Summary
Four groups (A, B, C, D) of 21-day-old rats were weaned onto a low phosphorus rachitogenic diet and maintained for 149 days. Groups A, B and C received 4 IU oral ergocalciferol (vitamin D2) supplements in arachis oil every second day. Groups B and C received oral diphenylhydantoin (DPH, 6 g/kg diet; up to 500 mg/kg body weight/day) for 116 and 21 days respectively. At the end of the experiment the width of the osteoid seams in the long term DPH group B were similar to those in the rachitic control group D and both were significantly wider than those in groups A and C (P<0.01).
The overall mean serum Ca levels of groups B and D were each significantly lower than those of group A (P<0.005). The serum Ca levels of the group C rats before drug administration were not different from those of group A, but were significantly reduced after administration of DPH (P<0.005).
The reduced serum calcium levels of the rats in groups B and D support the histological evidence of osteomalacia in these animals. The reduced serum calcium levels, without increased osteoid in the group C rats, after DPH administration indicate a short term effect of the drug. This work supports the theory that chronic DPH treatment can antagonize the antirachitic effect of calciferol and so produce “anticonvulsant osteomalacia” in humans and animals.
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Harris, M., Rowe, D.J.F. & Darby, A.J. Anticonvulsant osteomalacia induced in the rat by diphenylhydantoin. Calc. Tis Res. 25, 13–17 (1978). https://doi.org/10.1007/BF02010745
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DOI: https://doi.org/10.1007/BF02010745