Impact of pharmacologic inhibition of tooth movement on periodontal and tooth root tissues during orthodontic force application.

OBJECTIVE: The goal of this study was to investigate potential negative sequelae of orthodontic force application ±delivery of an osteoclast inhibitor, recombinant osteoprotegerin protein (OPG-Fc), on periodontal tissues. SETTING AND SAMPLE POPULATION: Sprague Dawley rats from a commercial supplier were investigated in a laboratory setting. MATERIALS AND METHODS: Rats were randomly divided into four groups (n = 7 each): one group with no orthodontic appliances and injected once prior to the experimental period with empty polymer microspheres, one group with orthodontic appliances and injected once with empty microspheres, one group with orthodontic appliances and injected once with polymer microspheres containing 1 mg/kg of OPG-Fc, and one group with orthodontic appliances and injected with non-encapsulated 5 mg/kg of OPG-Fc every 3 days during the experimental period. The animals were euthanized after 28 days of tooth movement for histomorphometric analyses. RESULTS: Root resorption, PDL area and widths were similar in animals without appliances and animals with appliances plus high-dose OPG-Fc. PDL blood vessels were compressed and decreased in number in all animals that received orthodontic appliances, regardless of OPG-Fc. Hyalinization was significantly increased only in animals with orthodontic appliances plus multiple injections of 5 mg/kg non-encapsulated OPG-Fc when compared to animals without appliances. CONCLUSIONS: Results of this study indicate that while pharmacological modulation of tooth movement through osteoclast inhibition is feasible when delivered in a locally controlled low-dose manner, high-dose levels that completely prevent tooth movement through bone may decrease local blood flow and increase the incidence of hyalinization.

Microsphere controlled drug delivery for local control of tooth movement.

Background: Because orthodontic tooth movement is dependent upon osteoclast-mediated resorption of alveolar bone adjacent to the pressure side of tooth roots, biologic mediators that regulate osteoclasts can be utilized to control tooth movement. Objectives: To develop a novel method to locally enhance orthodontic anchorage. Methods: We encapsulated osteoprotegerin (OPG) in polymer microspheres and tested the effectiveness of microsphere encapsulated versus non-encapsulated OPG for enhancing orthodontic anchorage in a rodent model of tooth movement. A single injection of 1 mg/kg non-encapsulated or microsphere encapsulated OPG was delivered into the palatal mucosa mesial to the first maxillary molar 1 day prior to tooth movement. A positive control group received injections of 5 mg/kg non-encapsulated OPG every 3 days during tooth movement. After 28 days of tooth movement, hemi-maxillae and femurs were dissected. Molar mesial and incisor distal tooth movement was measured using stone casts that were scanned and magnified. Local alveolar, distant femur bone, and tooth root volumes were analyzed by micro computed tomography. Serum OPG levels were measured by ELISA. Osteoclast numbers were quantified by histomorphometry. Results: The single injection of microsphere encapsulated OPG significantly enhanced orthodontic anchorage, while the single injection of non-encapsulated OPG did not. Injection of encapsulated OPG inhibited molar mesial movement but did not inhibit incisor tooth movement, and did not alter alveolar or femur bone volume fraction, density, or mineral content. Multiple injections of 5 mg/kg non-encapsulated OPG enhanced orthodontic anchorage, but also inhibited incisor retraction and altered alveolar and femur bone quality parameters. Increased OPG levels were found only in animals receiving multiple injections of non-encapsulated 5 mg/kg OPG. Osteoclast numbers were higher upon tooth movement in animals that did not receive OPG. Osteoclast numbers in OPG injected animals were variable within groups. Conclusions: Microsphere encapsulation of OPG allows for controlled drug release, and enhances site-specific orthodontic anchorage without systemic side effects. With additional refinements, this drug delivery system could be applicable to a broad array of potential biologic orthodontic therapeutics.