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

Abstract: DEVELOPMENTAL DISTURBANCES OF CEMENTUM INDUCED BY 1-HYDROXYETHYLIDENE-1,1-BISPHOSPHONATE (HEBP) Experimental studies on ratsI. ALATLI BURTDivision of Oral Pathology at the Department of Oral Diagnosis and Center for Oral Biology,Novum, Karolinska Institute, Stockholm, Sweden By studying the mechanism(s) behind experimentally induced developmentaldisturbances 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 fewstudies in which its development has been experimentally altered. Recently it has beenreported from studies on continuously growing mouse incisors that the formation of acellularcementum could be completely inhibited by repeated injections of l-hydroxyethylidene-l,l-bisphosphonate (HEBP). The bisphosphonate HEBP has a strong affinity for the mineralizedtissues and has proven to be a potent inhibitor of bone mineralization and resorption. Thegeneral purpose of the present thesis was to study the effects and possible mechanisms ofaction of HEBP on cementum formation in rooted teeth such as rat molars, and at the sametime gain information about the normal formation of cementum. Single or triple injections of HEBP at a dose corresponding to 10 mg P/kg body weightwere 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 tensilestrength evaluation and immunohistochemistry were used to study the development ofHEBP-induced defects. Single or triple exposures to HEBP at the dose given inhibited the mineralization ofradicular dentin and interfered with the formation of acellular cementum. Administration ofHEBP during root development led to the formation of a tissue layer on the unmineralizedroot dentin surface, which was called "atypical hyperplastic cementum". It was found that thisHEBP-induced atypical hyperplastic cementum was topographically similar to normal cellularcementum. Immunohistochemical studies indicated that the formation of both the atypicalhyperplastic cementum and the normal cellular cementum was associated with a separation ofinner and outer layers of the epithelial root sheath. HEBP also interfered with the normaldevelopment of the tensile strength of the periodontal ligament and with the growth of theroot. The presence of atypical hyperplastic cementum increased the spontaneous resorption ofthe root. This resorption was further increased when the teeth were exposed to an orthodonticforce. The results from this study indicate that the formation of acellular cementum isassociated with the initial mineralization of radicular dentin.The permanent inhibition of allsubsequent formation of acellular cementum by a single injection of HEBP suggests that thisdrug stops the apically directed propagation of the differentiation to cementum-forming cells.Keywords: dental cementum, dentin, rat molar, bisphosphonate, mineralization, scanningelectron microscopy, immunohistochemistry, epithelial root sheath.Repro Print AB, Stockholm 1996ISBN 91-628-2040-0