The effects of phenytoin on calcium uptake in osteoblastic cells

The effects of phenytoin (diphenylhydantoin, DPH) on calcium uptake in osteoblastic cells were studied to elucidate the potential mechanism of action of this antiepileptic drug on bone metabolism. Preincubation of the human osteoblastic osteosarcomal cell line, SaOS-2, and normal rat osteoblastic cells with DPH decreased basal calcium uptake. This inhibition occurred at DPH doses from 0.1 to 50 micrograms/ml. Parathyroid hormone (PTH) and prostaglandin E2 (PGE2) increased calcium uptake in the SaOS-2 cell line. Following preincubation with DPH, calcium uptake in cells treated with PTH or PGE2 did not exceed control levels. However, significant increases in the PTH- or PGE2-treated + DPH-pretreated cells compared to DPH pretreatment alone were still observed. These studies indicate that DPH induces decreases in osteoblastic calcium influx and they add further information on the possible mode of action of this drug on bone.