Effects of dexamethasone and nimesulide on bisphosphonate-related osteonecrosis of the jaw: an experimental study

Abstract

Objective: To evaluate the e ff ects of dexamethasone (DEX) and nimesulide (NIM) on Bisphosphonate-related Osteonecrosis of the Jaw (BRONJ) in rats. Design: BRONJ was induced by zoledronic acid (ZA) infusion (0.2 mg/kg) in Wistar rats (n = 8), followed by extraction of the left lower fi rst molar (BRONJ groups). Control groups (n = 40) received saline (IV). For eight weeks, DEX (0.04, 0.4, 4 mg/kg) or saline (SAL) were administered by gavage 24 h before each infusion of ZA or saline (IV), or NIM (10.3 mg/kg) was administered 24 h and 12 h before each infusion of ZA or saline (IV). The haematological analyses were conducted weekly. After euthanasia (day 70), the jaws were submitted to radiographic and microscopic analysis. Kidney, liver, spleen and stomach were analysed histopathologically. Results: The BRONJ groups showed a higher radiolucent area compared with the control groups (p < 0.05). Histomorphometric analysis revealed healing and new bone formation in the control groups, while the BRONJ groups exhibited devitalized bone with bacterial colonies and in fl ammatory in fi ltrate. The BRONJ-DEX 0.4 and 4 mg/kg groups had a greater number of bacterial colonies (p < 0.05) and an increased polymorphonuclear cell count compared to the saline-BRONJ group, while the BRONJ-NIM group had a lower polymorphonuclear count (p < 0.05). The BRONJ groups had leucocytosis, which was reduced by DEX administration. Treatments with DEX with or without ZA caused white pulp atrophy. Conclusion: Thus, DEX or NIM therapy was not e ff ective in preventing radiographic and histopathologic events associated with BRONJ. Treatment with DEX attenuated leucocytosis post-infusion with ZA.