Effects of 1‐hydroxyethylidene‐1, 1‐bisphosphonate (HEBP) on the formation of dentin and the periodontal attachment apparatus in the mouse

Abstract

The effects of the bisphosphonate HEBP on dentin formation and the structural relationship between the dentin and the developing periodontal attachment apparatus have been studied in the continuously growing mouse incisor. It was observed that HEBP (in doses greater than or equal to 8 mg P/kg b.w/day) not only inhibited the deposition of mineral crystallites in newly formed dentin matrix, but also entirely prevented the formation of a layer of acellular root cementum. It was further noticed that the drug interfered with the deposition of 3H-serine-containing substances at the predentin-dentin border. This was not always accompanied by an inhibition of dentin mineralization, thereby suggesting that 3H-serine-containing proteins (presumably phosphoproteins) do not play a critical role in the deposition of mineral layers onto previously formed ones. The absence of a cementum layer did not prevent the developing periodontal ligament from establishing matrix-to-matrix connections with the root-analogue dentin. Collagen fibrils of the ligament intermingled with those of the mantle dentin, which in contrast to teeth not exposed to the drug were clearly visible and not masked by electron-dense matrix components. Finally, it was found that the drug had distinct effects on the formation of root-analogue and crown-analogue dentin. Whereas during the course of the experiment the odontoblasts along the crown-analogue aspect of the tooth continued to produce circumpulpal dentin matrix, those along the root-analogue aspect of the tooth did so only when the mantle dentin layer had been mineralized prior to HEBP administration. This phenomenon is interpreted as being indicative of fundamental differences between the formation of crown and root dentin.

The Distribution of Magnesium in Developing Rat Incisor Dentin

“…These findings further substantiate the notion that intrinsic differences exist in the rodent incisor between the ERD and CRD with respect to formation and mineralization of dentin (Beertsen et al, 1985;Beertsen and Niehof, 1986;Steinfort et al, 1989Steinfort et al, , 1990.…”

Dentinogenesis

“…Thus, Beertsen and colleagues found differences in reactivity to bisphosphonate, in amino acid incorporation, as well as differences with respect to phosphoprotein distribution (Beertsen et al, 1985;Beertsen and Niehof, 1986;Steinfort et al, 1989). In bovine incisors, phosphoproteins, present in the crown, could not be detected in the root (Takagi et al, 1988).…”

Immunocytochemical Study of Amelogenin Deposition during the Early Odontogenesis of Molars in Alendronate-treated Newborn Rats

“…Although several studies have suggested that bisphosphonates do not adversely affect the osteoblast activity (Sato et al 1991;Nii et al 1994;Rodan and Fleisch 1996;Evans 2002), cells other than osteoclasts may also be affected by bisphosphonates in other mineralized tissues. It has also been reported that bisphosphonates act as inhibitors of mineralization in bone (Francis 1969;King et al 1971;Schenk et al 1973) and tooth (Reynolds et al 1973;Beertsen et al 1985;Ogawa et al 1989;Takano et al 1998;Sakai et al 1999;Jayawardena et al 2002). Indeed, administration of bisphosphonates at high and successive doses has been shown to affect mineralization of both dentin and enamel (Simmelink 1987;Izumi 1989;Ohya et al 1989;Fejerskov et al 1990;Weile et al 1990Weile et al ,1993Fouda et al 1991;Wakamatsu 1991;Takano et al 1998).…”