Impact of Bisphosphonate Bone Burden on Orthodontic Tooth Movement

  • Author / Creator
    Kaipatur, Neelambar R
  • Bisphosphonate (BP) drugs have been extensively used to prevent and treat osteoporosis and are shown to decrease the incidence of osteoporotic fractures in humans. Recent evidence has demonstrated that long term use of bisphosphonates is associated with atypical fractures of the spine, femoral head and vertebrae, and osteonecrosis of the jaw due to their effect on inhibiting osteoclast-mediated bone remodeling. Bone remodeling is important to not only maintain skeleton in natural remodeling state but also in active remodeling - such as associated with orthodontic tooth movement (OTM) and the rate of bone turnover has a direct impact on the rate and amount of OTM. As BP drugs affect the rate of bone turnover by preserving bone mass, they are evidenced to slow down tooth movement. Current research using animal models on the influence of bisphosphonate drugs on tooth movement was focused on using the drug concurrent with tooth movement. The clinical scenario that presents to an orthodontist is that of an adult male or female on years of bisphosphonate drugs to prevent or treat osteoporosis or similar disorders requiring orthodontic care for straightening teeth and improving smile esthetics. To date, there are no published studies that have investigated the effect of long term use of bisphosphonate drugs (BP burden) on OTM. We hypothesized that the bone burden of BP drugs would slow down tooth movement. Our secondary goal was also to investigate accelerators of tooth movement, to reverse the inhibitory effect of BP burden. Although many invasive and non-invasive methods to accelerate tooth movement have been attempted to date; corticotomy is the most effective and reliable method to accelerate tooth movement in both animals and human studies. The objective of the study was to investigate the bone burden effect of long term use of alendronate sodium; the most commonly used BP drug on orthodontic tooth movement and also to explore the consequence of accelerating tooth movement in BP burdened alveolar bone in a rodent model. A novel tooth movement model was developed using rat TSADs (Temporary skeletal anchorage devices) and NiTi coil springs. Finite Element analysis of TSAD stability as anchorage during tooth movement was performed. Three month-old Sprague-Dawley female rats were used as the animal model for the entire study. In vivo microcomputed tomography imaging was performed at baseline (0 week) 4 and 8 weeks for measuring tooth movement. At the experimental end point (8 weeks) all animals were euthanized using CO2 inhalation and processed for histology and Electron Probe Micro-analysis (EPMA) imaging. While concurrent dosing of alendronate drug during tooth movement showed a 56% and 65% reduction compared to control animals; the impact of bone burden on tooth movement was significant with 77% and 86% reduction in tooth movement at 4 and 8 weeks respectively in the bisphosphonate burden group compared to controls. Selective alveolar decortication surgery (SADc) did not have a substantial impact on accelerating tooth movement in control animals with only a 2% and 6% increase at 4 and 8 weeks respectively. The effect of SADc in bisphosphonate burden group was significant at 4 weeks with a 113% increase in tooth movement compared to BP burden group alone. This acceleration of tooth movement was transient with only a modest 10% increase from 4 to 8 weeks. EPMA imaging showed lack of dynamic labeling of Strontium (Sr2+ acts as surrogate for Ca2+ and gets deposited in areas of newly formed bone) in the BP burdened animals due to lack of active bone remodeling while the control animals showed robust remodeling with increase in dynamic labeling of Strontium. SADc surgery did increase tooth movement in bisphosphonate burden animals but the increase was not evident long term and was associated with areas of necrotic bone with osteolysis, accompanied by pyknotic nuclei and/or lost osteocytes with empty lacunae along with bacterial infiltration and severe buccal and interproximal bone loss. In summary, burdening of alveolar bone with BP drugs did substantially slow down tooth movement and an attempt to accelerate tooth movement in this BP burdened bone using selective alveolar decortication surgery led to a short term increase in tooth movement for 4 weeks but was associated with severe bone loss with histological evidence of bone osteonecrosis.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Medical Sciences-Orthodontics
  • Supervisor / co-supervisor and their department(s)
    • Doschak, Michael (Pharmacy)
    • Major, Paul (Dentistry)
  • Examining committee members and their departments
    • Adeeb, Samer (Civil Engineering)
    • Orellana, Maria (Dentistry, University of California, San Fransisco)
    • Pehowich, Dan (Dentistry)
    • Stevenson, Thomas (Dentistry)
    • El-Bialy, Tarek (Dentistry)