Bone changes induced by diphenylhydantoin in chicks on a controlled vitamin D intake

Florid rickets developed in chicks receiving doses of diphenylhydantoin analogous to doses used in humans as anticonvulsants, vitamin D3 being given in amounts sufficient for normal bone mineralization in controls. The changes in the bones were directly related to the dose of diphenylhydantoin and inversely related to the dose of vitamin D3. Bone mineralization was assessed by roentgenography, histological examination, microradiography, and measurement of bone ash. Of these methods, roentgenography was the least sensitive. Rachitic changes were detectable by light microscopy and microradiography in chicks whose skeletons appeared normal roentgenographically. Roentgenographic evidence of rickets became detectable only when the rickets was far advanced. Rickets developed at serum levels of diphenylhydantoin similar to those found in patients taking anticonvulsant medication.