilepsy children than in children without epilepsy.

Methods

This article describe 126 epilepsy children in age 7–16 who were treated with Antiepileptic Drugs (AEDs) in mono and add-on therapy during 5 years. In the control group were 132 children in age 7–16 without epilepsy and not treated with AEDs, observed in Outpatient Clinic due to headache for 5 years. In both groups we measured bone mineral density (BMD), the calcium and phosphate levels in blood and urine and frequency of fractures. We analyzed both groups statistically (Mann–Whitney test).

Result

The frequency of fractures is 2–3 times greater in children with epilepsy then in the control group. Osteoporosis and osteopenia is more often present in children who have taken AEDs.

Differences in calcium and phosphate levels in blood and urine between study and control group are statistically significant (p<0.001).

Conclusion

Fractures are an important adverse effect in children who are taking AEDs.

Keywords: Fractures, Bone mineral density, Osteopenia, Epilepsy, Antiepileptic drugs

 

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1. Introduction 

Fractures in epilepsy are frequent in children and adults as was described in literature.5, 12, 13, 15 Risk of fractures in children after a few years of taking AEDs is two to six times greater than in the general population.5, 12 Low BMD has been very often associated with AEDs therapy.11

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2. Methods 

We have been observing 126 children in age 7–16 with epilepsy (80 boys and 46 girls) during 5 years (2003–2007). This study group was treated with different antiepileptic drugs: valproid acid (VPA), carbamazepine (CBZ), lamotrigine (LTG) and topiramate (TPM) in mono and add-on therapy. Monotherapy was administered to 59 patients (47%), add-on therapy to 67 patients. The monotherapy group consist of: children on VPA: 16, children on CBZ: 7, children on LTG: 26, children on TPM: 10. The add-on therapy group consist of: children on VPA+CBZ: 19, children on VPA+LTG: 32, children on VPA+TPM: 13, children on LTG+TPM: 3. Valproid acid was an element of therapy in 80 patients (63%): 16 patients on monotherapy and 64 on add-on therapy. Children with epilepsy were classified into two groups with different types of epilepsy using the Terminology of International League Against Epilepsy System from 19897: generalized epilepsy in 99 children and localization-related epilepsy in 27 children.

The control group consisted of 132 healthy children in age 7–16 (87 boys and 45 girls).

Both in study and control group was measured bone mineral density and z-score using dual energy X-ray (DEXA) technology (DTX-200-V 1.63, Meditechnet). The measurement was taken in the areas of lumbar spine and proximal femur. We have also assessed the calcium and phosphate levels in blood and urine in both groups.

All children has been on normal or rich in calcium and phosphate diet. All patients had normal physical activity. All group were statistically analyzed using Mann–Whitney U-test.

All patients gave written informed consent and the local Ethic Committee had approved the study.

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3. Results 

The 126 patients and 132 controls had different scores of bone mineral density (0.901±0.251 and 0.983± respectively) (p<0.00156). BMD was significantly lower in study group compared to controls.

Mean in study group in blood calcium level was 9.06±0.36 (mg/dL) whilst in the control group it was 9.32±0.33 (p<0.000001). Blood phosphate level mean in study group was 3.45±0.26 (mg/dL) and in controls 4.14±0.3 (p<0.000001). The calcium and phosphate levels in blood were significantly lower in epilepsy children group. In urine mean of calcium level in study group was 130±22 (mg/24h) and in control group 147±28 (p<0.000001) which means it was significantly lower in study group. The mean of phosphate level in urine were in epilepsy children 3.41±0.78 (g/24h) and in controls 1.76±0.62 (p<0.000001). These findings demonstrates that phosphate levels in urine were significantly higher in epilepsy children who treated with AEDs during 5 years.

The means of bone mineral density (BMD, g/cm2) in epilepsy children were significantly lower then in controls (0.901±0.251 and 0.983±0.121) (p<0.00156).

In study group osteoporosis (z-score<−2.5) was observed in 9 children and osteopenia (z-score between −1 and −2.5) was found in 29 children in comparison with control group where no child suffered from osteoporosis and osteopenia was found in 8 children.

In epilepsy group 43 patients had fractures while in control group only 19 children had fractures (34% in study group comparison of 14% in control group). This means the fractures are 2.26 times more frequent in study group. The fractures in both groups were single and simple, limited to bones of lower and upper extremities. The majority of those were the green-stick fractures.

In epilepsy group 10 patients on monotherapy had fractures and from the add-on therapy group it was 33 patients. In both groups (monotherapy and add-on therapy group) of patients who had fractures, valproid acid is frequently used (35 patients on VPA in a group of 43 patients with fractures, which means 81% of patients on VPA in the group of patients with fractures). The type of therapy (especially therapy with VPA and add-on therapy) had high influence in all scores in my study. The majority of children was taking valproid acid due to generalized and secondary generalized epilepsy and this medicine had high impact on BMD, as well as calcium levels and phosphate levels in blood and urine.

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4. Discussion 

Many authors discuss about patients treated with AEDs and have analyzed an impact AEDs (especially VPA, CBZ and the add-on therapy) have on bone mineral density and fractures in children.1, 2, 3, 8, 12, 13, 15 It is very possible that lower BMD score is a result of lower calcium and phosphate levels in blood and lower calcium and higher phosphate level in urine in epilepsy children.2, 5, 9, 10, 11, 12, 13, 14 The epilepsy children with generalized and secondary generalized epilepsy very often take VPA as the first-line therapy in monotherapy and add on-therapy. Valproid acid was told to have a big influence in calcium and phosphate levels and in bony mineral density according to many authors.1, 3, 4, 6, 8, 14 After 5 years of observation of children treated with AEDs we came to conclusion that the greater number of fractures was a result of lower bone mineral density in children with epilepsy.5, 12, 13 We feel it very important to state that a diet rich with vitamin D and calcium and phosphate improves the bone function.

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5. Conclusions 

Fractures are more frequent in children with epilepsy, especially in those who are treated with VPA and are on the add-on therapy.

Children with epilepsy treated with AEDs have a significantly lower z-score, lower calcium levels in blood and urine, lower phosphate level in blood and higher phosphate level in urine in comparison with control group.

Differences are statistically significant (p<0.01).

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Conflict of interest 

The author report no conflicts of interest.

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Acknowledgements 

This work was not supported. This study was made in my Outpatients Clinic.

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References 

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PII: S1059-1311(10)00088-9

doi:10.1016/j.seizure.2010.04.013

Seizure: European Journal of Epilepsy
Volume 19, Issue 6 , Pages 324-325, July 2010

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