Effects of chronic administration of sodium diphenylhydantoin ('Dilantin') on bones and teeth of the rat and hamster: a preliminary study.

Male Charles River rats, 31-days old, received i.p. injection of sodium diphenylhydantoin (DPH), 100 mg/kg in 0.9% NaCl, once daily for 26-27 days before death. Male Syrian hamsters, 40-days-old, received similar injections of DPH, 25 mg/kg for 46 days, no treatment for 39 dyas, then DPH FOR A FURTHER 17 DYAS BEfore sacrifice. All rats receiving DPH gained less weight than the controls, and more than 50% displayed acute neurotoxic reactions to the drug; hamsters were not so affected. Morphology and composition of caudal vertebrae, teeth, and jaws from control and DPH-rats were compared on the basis of measurements on radiographs and gross specimens, histological investigation, and determined of % dry volumes of ash, volatile inorganic component, lipid, and organic matrix. DPH-bertebrae were smaller and showed impaired osteogenesis; but chondrogenesis was similar to controls. Overall tail length was similar in both animal groups because caudal intervertebral spaces were wider in DPH-rats, compensating for reduced longitudinal growth of corresponding vertebrae. Incisors were smaller and third molar roots shorter in DPH-rats. In DPH-hamsters the attachment of the periodontal ligament to maxillary incisors was deranged. DPH administration did not change the composition of rat bone or teeth. Densities of dry bones and teeth were in accord with their composition. Possible modes of action of DPH are discussed. Species differences in response of mineralized tissues to DPH administration are emphasized in relation to reports of rickets and osteomalacia in patients on long term DPH therapy.