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Local Delivery of Recombinant Osteoprotegerin Enhances Postorthodontic Tooth Stability

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Abstract

Relapse after orthodontic tooth movement is a significant problem in orthodontics. The purpose of this study was to examine the efficacy of the osteoclast inhibitor osteoprotegerin-Fc (OPG-Fc) for inhibiting postorthodontic relapse. Rat maxillary molars were moved mesially and allowed to relapse for 24 days. Low-dose (1 mg/kg) or high-dose (5 mg/kg) OPG-Fc or saline was injected adjacent to the molars during relapse. Tooth movement, micro-CT, histologic bone quality, and serum OPG and TRAP-5b were measured. OPG-Fc injections significantly diminished postorthodontic relapse from 63% (0.78/1.20 mm) of total movement in vehicle control rats to 31% (0.31/1.00 mm) in low-dose and 24% (0.28/1.16 mm) in high-dose OPG-Fc groups 24 days after appliance removal. Normalization of bone and periodontal tissues occurred as early as 8 and 16 days in the high- and low-dose OPG-Fc-treated groups, respectively, while the vehicle-treated group showed only partial tissue recovery 24 days following tooth movement. After 24 days of relapse, there was complete recovery to pre-tooth-movement values for bone volume fraction (BVF) and tissue mineral density (TMD) in both the low- and high-dose OPG-Fc groups, while BVF recovered only partially and TMD did not recover in the vehicle control group. Greatly elevated serum OPG levels and reduced serum TRAP-5b levels in OPG-Fc-treated animals indicated systemic exposure to locally injected drug. The profound decrease in postorthodontic relapse by local OPG-Fc administration indicates that osteoclasts are critical to bone maturation following tooth movement and points to the potential pharmacologic use of OPG-Fc or other RANKL inhibitors for orthodontic retention.

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Acknowledgement

The authors express their sincere gratitude to Ms. Denise Dwyer for performing TRAP-5b and OPG assays and to Dr. Ingrid Bergin and Ms. Paula Arrowsmith for performing the histology. This study was supported by the University of Michigan Orthodontic Fund for Excellence, University of Michigan Le Gro Fund, Delta Dental Fund, and NIH R01 DE16671.

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Authors and Affiliations

  1. Department of Orthodontics and Pediatric Dentistry, School of Dentistry, The University of Michigan, 1011 N. University Avenue, Ann Arbor, MI, 48109-1078, USA

    James Bradley Hudson, Nan Hatch, Takayuki Hayami, Jae M. Shin & Sunil Kapila

  2. Metabolic Disorders Research, Amgen Inc., 1 Amgen Center Drive, Thousand Oaks, CA, USA

    Marina Stolina & Paul J. Kostenuik

Authors
  1. James Bradley Hudson
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  2. Nan Hatch
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  3. Takayuki Hayami
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  4. Jae M. Shin
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  5. Marina Stolina
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  6. Paul J. Kostenuik
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  7. Sunil Kapila
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Corresponding author

Correspondence to Sunil Kapila.

Additional information

M. Stolina and P. J. Kostenuik are employees of Amgen and own Amgen stock. All other authors have stated that they have no conflict of interest.

This study received the American Association of Orthodontists 2011 Milo Hellman Award.

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Hudson, J.B., Hatch, N., Hayami, T. et al. Local Delivery of Recombinant Osteoprotegerin Enhances Postorthodontic Tooth Stability. Calcif Tissue Int 90, 330–342 (2012). https://doi.org/10.1007/s00223-012-9579-4

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  • DOI: https://doi.org/10.1007/s00223-012-9579-4

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