The effect of levetiracetam and oxcarbazepine monotherapy on thyroid hormones and bone metabolism in children with epilepsy: A prospective study

Shi, Kaili; Guo, Junxiu; Zhao, Huimin; Han, Hong; Yang, Chuanzi; Wu, Yunhong; Du, Lijun

doi:10.1016/j.yebeh.2020.107555

Cited by 19 publications

(16 citation statements)

References 27 publications

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“…There are a variety of mechanisms by which ASMs may alter bone metabolism, including catabolism of vitamin D, increasing parathyroid hormone levels, 1 exhibiting adverse effects on sex steroids, 2 having a direct link and influence on bone cells, 3 and increasing levels of homocysteine, 4 which has been shown to reduce bone strength through a cascade of biological events 35 . It is generally believed that OXC is a weak inducer of liver enzymes and alters thyroid function, 21 leading to secondary hyperparathyroidism via altered metabolism of vitamin D, calcium, and phosphorous. If LEV interacts with bone metabolism, the mechanisms of action are not well known.…”

Section: Discussionmentioning

confidence: 99%

“…19,20 Currently, data regarding the effect of LEV and OXC on bone fragility among prepubertal and pubertal children with epilepsy are limited and contradictory. Several studies with small sample sizes in children with epilepsy treated with LEV reported unaltered biomarkers of bone metabolism and bone mass, [21][22][23] whereas a rat model treated with low-dose LEV reported reduced bone strength in the femoral neck, despite no changes in bone mass. 24 Studies have reported that OXC treatment may reduce levels of relevant bone metabolic biomarkers (e.g., osteocalcin, vitamin D) 18,22,25 and bone mass in children with epilepsy.…”

Section: Introductionmentioning

confidence: 99%

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Effect of levetiracetam and oxcarbazepine on 4‐year fragility fracture risk among prepubertal and pubertal children with epilepsy

et al. 2021

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Objective The objective of this study was to determine whether two commonly prescribed antiseizure medications (ASMs), levetiracetam (LEV) and oxcarbazepine (OXC), were associated with an increased risk of fragility fracture in children with epilepsy when initiating therapy during a crucial period of bone development, namely, pre‐ and midpuberty. Methods Claims data from January 1, 2009 to December 31, 2018 were extracted from the Optum Clinformatics Data Mart. Children aged 4–13 years at baseline with at least 5 years of continuous health plan enrollment were included to allow for a 1‐year baseline (e.g., pre‐ASM exposure) and 4 years of follow‐up. Children with epilepsy who were ASM naïve were grouped based on whether ASM treatment initiation included LEV or OXC. The comparison group included children without epilepsy and without ASM exposure. Crude incidence rate (IR; n per 1000 person‐years) and IR ratio (IRR; with 95% confidence interval [CI]) were estimated for nontrauma fracture (NTFx), a claims‐based proxy for fragility fracture, for up to 4 years of follow‐up. Cox proportional hazards regression estimated the hazard ratio (HR; with 95% CI) after adjusting for demographic variables, motor impairment, and baseline fracture. Results The crude IR (95% CI) of NTFx was 21.5 (21.2–21.8) for non‐ASM‐users without epilepsy (n = 271 346), 19.8 (12.3–27.2) for LEV (n = 358), and 34.4 (21.1–47.7) for OXC (n = 203). Compared to non‐ASM‐users, the crude IRR of NTFx was similar for LEV (IRR = .92, 95% CI = .63–1.34) and elevated for OXC (IRR = 1.60, 95% CI = 1.09–2.35); the crude IRR of NTFx was elevated for OXC compared to LEV (IRR = 1.74, 95% CI = 1.02–2.99). The findings were consistent after adjusting for covariates, except when comparing OXC to LEV (HR = 1.71, 95% CI = .99–2.93), which was marginally statistically insignificant (p = .053). Significance Initiating OXC, but not LEV, therapy among 4–13‐year‐olds with epilepsy is associated with an elevated risk of fragility fracture. Studies are needed to determine whether these children could benefit from adjunct bone fragility therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of levetiracetam and oxcarbazepine on 4‐year fragility fracture risk among prepubertal and pubertal children with epilepsy

et al. 2021

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“…Although several studies reported that oxcarbazepine could result in reduction in free T4 with little impact on TSH, all the previous studies were conducted in epilepsy patients with small sample sizes. [11][12][13][14][15][16]29,30 Some of these studies had cross-sectional study design, 15 with incomplete laboratory tests, 29 with no comparison to oxcarbazepine nonusers, 11,29,30 or without information on whether thyroxines concentrations reached cut-off values. 30 The oxcarbazepine label discloses decrease in T4 with unclear clinical significance and hypothyroidism as a frequency not reported side effect.…”

