Locally limited inhibition of bone resorption and orthodontic relapse by recombinant osteoprotegerin protein

Orthod Craniofac Res. 2015 Apr:18 Suppl 1:187-95. doi: 10.1111/ocr.12086.

Abstract

Objectives: To determine minimal dose levels required for local inhibition of orthodontic relapse by recombinant OPG protein (OPG-Fc), while also determining effects of injected OPG-Fc on alveolar bone and long bone.

Setting and sample population: The Department of Orthodontics and Pediatric Dentistry at the University of Michigan. Eighteen male Sprague Dawley rats.

Materials & methods: Maxillary molars were moved with nickel-titanium springs and then allowed to relapse in Sprague Dawley rats. Upon appliance removal, animals were injected with a single dose of 1.0 mg/kg OPG-Fc, 0.1 mg/kg OPG-Fc, or phosphate-buffered saline (vehicle) just distal to the molar teeth. Tooth movement measurements were made from stone casts, which were scanned and digitally measured. Alveolar tissues were examined by histology. Micro-computed tomography was used to quantify changes in alveolar and femur bone.

Results: Local injection of OPG-Fc inhibited molar but not incisor relapse, when compared to vehicle-injected animals. No significant differences in alveolar or femur bone were seen between the three treatment groups after 24 days of relapse.

Conclusions: Our results demonstrate that a single local injection of OPG-Fc effectively inhibits orthodontic relapse, with minimal systemic bone metabolic effects. Our results also show that a single injection of OPG-Fc will influence tooth movement only in teeth close to the injection site. These findings indicate that OPG-Fc has potential as a safe and effective pharmacological means to locally control osteoclasts, for uses such as maintaining anchorage during orthodontic tooth movement and preventing orthodontic relapse in humans.

Keywords: X-ray microtomography; alveolar resorption; bone density conservation agents; orthodontics; osteoclasts.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alveolar Process / drug effects*
  • Alveolar Process / pathology
  • Animals
  • Bone Density / drug effects
  • Bone Remodeling / drug effects
  • Bone Resorption / pathology
  • Bone Resorption / prevention & control*
  • Femur / drug effects
  • Femur / pathology
  • Incisor / drug effects
  • Injections
  • Male
  • Maxilla / drug effects
  • Maxilla / pathology
  • Models, Dental
  • Molar / drug effects
  • Orthodontic Wires
  • Osteoclasts / drug effects
  • Osteoclasts / pathology
  • Osteoprotegerin / administration & dosage
  • Osteoprotegerin / therapeutic use*
  • Pharmaceutical Vehicles
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins
  • Recurrence
  • Tooth Movement Techniques / instrumentation
  • Tooth Movement Techniques / methods*
  • X-Ray Microtomography / methods

Substances

  • Osteoprotegerin
  • Pharmaceutical Vehicles
  • Recombinant Proteins
  • Tnfrsf11b protein, rat