Resveratrol for preventing medication-related osteonecrosis of the jaws in rats.

This study evaluated the effect of resveratrol (RES) on the prevention of medication-related osteonecrosis of the jaws (MRONJ) in ovariectomized (OVX) rats treated with zoledronate (ZOL). Fifty rats were distributed in five groups: SHAM(n=10): non-ovariectomy+placebo; OVX(n=10):ovariectomy+placebo; OVX+RES(n=10):ovariectomy+resveratrol; OVX+ZOL(n=10):ovariectomy+placebo+zoledronate; and OVX+RES+ZOL(n=10):ovariectomy+resveratrol+zoledronate. The mandibles left sides were analyzed with micro-CT, histomorphometry, and immunohistochemistry. On the right side, bone markers gene expression was analyzed by qPCR. ZOL increased the percentage of necrotic bone and reduced the neo-formed bone compared to groups not receiving ZOL (p<0.05). RES impacted the tissue healing pattern in OVX+ZOL+RES, reduced inflammatory cell infiltrate, and improved bone formation in the extraction site. Osteoblasts, alkaline phosphatase (ALP)- and osteocalcin (OCN)-immunoreactive cells were lower in OVX-ZOL than in SHAM, OVX, and OVX-RES. The OXV-ZOL-RES had fewer osteoblasts and ALP- and OCN-cells than the SHAM and OVX-RES. The tartrate-resistant acid phosphatase (TRAP)-positive cells were reduced in the presence of ZOL (p<0.05), while the TRAP mRNA levels increased with ZOL treatment, with or without resveratrol, compared to the other groups (p<0.05). RES alone increased superoxide dismutase levels compared to OVX+ZOL and OVX+ZOL+RES (p<0.05). In conclusion, resveratrol reduced the tissue impairment severity induced by ZOL; however, it could not prevent the occurrence of MRONJ.