Odontoclastic root resorption is a significant clinical issue in relation to orthodontic tooth movement, and resorption of the roots of primary teeth is an intriguing biological phenomenon. The functional coordination of the OPG/RANKL/RANK system seems to contribute not only to alveolar remodeling, but also to resorption during orthodontic tooth movement and physiological root resorption. Serum OPG and s-RANKL are related to regulation of bone homeostasis by the OPG/RANKL/RANK system, and determination of their concentrations might be useful for predicting the rate of bone remodeling during orthodontic tooth movement, the net effect between bone remodeling and root resorption, and the degree of root resorption. It is therefore rational to speculate that a study of the levels of OPG and s-RANKL in blood and GCF, in relation to the degree of root resorption during orthodontic tooth movement, using healthy experimental animals and a carefully planned and organized experimental design, may be able to answer this intriguing question. (J. Oral Sci. 50, 367-376, 2008)