Valproate and risk of fracture in Rett syndrome

• Published in: Archives of disease in childhood 2010-06, Vol.95 (6), p.444-448
• Main Authors: Leonard, H, Downs, J, Jian, L, Bebbington, A, Jacoby, P, Nagarajan, L, Ravine, D, Woodhead, H
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age; Anticonvulsants; Anticonvulsants - administration & dosage; Anticonvulsants - adverse effects; Anticonvulsants - therapeutic use; Australia - epidemiology; Biological and medical sciences; Child; Child, Preschool; Children; Complications and side effects; Data Analysis; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Diseases; Divalproex; Drug Administration Schedule; Epidemiologic Methods; Epilepsy; Epilepsy - drug therapy; Female; Fractures; Fractures (Injuries); Fractures, Bone - chemically induced; Fractures, Bone - epidemiology; General aspects; Genetic aspects; Genotype & phenotype; Humans; Likert scale; Likert Scales; Medical sciences; Miscellaneous; Missing data; Mobility; Mutation; Narcotics; Neurology; Pediatric diseases; Prevention and actions; Prognosis; Public health. Hygiene; Public health. Hygiene-occupational medicine; Questionnaires; Rett syndrome; Rett Syndrome - drug therapy; Rett Syndrome - epidemiology; Risk factors; Risk reduction; Statistical Analysis; Valproic acid; Valproic Acid - administration & dosage; Valproic Acid - adverse effects; Valproic Acid - therapeutic use; Young Adult
• ISSN: 0003-9888; 1468-2044
• DOI: 10.1136/adc.2008.148932

Objectives Some associations between antiepileptic drugs (AEDs) and fracture risk have been reported in the general population. This study investigated the relationships between fracture risk and commonly used AEDs in Rett syndrome, a genetic disorder associated with intellectual and physical disability. Study design Cases (n=233) were sourced from the population-based Australian Rett Syndrome Database and longitudinal data were used. The Cox proportional hazard model was used to analyse relationships between fracture and prescribed AEDs, mobility, epilepsy diagnosis and genotype. Results After controlling for mobility, epilepsy diagnosis and genotype, use of valproate increased the risk of fracture threefold after at least 1 year (HR 3.56; 95% CI 1.85 to 6.82) and after 2 or more years (HR 3.02; 95% CI 1.90 to 4.80). There was a lesser increased risk (HR 1.99; 95% CI 0.99 to 4.02) with lamotrigine in the first year of use but not for subsequent years of use. Carbamazepine slightly decreased the risk (HR 0.60; 95% CI 0.35 to 1.02) after 2 or more years of use. Conclusions The effect of valproate on bone health should be considered when managing epilepsy in Rett syndrome. Multiple mechanisms could be contributing to this effect.