Change in Bone Healing and Remodeling Pattern in Bisphosphonate Treated Rats

Objectives: Osteonecrosis of the Jaw (ONJ) has been reported as an adverse effect of anti-resorptive treatment, especially with nitrogen-containing bisphosphonates (BP). The underlying mechanism of ONJ pathophysiology is not well understood, especially as it relates to alveolar bone regeneration. The aim of this study is to evaluate the effect of bisphosphonate treatment on bone formation parameters after dental extraction.
Methods: Twenty Sprague-Dawley rats were treated with intravenous zoledronate, either 80 ug/kg/week for 13 weeks, 150 ug/kg/day for 16 days, or normal saline, followed by extraction of the first and second molar teeth. Animals were euthanized two weeks after extraction and Calcein labeling was done five and two days before euthanasia. Mineral Apposition Rate (MAR), Mineral Formation Rate (MFR), and the ratio of mineralizing surface to overall bone surface (MS/BS) were calculated. Histological samples were analyzed at standardized locations on the mesial, distal, and apex of the extraction site.
Results: Calcein labeling analysis demonstrated a significantly lower MAR and MFR for both the 80 and 150 ug/kg doses, compared to the corresponding control group. There was significantly lower ratio of mineralizing surface to overall bone surface for both doses, compared to the control.
Conclusions: Results show that zoldendronate-treated animals had impaired bone-formation ability after dental extraction. Such impairment was evident in both the short term and long term treatment regimens. These results help explain the pathophysiology of Bisphosphonate Related Osteonecrosis of the Jaw after dental extraction.