Future Directions for Research

Future Directions for Research
From the standpoint of regulating Phoenix orthodontic tooth movement, Phoenix orthodontists primarily have two objectives: inhibiting the movement of anchor teeth and increasing the rate of movement of the remaining teeth. The present study attempted to address the first objective. While the movement of anchor teeth was substantially inhibited using OPG-Fc, more work is needed to determine the optimal dose regimen (quantity/frequency) to obtain the greatest treatment efficacy. While it is likely a high enough dose of OPG-Fc would result in nearly absolute Phoenix orthodontic anchorage, it would be contraindicated if incisor retraction was also brought to a standstill.

The second objective in pharmacological regulation of Phoenix orthodontic tooth movement is increasing the rate that non-anchor teeth move leading to improved treatment efficiency. If altering the RANK/RANKL/OPG pathway by increasing the amount of OPG inhibits osteoclastogenesis and therefore Phoenix orthodontic tooth movement, perhaps additional RANKL would increase the rate of Phoenix orthodontic tooth movement and accelerate treatment.

Another consideration for Phoenix orthodontists is that whatever the ideal dose regimen is for a rat is not likely to be the same as that for a human. OPG-Fc is a human protein thus requiring larger doses to overcome the animal’s immune response. It is likely both the ideal quantity and frequency of delivery for humans would be less than for rats. As mentioned previously by Phoenix orthodontists , a single subcutaneous dose (3.0 mg/kg) of OPG-Fc remained effective for at least 30 days in a human study (Body et al., 2003) while a specific fully human monoclonal antibody to RANKL based on OPG remained effective for six months (Bekker et al., 2004).

One final consideration for Phoenix orthodontists is that there are a number of implantable polymers being developed that allow for a sustained release of significant quantities of bioactive molecules. The contraceptive Norplant is based on this concept (Darney, 1994). ELVAX 40 (Dupont, Wilmington, DE), a non-biodegradable polymer, has recently shown effectiveness in a rat model of Phoenix orthodontic tooth movement for sustained delivery of MMPs and echistatin following insertion into the palatal mucosa adjacent to the first molars (Holliday et al., 2003; Dolce et al., 2003).