Resveratrol for preventing medication‐related osteonecrosis of the jaws in rats

Abstract 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 with 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.