RANKL and Osteoprotegerin Levels in Response to Orthodontic Forces (2012)

Orthodontic tooth movement is mediated by interactions between PDL cells and those of the alveolus. One protein-the receptor activator nuclear factor kappa B ligand (RANKL)-is critical for osteoclastogenesis, and osteoprotegerin (OPG) is a decoy ligand that competitively inhibits RANKL. A higher RANKL/OPG ratio is associated with areas of bone resorption, while a lower ratio occurs in areas of bone deposition and homeostasis. There have been almost no clinical studies of RANKL and OPG expression in human subjects undergoing orthodontic tooth movement. The purpose of this study was to quantify changes in the levels of RANKL and of OPG expression in human gingival crevicular fluid in growing (adolescent) and non-growing (adult) patients in response to orthodontic force. Untreated adolescents (under 18 years of age) and adults (over 18 years of age) had a calibrated force applied across a left-right pair of maxillary premolars with a transpalatal spring (TPS). RANKL and OPG were measured in gingival crevicular fluid (GCF) sampled serially from the pressure and tension sides of maxillary premolars at 5 different time points: before placement of transpalatal spring, 1 day (24 hours) after TPS placement, 2 days (48 hours) after TPS placement, 5 days (120 hours) after TPS placement (TPS was then removed), and 3 days (72 hours) after TPS removal. RANKL and OPG expression was measured by the ELISA assay. Expectations were that (1) force would raise RANKL and diminish OPG, (2) force removal would reverse the RANKL-OPG levels, (3) strength and duration of force are associated with RANKL-OPG levels, (4) responses would exhibit considerable inter-individual variation, (5) the RANKL/ OPG levels will be higher in children due to general growth and bone remodeling in response to orthodontic forces, and (6) the RANKL/OPG levels will be lower in adults because no growth is occurring and osteoclastogenesis is triggered solely by orthodontic forces. Gingival crevicular fluid (GCF) volume increased significantly after applying force with the nickel-titanium coil spring. The volume remained elevated until the force was removed, and had not quite returned to baseline by 3 days (72 hours) following force removal. There were no significant differences found in the levels of GCF collected in regards to age, sex, or race. When evaluating the changes in gingival crevicular fluid in response to mechanical force, it appears that time is the significant factor regardless of the person's age, sex, or race. In general, both RANKL and OPG levels decreased significantly over the time while the spring was in place; however, the RANKL/OPG ratio increased over time. No significant differences were found in the levels of RANKL when comparing sex, age, and race. Higher levels of OPG were found in males. A linear decrease in OPG was seen in regards to age; therefore, adults have less OPG than their younger counterparts. Although not significant, African American levels of OPG were higher than Caucasians. Further research is needed to better describe what effect variations in individual RANKL and OPG expression have on orthodontic tooth movement.