Section: Discussionmentioning

confidence: 99%

“…[11][12][13][14][15][16]29,30 Some of these studies had cross-sectional study design, 15 with incomplete laboratory tests, 29 with no comparison to oxcarbazepine nonusers, 11,29,30 or without information on whether thyroxines concentrations reached cut-off values. 30 The oxcarbazepine label discloses decrease in T4 with unclear clinical significance and hypothyroidism as a frequency not reported side effect. 31 Our finding that oxcarbazepine use was associated with higher risk of developing hypothyroxinaemia was generally consistent with previous studies where oxcarbazepine reduced T4/free T4 values but did not significantly affect TSH level in epilepsy patients.…”

Section: Discussionmentioning

confidence: 99%

Oxcarbazepine was associated with risks of newly developed hypothyroxinaemia and impaired central set point of thyroid homeostasis in schizophrenia patients

Zhai

Chen

Guo

et al. 2021

Brit J Clinical Pharma

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Aims Hypothyroxinaemia might be easily ignored, because attention is typically paid to individuals with elevated thyroid stimulating hormone (TSH). In this study, we aimed to evaluate the association of oxcarbazepine use as adjuvant for treatment of schizophrenia with hypothyroxinaemia and central set point of thyroid homeostasis. Methods This retrospective cohort study was conducted in the Second Affiliated Hospital of Xinxiang Medical University. Inpatients with a diagnosis of schizophrenia admitted between January 2016 and October 2019 with normal thyroid function at admission were included. Oxcarbazepine use was the exposure measure. Newly developed hypothyroxinaemia was the primary outcome measure and parameters of thyroid homeostasis central set point as measured by TSH index and thyroid feedback quantile‐based index (TFQI) were the secondary outcome measures. Results In total, 1207 eligible patients were included. The occurrence of hypothyroxinaemia in patients who received oxcarbazepine was higher (35/107, 32.7%) than in those patients who did not (152/1099, 13.8%), with adjusted relative risk of 2.24 and 95% confidence interval of 1.57 and 3.17. Oxcarbazepine use was associated with greater reduction in TSH index (adjusted β −0.33 and 95% confidence interval −0.48, −0.19) and TFQI (adjusted β −0.24 and 95% confidence interval −0.31, −0.16). Conclusion Oxcarbazepine use was independently associated with increased risk of developing hypothyroxinaemia, and greater reduction in TSH index and TFQI, suggesting that impaired central set point of thyroid homeostasis might be involved in the mechanism of oxcarbazepine‐induced hypothyroxinaemia.

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“…However, data in children are mixed and the effect may be small if present (51,52). Also of concern are some anti-epileptic medications, although the practical consequence of more commonly used ones in school children (e.g., levetiracetam) is likely minimal (53,54). Immunosuppressive medications used in the treatment of autoimmune disorders may affect bone health and monitoring may be needed for these children.…”

Section: Other Circumstancesmentioning

confidence: 99%

Bone Health in School Age Children: Effects of Nutritional Intake on Outcomes

Abrams

2021

Front. Nutr.

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The maximum rate of bone mass accumulation is during early adolescence. As such, a focus on optimizing mineral nutrition in school age children, defined here as approximately 5 to 15 years of age, is crucial to minimize the risk of bone loss that occurs later in life leading to osteoporosis and fractures. Optimizing bone mass in this age group requires attention to an overall healthy diet including adequate calcium, phosphorus, magnesium, and vitamin D. Special concerns may exist related to children who follow a restricted diet such as a vegan diet, those with intolerance or allergies to dairy, and those with chronic health conditions including young adolescents with eating disorders. Public policy messages should focus on positive aspects of bone health nutrition in this age group and avoid overly specific statements about the exact amounts of foods needed for healthy bones. In this regard, dietary recommendations for minerals vary between North America and Europe and these are higher than the values that may be necessary in other parts of the world. The management of many children with chronic illnesses includes the use of medications that may affect their bone mineral metabolism. Routine lab testing for bone mineral metabolism including the serum 25-hydroxyvitamin D level is not indicated, but is valuable for at-risk children, especially those with chronic illnesses.

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The effect of levetiracetam and oxcarbazepine monotherapy on thyroid hormones and bone metabolism in children with epilepsy: A prospective study

Cited by 19 publications

References 27 publications

Effect of levetiracetam and oxcarbazepine on 4‐year fragility fracture risk among prepubertal and pubertal children with epilepsy

Effect of levetiracetam and oxcarbazepine on 4‐year fragility fracture risk among prepubertal and pubertal children with epilepsy

Oxcarbazepine was associated with risks of newly developed hypothyroxinaemia and impaired central set point of thyroid homeostasis in schizophrenia patients

Bone Health in School Age Children: Effects of Nutritional Intake on Outcomes

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