Therapeutic delivery of calcitonin to inhibit external inflammatory root resorption: I. Diffusion kinetics of calcitonin through the dental root.

Insertion of calcitonin into root canals of monkey teeth has been shown to inhibit external inflammatory root resorption and suppress inflammation. Regulation of this therapeutic event depends upon the rate of arrival (diffusion) of the hormone at sites of resorptive activity. In (he present study, the diffusion characteristics of calcitonin through the dental root in an extracted human-tooth model are described, and the role of cemenium in the diffusion process is also addressed. Root-canals were enclodontically prepared to form a reservoir for [125I]-calcitonin, and macerated to remove organic material from dentinal tubules. In teeth with intact cementum, an initial period of delay (4–5h) prior to the detection of calcitonin at the external tooth-root surface was followed by a rapid release- of the calcitonin during the first 10.5h (rate peaks at 6h). Slower, sustained releases of calcitonin through intact calcitonim were measured for the following 9 days. Removal of cementum, to expose “smear-free” dentine, resulted in an earlier efflux of calcitonin (2h) at external tooth surfaces and increased amounts of calcitonin release over 9 days. Biphasic deliver)’of calcitonin by such internal diffusion mechanisms suggests that loss of cementum will enhance therapeutic availability, while prolonged delivery to intact external dental-root surfaces following early intra-canal placement may also be useful for the therapeutic prevention of external in-llammatory root resorption.O. W. Wiebkin, S. C. Cardaci, G. S. Heithersay, A. M. Pierc

Therapeutic delivery of calcitonin to inhibit external inflammatory root resorption: II. Influence of calcitonin binding to root mineral.

Experimentally-induced external inflammatory tooth-root resorption can be inhibited by therapeutic doses of calcitonin. Such doses can be delivered by an intrinsically slow diffusion pathway, from a reservoir in endodontically-clebrided root canals, via the dentinal tubules. While the kinetics of this journey have been followed in an earlier report, the binding characteristics of calculation to the tooth mineral, which will be responsible, in pan, for these kinetics, have not been reported before. The current study examines the binding potential of calcltonin to root mineral and addresses the potential role of non-specific binding proteins. A modified Scatchard plot indicated that a simple non-reactive type of ligancal binding exists between calcitonin and root mineral, represented by a small number of identical binding sites. This interaction is both strong and reversible. Furthermore, it appears to be time-dependent with more time being required for the residual ligands to interact with the diminishing numbers of free calcitonin-binding sites. While preloaded [125 I]-calcitonin could be incompletely (75–91%) displaced from dental-root material by non-radioactive calcitonin, its release was slow over 23h. Calcitonin was four times as effective1 as bovine-serum albumin in competing for common “calcitonin binding sites” on macerated dental-root material. Thus, even in the presence of extraneous protein, calcitonin will bind tightly but re-versibly to total-root. material, making it a good candidate for therapeutically protracted delivery to external root surfaces from root canals.O. W. Wiebkin, S. C. Cardaci, G. S. Heithersay, A. M. Pierc