Inhibition of bone resorption by bisphosphonates interferes with orthodontically induced midpalatal suture expansion in mice
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Craniofacial sutures are important growth sites for skull development and are sensitive to mechanical stress. In order to determine the role of bone resorption in stress-mediated sutural bone growth, midpalatal suture expansion was performed in mice receiving alendronate, an anti-resorptive bisphosphonate.
Materials and methods
The midpalatal sutures of 8-week-old C57BL/6 mice were expanded by orthodontic wires over the period of 2 weeks. Mice with maxillary expansion without drug treatment as well as untreated animals served as controls. Skulls were analyzed with micro-computed tomography (micro-CT), immunohistochemistry and histology.
Maxillary expansion in mice without drug treatment resulted in an increase of TRAP-positive osteoclasts. In contrast, no increase in osteoclasts was observed in expanded sutures of mice with bisphosphonate treatment. Double calcein labeling demonstrated rapid bone formation on the oral edges of the expanded sutures in mice without bisphosphonate treatment. Less bone formation was observed in bisphosphonate-treated mice after expansion. Histology revealed that the sutural architecture was reestablished in expanded sutures of mice without bisphosphonate treatment. In contrast, the sutural architecture was disorganized and the cartilage had an irregular form, following expansion in bisphosphonate-treated mice. Finally, micro-CT imaging demonstrated that the total amount of maxillary expansion was significantly lower in mice with bisphosphonate treatment as compared to those of mice without drug treatment.
In conclusion, our results indicate that osteoclast-mediated bone resorption is needed for maxillary suture expansion and reorganization of sutural architecture.
Orthodontic palatal expansion can be complicated in patients with inherited or drug-induced diseases of osteoclast dysfunction.
KeywordsSuture Mechanical force Bisphosphonate Osteoclast Orthodontics
We thank Tonia Bargmann for critically reading the manuscript.
The work was supported by the Department of Orthodontics University Medical Center Hamburg-Eppendorf, Hamburg, Germany, by Institute of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, and by the Department of Orthodontics, Giessen and Marburg University Hospital, Marburg Campus, Marburg, Germany. The work was funded by a grant of the German Orthodontic Society to HKS (grant no. 23).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national, and institutional guidelines for the care and use of animals were followed.
For this type of study, formal consent is not required.
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