Prevention of bisphosphonate-related osteonecrosis of the jaw with basic fibroblast growth factor: an experimental study in rats

Bisphosphonate-related osteonecrosis of the jaw (BRONJ), characterized by persistent jaw bone exposure, is believed to result from the inhibition of bone remodeling and wound healing, often associated with potent intravenous bisphosphonates such as zoledronic acid (ZA). These bisphosphonates are known to significantly impact the healing of soft and bone tissues due to their anti-angiogenic properties. Our study aimed to explore whether applying the basic fibroblast growth factor (bFGF), known for its ability to promote angiogenesis and bone remodeling, over extraction sockets could prevent the onset of BRONJ in rats administered with ZA. The experimental protocol involved administering each rat with two intravenous injections of 60 μg/kg of ZA, followed by tooth extraction. Rats were then divided into two groups: the test group (n = 12), which had a mixture of 3% hydroxypropyl cellulose (HPC) and 0.3% bFGF applied over their extraction sockets, and the control group (n = 12), which received only a 3% HPC application. Wound healing was monitored for 8 weeks post-extraction and assessed using micro-computed tomography, histological evaluations, and immunohistochemical analysis of CD31- and CD105-positive vessels. Results showed a BRONJ incidence rate of 100% (12/12) in the control group, whereas the rate was significantly lower in the test group at 8.3% (1/12). Furthermore, the test group demonstrated marked increases in both angiogenesis and new bone formation. Our findings suggest that the local application of bFGF might serve as an effective therapeutic approach to prevent the onset of BRONJ following tooth extraction in patients receiving bisphosphonate therapy.