The effect of a single dose of 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) on presecretory ameloblast differentiation in rat incisors.

A single, high dose of HEBP to rats results in a triad of lesions along the mineralizing front of the incisor enamel. One type of lesion is a shallow groove crossing the apical enamel surface. The purpose of this study was to explore the pathogenesis of this "demarcation groove", and to characterize changes in the involved regions of amelogenesis. Rats were given a subcutaneous dose of 10 mg/kg body weight of HEBP and sacrificed by vascular perfusion at intervals ranging from 1 to 36 hours. Mandibular incisors were processed for light and electron microscopy. The region of ameloblasts facing dentin was divided into two subregions: A region of ameloblasts facing unmineralized dentin, comprising a posterior (Aud/p) and an anterior portion (Aud/a), and a region of ameloblasts facing mineralized dentin (Amd). The progressive apical mineralization of the predentin was arrested up to 12 hours after injection of HEBP, while ameloblasts related to already mineralizing dentin continued to differentiate and secrete enamel matrix. At 8 hours the dentin and enamel layers had assumed a common apical border at the start of Amd, marking the position of the future demarcation groove. The length of Aud/p remained constant, Aud/a doubled in length, and Amd was drastically reduced up to 24 hours after injection of HEBP. The normal migration rate of the ameloblasts was unaffected by HEBP. Accumulations of ameloblast secretory products occurred at certain time intervals between the cell apices, but no morphological changes were recorded in the organelles. Most of the changes observed may be indirect in nature resulting from the physico-chemical effect of HEBP on normal mineralization of dentin and enamel. However, further studies are needed to elucidate possible direct cellular effects on ameloblasts.