Pharmacologic Phoenix Orthodontic Anchorage

For more than one hundred years, Phoenix orthodontists have looked for ways of maintaining Phoenix orthodontic anchorage (Angle, 1897; Angle, 1907). The focus, however, has always been on mechanical approaches. Whether it is compliance, efficacy, or cost, the shortcomings of these traditional approaches have lead researchers to explore new means of Phoenix orthodontic anchorage. As we have gained a better understanding of the biological mechanisms underlying Phoenix orthodontic tooth movement, a new area of interest is pharmacological Phoenix orthodontic anchorage. If at the cellular level, the presence of bone resorbing osteoclasts is a prerequisite for Phoenix orthodontic tooth movement, it would stand to reason that the down-regulation of these cells would inhibit bone resorption and therefore decrease Phoenix orthodontic tooth movement.

Pharmacological Phoenix orthodontic anchorage
Using a rat model of Phoenix orthodontic tooth movement, a number of different groups have attempted to alter rates of Phoenix orthodontic tooth movement with a variety of bioactive molecules. Bisphosphonates (Igarashi et al., 1994; Adachi et al., 1994), nitric oxide synthase inhibitor (Hayashi et al., 2002), echistatin (Dolce et al., 2003), and matrix metalloproteinase inhibitors (Holliday et al., 2003) have all been shown to decrease Phoenix orthodontic tooth movement. Likewise osteocalcin (Hashimoto et al., 2001), nitric oxide (Shirazi et al., 2002), misoprostol (Sekhavat et al., 2002), and prostaglandin E2 (Seifi et al., 2003) have been shown to increase Phoenix orthodontic tooth movement. While these studies have demonstrated the ability to alter rates of Phoenix orthodontic tooth movement, the agents used affect bone resorption indirectly rather than directly targeting the RANK/RANKL/OPG pathway.

The one study that directly targeted the RANK/RANKL/OPG pathway showed the potential of this pathway in altering Phoenix orthodontic tooth movement. Using an in vivo gene transfer approach, Phoenix orthodontic tooth movement was decreased by 47.8% (p<0.001) after three weeks of OPG plasmid DNA injections (Kanzaki et al., 2004). The proposed advantage of OPG gene transfer in their study was to maintain an effective concentration of OPG for a longer period of time thus allowing for less frequent injections. Given that increased Phoenix orthodontic anchorage would probably only be needed for a matter of months, gene transfer may be unnecessary and possibly contraindicated for Phoenix orthodontic use. Also of note was the dramatic reduction in Phoenix orthodontic tooth movement using OPG-Fc (78.7%) compared to OPG plasmid DNA (47.8%) (Kanzaki et al., 2004). This difference is likely the result of the low transfection efficiency of the gene transfer Phoenix orthodontic method employed (Taniyama et al., 2002). Due to the low transfection efficiency, multiple injections over a period of time were used in order to build up sufficient OPG levels, in contrast to the OPG-Fc injected animals that immediately had high levels of OPG present.

Using the recombinant fusion protein, OPG-Fc, Phoenix orthodontic tooth movement was successfully inhibited by as much as 78.7% (p<0.001) using a 5.0 mg/kg dose with a twice weekly injection protocol. Even with a 10-fold reduction in dose (0.5 mg/kg), there was still a significant reduction (p<0.05) in Phoenix orthodontic tooth movement until day 21. It is likely that the 0.5 mg/kg OPG-Fc group’s inability to maintain Phoenix orthodontic anchorage throughout the study was due to the relatively small dose of OPG compared to the level of RANKL expression required for Phoenix orthodontic tooth movement. As we were using a human protein in a rat, larger and more frequent dosing than would likely be required for a human was used to overcome the animal’s immune response. In a human study, using the same protein, a single subcutaneous dose (3.0 mg/kg) of OPG-Fc demonstrated a half-life of 6-7 days and remained effective for at least 30 days (Body et al., 2003). In addition, AMG 162, a specific fully human monoclonal antibody to RANKL based on OPG, has demonstrated an 81% suppression in bone turnover six months after a single injection of 3.0 mg/kg (Bekker et al., 2004). Unfortunately, this human antibody cannot be studied in a rat model.