While Phoenix orthodontic tooth movement models, dosing regimens, and lengths of studies varied, it appears that 5.0 mg/kg OPG-Fc produced the greatest inhibition (78.7%) in molar Phoenix orthodontic tooth movement of any study to date (Table 2).  The next best bioactive molecule appeared to be bisphosphonate, which inhibited Phoenix orthodontic tooth movement by 60.3% using every other day injections. 

The mechanism of action for bisphosphonate differs from OPG in that it deposits in the hydroxyapatite on the bone surface thus inhibiting osteoclast activity through internalization and decreasing quantity by accelerating apoptosis (Ruggiero et al., 2004).  While bisphosphonates have shown beneficial effects in reducing skeletal complications such as pain and pathological fracture in patients with bone metastases (Diel et al., 1998; Powles et al., 2002; Saad et al., 2002), they have recently contributed to a controversy due to some serious side effects.  Bisphosphonates have also been shown to inhibit angiogenesis, leading multiple groups to report an increased incidence of osteonecrosis in patients taking these medications (Ruggiero et al., 2004; Cheng et al., 2005; Melo and Obeid, 2005).

Matrix metalloproteinase (MMP) inhibitors have a different mode of action than either OPG or bisphosphosphonates.  During bone remodeling, components of the extracellular matrix are degraded and removed while new components are synthesized and deposited.  MMPs appear to play a key role in the degradation process (Delaissé et al., 2000).  This family of more than 25 enzymes regulates biological processes such as development, morphogenesis, and wound healing (Woessner, 1991).  A number of studies have shown that interstitial cleavage of type I collagen as a result of MMPs triggers bone resorption (Holliday et al., 1997; Zhao et al., 1999; Lin et al., 2003).  Although MMP inhibitors do inhibit osteoclasts and bone resorption, their affects appear to be less than those of OPG or bisphosphonates.  This is likely due to redundancy in systems as arginine-glycine-aspartic acid (RGD) peptides can substitute for MMP activity resulting in bone resorption (Holliday et al., 2003).

One of the advantages of the mesial molar movement model that was used in the present study is that incisor retraction can also be measured.  This allowed for evaluation of the effects of OPG on neighboring teeth.  While there was a decreased rate of incisor retraction with increased levels of OPG, the overall treatment efficacy as measured by the ratio of incisor retraction to molar Phoenix orthodontic anchorage loss was greatly improved in the 5.0 mg/kg OPG-Fc injected group (5.2:1) compared to controls (2.3:1).  As differentially altering rates of Phoenix orthodontic tooth movement is the ultimate goal from a Phoenix orthodontic standpoint; this result was encouraging. 

Arizona Dental Association