The effect of local administration of phenytoin on fracture healing: an experimental study

The antiepileptic drug phenytoin (Diphenylhydantoin) has been documented to have a beneficial effect on wound healing; its effect on fracture healing, however is still unclear. In an attempt to evaluate any potential benefits phenytoin may have on fracture healing, a prospective study was undertaken combining histology, histomorphometry and radiology, in which the effects of locally administered phenytoin were analysed. Twenty-four Wistar strain rats of 8-9 months age were assigned into two groups of 12 each (matched for age, sex and weight). In the study group, phenytoin 20 mg/kg was administered through a 24 gauge needle directly on to the fracture site every 72 hours, while in the control group an equivalent volume of normal saline was administered at similar intervals. At 28 days radiographic and histological analysis was done, the scoring for which did not show any statistical difference between the control and test animals. Histomorphometric analysis of the callus however, showed that the total periosteal callus on either side of the central bridging callus was mineralised to a greater extent in the phenytoin group animals as compared to the control group animals (p = 0.011). After analysing our data, we concluded that phenytoin does have an influence in fracture healing, albeit small, which is primarily on the hard callus region. The hard callus region is the high oxygen tension region and the first region to differentiate. It appears that the effect of phenytoin is probably exerted at the early mesenchymal differentiation stage. However our preliminary work shows that the effect is small and it is not justifiable at this stage to advocate the use of phenytoin clinically to augment fracture healing.