Inhibition of cartilage growth by the anticonvulsant drugs diphenylhydantoin and sodium valproate.
Anticonvulsant-treated epileptic children have reduced growth and show skeletal deformities similar to those seen in hypoparathyroidism. In view of the crucial role of chondrocytes in endochondral bone growth we investigated the effects of anticonvulsant drugs on cartilage growth in rats. Rats were injected i.p. with diphenylhydantoin (PHT) or sodium valproate (dipropyl acetate; DPA), or were thyroparathyroidectomized (TPX) to render them deficient in parathyroid hormone (PTH). Cartilage growth, measured as the increase in thickness and cross-sectional area of the femoral epiphysis and the mandibular condyle cartilage, was significantly reduced in the PHT and TPX groups compared with control animals receiving the drug vehicle alone or a 'sham' TPX operation. The cellularity of the cartilage was reduced in all three treatment groups, but DPA had less effect than PHT or TPX. The similarity in effect between TPX and anticonvulsant treatment suggest the drugs may also interfere with the regulation of chondrocyte activity proliferation and matrix synthesis are reduced by anticonvulsant therapy, and that this contributes to the pathogenesis of abnormal skeletal growth in anticonvulsant-treated children.
D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D002452:Cell Count; D008297:Male; D010281:Parathyroid Hormone / Q000502:physiology; D010672:Phenytoin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014635:Valproic Acid / Q000494:pharmacology*
D010281:Parathyroid Hormone; D014635:Valproic Acid; D010672:Phenytoin