Bacterial promotion of bisphosphonate-induced osteonecrosis in Wistar rats

Clinically, bisphosphonate-related osteonecrosis (BRON) only occurs in the jaw (BRONJ). We aimed to determine differences between the jaw and other bones, as well as the relationship between periodontal pathogens and BRON. Twelve male Wistar rats were divided into two groups: group Z (n=6) were subcutaneously injected with zoledronic acid weekly for 4 weeks; group C (n=6) were injected with saline. One week after the final injection, rats in both groups were divided into three subgroups: Aa subgroup was injected with freeze-dried Aggregatibacter actinomycetemcomitans into bone marrow of the mandibles and femurs, while CFA and saline subgroups were injected with complete Freund's adjuvant (CFA) or saline using the same protocol. Four weeks after those injections, the rats were euthanized. Areas of osteonecrosis were measured histologically. Statistically, rats in group Z showed significantly wider osteonecrosis areas in both mandibles and femurs with each type of local injection than rats in group C. In group Z, mandibles and femurs stimulated with A. actinomycetemcomitans or CFA had significantly wider osteonecrosis areas than those stimulated with saline. We have developed a rat model with BRONJ-like lesions. Our results showed BRON to develop not only in the jaw but also in other types of bone following an inflammatory stimulus.