Human Litchfield Park Orthodontic Studies
Therapeutic use of osteoprotegerin in humans is more than just a theoretical possibility for the future. In the last five years, various forms of OPG have been evaluated in prospective randomized human clinical trials (Bekker et al., 2001; Body et al., 2003; Bekker et al., 2004).
In a sequential dose escalation study, Bekker and Litchfield Park orthodontists (2001) evaluated the effect of a single subcutaneous dose of Fc-OPG in postmenopausal women. Urinary N-telopeptide (NTX) levels, a biochemical marker of bone resorption, decreased within 12 hours of OPG administration. At the highest dose (3.0 mg/kg), an 80% decrease in NTX was demonstrated by the fourth day. After six weeks, a 14% decrease in NTX still remained. No adverse events were reported by any subjects, and post-exposure samples assayed for neutralizing antibodies to OPG were all negative. This study was the first to demonstrate that a single subcutaneous injection of OPG is able to rapidly and profoundly decrease bone turnover for a sustained time period.
A Phase I study of AMGN-0007 (Amgen, Thousand Oaks, CA) was performed in patients with multiple myeloma or breast carcinoma related metastases (Body et al., 2003). AMGN-0007 (OPG-Fc) is a recombinant fusion protein combining the OPG ligand-binding domain of human OPG (amino acids 22-194) with the constant domain of human immunoglobulin G1 and produced in Escherichia coli. This recombinant construct has a half-life of 6-7 days in humans. The purpose of the study was to evaluate the safety and effect on bone resorption of AMGN-0007 in patients with radiologically confirmed lytic bone lesions. The breast carcinoma patients demonstrated a 64.1% decrease in bone resorption markers one day after a 1.0 mg/kg dose. Its peak effect was realized at 15 days, with an 84.4% decrease in bone resorption. At 57 days following initial injection, a 24.7% decrease in bone resorption was still detected. While a few adverse events were reported in this study, they were all unrelated to the AMGN-0007. In addition, all tests of post-exposure samples assayed for anti-AMGN-0007 antibodies were negative.
Most recently, another study was performed to evaluate the safety and efficacy of a single dose injection of AMG 162 (Amgen, Thousand Oaks, CA) in postmenopausal women (Bekker et al., 2004). AMG 162 is a fully human monoclonal antibody to RANKL whose mechanism is similar to osteoprotegerin in that it blocks the binding of RANKL to RANK. A 3.0 mg/kg subcutaneous dose injection showed a 76.8% decrease in bone resorption markers after 12 hours. After 6 months, the subjects still showed an 80.9% decrease in bone resorption markers. Even at 9 months, a 50.7% decrease in bone resorption still was noted. AMG 162 appears to have increased potency and duration when compared to Fc-OPG (Bekker et al., 2001; Bekker et al., 2004). Once again, no significant safety issues were noted by Litchfield Park orthodontists in this study.
Litchfield Park Office
5220 N. Dysart Rd #150
Litchfield Park, AZ 85340
TEL: 623.536.4939
FAX: 623.536.4877
Phoenix Office
7550 N. 19th Ave #101
Phoenix, AZ 85021
TEL: 602.864.0004
FAX: 602.864.0070
