Injectable RANKL sustained release formulations to accelerate orthodontic tooth movement.

BACKGROUND: Accelerating orthodontic tooth movement (OTM) through biologically effective methods, such as increasing osteoclast-mediated alveolar resorption, could effectively shorten treatment time. OBJECTIVE: To evaluate an injectable formulation containing receptor activator of nuclear factor kappa-B ligand (RANKL) on the OTM. MATERIALS AND METHODS: We fabricated a RANKL formulation from 100 µl of 100 µg/ml RANKL adsorbed on 10 mg of poly(lactic acid-co-glycolic acid) microspheres embedded in a 10 wt% aqueous hydroxyethyl cellulose carrier gel. We characterized these formulations for the rate of RANKL release, and then tested for bioactivity using in vitro cell culture. In vivo OTM studies were conducted using 15 week old male Wistar rats for 14 days. We injected the RANKL formulations palatal to the left maxillary first molar and accomplished OTM with a nickel-titanium (NiTi) coil spring applying 5-8 g force. Control groups involved the application of NiTi coil spring with and without placebo formulation. The outcome measure included the distance of tooth movement, bone volume fraction, tissue density, and root volume determined with micro-computed tomography. We determined the amount of osteoclast activity using tartrate-resistant acid phosphatase (TRAP) staining. RESULTS: These formulations were able to sustain the release of RANKL for more than 30 days, and the released RANKL showed a positive effect on mice osteoclast precursor cells (RAW 264.7). Reported injectable RANKL formulations were effective in accelerating OTM compared with other control groups, with 129.2 per cent more tooth movement than no formulation and 71.8 per cent more than placebo formulation, corresponding with a significant increase in the amount of TRAP activity. We did not observe any significant differences in root resorption between the groups. CONCLUSION: Our study shows a significant increase in OTM with injectable formulations containing RANKL.

Restless legs syndrome, neuroleptic-induced akathisia, and opioid-withdrawal restlessness: shared neuronal mechanisms?

Restlessness is a core symptom underlying restless legs syndrome (RLS), neuroleptic-induced akathisia, and opioid withdrawal. These three conditions also share other clinical components suggesting some overlap in their pathophysiology. Recent prospective studies demonstrate the frequent incidence of RLS-like symptoms during opioid withdrawal and supervised prescription opioid tapering. Based on the therapeutic role of µ-opioid receptor (MOR) agonists in the three clinical conditions and recent preclinical experimental data in rodents, we provide a coherent and unifying neurobiological basis for the restlessness observed in these three clinical syndromes and propose a heuristic hypothesis of a key role of the specific striatal neurons that express MORs in akathisia/restlessness.

The effect of alveolar decortication on orthodontically induced root resorption.

OBJECTIVE: To determine the effect of alveolar decortication on orthodontically induced root resorption. MATERIALS AND METHODS: A total of 24 male Wistar rats (14 week old) were used. The rats were randomly divided into one of the following three groups: group 1 (control group), orthodontic tooth movement (OTM) for 2 weeks; group 2, OTM for 2 weeks + two alveolar decortications (2AD); group 3, OTM for 2 weeks + four alveolar decortications (4AD). The first molar was moved mesially for 2 weeks. Micro computed tomography was used to analyze root volume. In addition, histological sections were stained with Tartrate Resistant Acid Phosphatase (TRAP) to quantify the osteoclast number. RESULTS: The buccal root volume in OTM + 4AD group was decreased by 8.92% and 6.11% when compared with the OTM-only group and OTM + 2AD group, respectively. Similarly, the other four root volumes in the OTM + 4AD group was decreased by 8.99% and 5.24% when compared with the OTM-only group and OTM + 2AD group, respectively. There was a decrease in buccal root density in the OTM + 4AD group by 4.66% and 3.56% when compared with the OTM-only group and the OTM + 2AD group, respectively. In addition, there was an increase in the number of osteoclasts by 195.73% and 98.74% in OTM + 4AD group in comparison with the OTM and OTM + 2AD group. CONCLUSIONS: The amount of orthodontically induced root resorption was positively correlated with the extent of surgical injury used to accelerate orthodontic tooth movement.