Valproate and risk of fracture in Rett syndrome.
OBJECTIVE
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.


METHODS
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.
Leonard
H
H
Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, West Perth, Western Australia. hleonard@ichr.uwa.edu.au
Downs
J
J
Jian
L
L
Bebbington
A
A
Jacoby
P
P
Nagarajan
L
L
Ravine
D
D
Woodhead
H
H
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001315:Australia / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004812:Epidemiologic Methods; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D050723:Fractures, Bone / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015518:Rett Syndrome / Q000188:drug therapy* / Q000453:epidemiology; D014635:Valproic Acid / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D055815:Young Adult
D000927:Anticonvulsants; D014635:Valproic Acid