Developmental disturbances of cementum induced by 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) : experimental studies on rats

By studying the mechanism(s) behind experimentally induced developmental disturbances of a tissue, it may be possible to gain information about its normal development. Cementum seems to be the least understood of the dental tissues, and there are very few studies in which its development has been experimentally altered. Recently it has been reported from studies on continuously growing mouse incisors that the formation of acellular cementum could be completely inhibited by repeated injections of l-hydroxyethylidene-l,l-bisphosphonate (HEBP). The bisphosphonate HEBP has a strong affinity for the mineralized tissues and has proven to be a potent inhibitor of bone mineralization and resorption. The general purpose of the present thesis was to study the effects and possible mechanisms of action of HEBP on cementum formation in rooted teeth such as rat molars, and at the same time gain information about the normal formation of cementum.

Single or triple injections of HEBP at a dose corresponding to 10 mg P/kg body weight were given subcutaneously in the back of the neck of 10- to 20-day-old Sprague-Dawley rats. Light and scanning electron microscopy, histochemistry, histomorphometry, ultimate tensile strength evaluation and immunohistochemistry were used to study the development of HEBP-induced defects.

Single or triple exposures to HEBP at the dose given inhibited the mineralization of radicular dentin and interfered with the formation of acellular cementum. Administration of HEBP during root development led to the formation of a tissue layer on the unmineralized root dentin surface, which was called "atypical hyperplastic cementum". It was found that this HEBP-induced atypical hyperplastic cementum was topographically similar to normal cellular cementum. Immunohistochemical studies indicated that the formation of both the atypical hyperplastic cementum and the normal cellular cementum was associated with a separation of inner and outer layers of the epithelial root sheath. HEBP also interfered with the normal development of the tensile strength of the periodontal ligament and with the growth of the root. The presence of atypical hyperplastic cementum increased the spontaneous resorption of the root. This resorption was further increased when the teeth were exposed to an orthodontic force.

The results from this study indicate that the formation of acellular cementum is associated with the initial mineralization of radicular dentin. The permanent inhibition of all subsequent formation of acellular cementum by a single injection of HEBP suggests that this drug stops the apically directed propagation of the differentiation to cementum-forming cells.