Very few reports have been published about the effects of diphosphonates on the cells and tissues of developing teeth. The present study was designed to investigate possible morphological changes in ameloblasts and odontoblasts and relate these changes to defects in the enamel surface of erupted teeth. Young rats were injected subcutaneously with single or multiple doses of HEDP or Cl2MDP (10 mg P/kg b.w.). Light microscopic examination of developing maxillary first molars showed that single injections of HEDP or Cl2MDP induced subameloblastic cysts between the secretory ameloblasts and the developing enamel. The ameloblastic lining of the cysts contained numerous calcified deposits. A few days after injection, hypoplasias were seen in the enamel in areas previously occupied by cysts. In the erupted teeth, scanning electron microscopic examination revealed enamel hypoplasias which were mainly localized on the mesial sides of the cusps. In addition to the previously mentioned disturbances, multiple injections resulted in more extensive cysts, some of which contained non-mineralized enamel matrix. Inhibition of the mineralization of dentin and alveolar bone was also noticed.

Activation of the protein kinase C (PKC)-related signal transduction system has been associated with phenotypic expression in a wide variety of cell types. In in vitro studies, it has often been activated by relatively small increases in the Ca2+ concentration ([Ca2+]) in the medium. The studies reported here explored the hypothesis that localized increases in the extracellular [Ca2+] and activation of the PKC-related pathway may be involved in early dentin and enamel formation. Whole-head, freeze-dried sections through the developing molars of 5-day-old rats were evaluated by methods that localized non-crystalline Ca2+. Immunohistochemical methods were adapted for use with the freeze-dried sections, and two monoclonal antibodies were used to localize PKC alpha in the formative cells of the developing teeth. Low concentrations of extracellular Ca2+ were observed in the early, unmineralized dentin in the area of ameloblast differentiation. Increased concentrations occurred at the point of initial dentin mineralization, immediately before the beginning of enamel matrix deposition. PKC alpha was localized in the differentiating odontoblasts, at the beginning of dentin matrix deposition. It was intensely localized in the distal borders of the pre-ameloblasts, and appeared to redistribute in the cells during ameloblast differentiation. These observations suggest that local increases in the extracellular [Ca2+] and the PKC signal transduction pathway may be involved in key inductions in the early stages of dentin and enamel formation.

Fifty-four cylinders (2.8 mm in diameter) machined from hot isostatically pressed titania (TI) and titania-hydroxyapatite (TI/HA-15vol %) sintered at 925°C, as well as commercially pure titanium (c.p.Ti), were implanted in the femoral cortical bone of New Zealand white rabbits for 1, 3 and 12 months. The shear strength between bone and implant was measured by a push-out test. The TI/HA composite showed a significantly higher bonding strength to bone compared to c.p. Ti at all times, while no differences were observed between TI and c. p. Ti at 1 and 3 months after implantation. Titania-based materials had a significantly higher bonding strength than that of c.p.Ti one year after implantation. The results indicate that bioactivity of HA in TI/HA composite contributes to the early bone apposition reflected by high bonding strength, while the stability of the oxide, determines the development of long-term bonding strength. Both effects may be explained by the level and type of ions released from the ceramic implant. HA has a positive conduction to bone ingrowth while TI has a limited interaction to the bone apposition due to the extraordinary low ion release in vivo. Under light microscopy, similar patterns of bone implant interfaces were seen from titania-based materials and c.p.Ti in 3-month samples, indicating high biocompatibility of these materials. However, histological evaluation by light microscope cannot identify the differences between physical contact and chemical bonding of implant-bone interface, and thus does not give information on bonding mechanism and the level of shear stresses developed.

Effects of phosphonoformic acid and 1-hydroxyethylidene-1,1-bisphosphonate(HEBP)on , . distribution of tetracycline in the developing rat molar Fouda N, Kttt I A. Hammarstrom L: Effects of phosphonoformic acid and l-hydroxyethylidene-l,l-bisphosphonate (HEBP) on distribittion of tetracycline in the developing rat tnolar. Scand J Dent Res 1992; 100; 257-65. Tetracycline was used as a marker to study the effect of phosphonoformic acid and l-hydroxyethylidene-l,l-bisphosphonate (HEBP) on the mineralization of the developing dental hard tissues. Groups of young rats were given a single subcutaneous injection of tetracycline and at the same time were injected with a single dose of either phosphonoformic acid or HEBP (10 mg P/kg b.w.). Alternatively, rats were injected with the tetracycline after different time intervals from the phosphonate injection. Rats were sacrificed at intervals ranging from 1 to 4 days. Frozen-sections were obtained at the level of the maxillary first molar and prepared for light and fluorescence microscopy. The results of the present study indicate that the distribution pattern of tetracycline in the developing dental hard fissues is greatly affected by the pathologic changes induced by phosphonoformic acid and HEBP. Both drugs caused similar changes in the pattern of tetracycline uptake in the developing enamel. There seems to be a direct relation between the presence of developmental defects of enamel and the degree of discoloration induced by tetracycline. Aberrations in the mineralization of dentin were caused only by HEBP. As demonstrated by this study, HEBP is capable of inducing a provisional inhibitory effect on dentin mineralization.

– The effect of a single subcutaneous injection of different dosages of phosphonoformic or phosphonoacetic acid on the developing dental tissues of the rat molar was studied. The substances were injected at different rat ages and effects on the developing teeth were analyzed by means of histochemistry of frozen sections and scanning electron microscopy. Molars of rats injected at the age of 10 or 15 days showed no pathologic changes. Administration of phosphonoacetic acid in a dosage of 10 or 20 mg P/kg b.w. had no demonstrable effect on the dental tissues in any of the animals. Phosphonoformic or phosphonoacetic acid in a dosage of 10 or 30 mg P/kg b.w. respectively induced subameloblastic cysts 24 h after injection to 4–7‐day‐old rats. The cysts were mainly localized on the mesial sides of the cusps under ameloblasts in the late secretory stage. Calcified depositions were seen in the ameloblastic layer lining the cystic cavities. A thin zone, the staining of which indicated a high mineral content, was seen in. the outermost enamel layer under the cysts, A few days later, enamel hypoplasias were seen in areas previously occupied by cysts. A lightly stained line was observed in the enamel matrix demarcating the amount of enamel matrix formed before and after the injection. Hypoplastic lesions were also noted in the enamel surface of newly erupted molars. These findings suggest that the two injected monophosphonates can induce pathologic changes in the developing enamel organ and hypoplasias in the enamel.