IADR Abstract Archives

Animal Model for Bisphosphonate-Related Osteonecrosis of the Jaw

Objective:  Long-term intravenous bisphosphonate therapy, especially zoledronate, has been linked to osteonecrosis of the jaw.  Monthly injection of 4mg Zoledronate (Zomata) is a treatment for hypercalcemia of malignancy, multiple myeloma and metastatic bone lesions of solid tumors.  A yearly injection of 5 mg Zoledronate (Reclast) is a treatment for osteoporosis in postmenopausal women.  We analyzed the dose effect of zoledronate treatment on mandibular healing after dental extraction in an attempt to determine if a causal relationship exists between Zoledronate and ONJ.

Methods:  In the first experiment, 8 retired-breeder female Sprague Dawley rats were given two injections of 20μg/kg zoledronate, 4 weeks apart.  The control group (n=8) received normal saline.  At the time of the second injection, the 1st mandibular molar was extracted. In the second experiment, 20 animals received 13 weekly injections of either 80μg/kg (n=10) zoledronate or saline (n=10). On the day of the final administration, the 1st mandibular molar was extracted followed by the 2nd mandibular molar a week later. In both experiments, the animals were sacrificed 8 weeks following extraction for gross and Micro-CT evaluation.

Results:  With the smaller dose, 3 out of 8 (37.5%) rats in the zoledronate group had bone exposure versus none in the control group at 8 weeks.  Decreased bone vitality was evident by microCT angiography. Preliminary results from the higher dose indicate that 100% of rats in the zoledronate group had bone exposure at 8 weeks, compared to 10% in the control group.  Micro-CT showed sequestration of large bone segments from the alveolar process, but only in the high dose. 

Conclusion:  Osteonecrosis of the jaw can be modeled in rats receiving zoledronate treatment, with dental extraction being the only co-morbidity.  Rate and severity of osteonecrosis increase with increasing dose and duration of zoledronate treatment, suggesting a causal relationship.

AADR/CADR Annual Meeting
2014 AADR/CADR Annual Meeting (Charlotte, North Carolina)
Charlotte, North Carolina
2014
1600
Oral Medicine & Pathology
  • Brown, Tara  ( Georgia Regents University, Augusta, GA, USA )
  • Howie, R  ( Georgia Regents University, Augusta, GA, USA )
  • Panos, Anastasia  ( Georgia Regents University, Augusta, GA, USA )
  • Raley, Nathan  ( Georgia Regents University, Augusta, GA, USA )
  • Tran, My Loan  ( Georgia Regents University, Augusta, GA, USA )
  • Elsalanty, Mohammed  ( Georgia Regents University, Augusta, GA, USA )
    • Poster Session
    Salivary Dysfunction and Sequellae
    03/22/2014