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Objective: To evaluate the effects 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 (0.2mg/kg) in Wistar rats (n=8), followed by extraction of the left lower first molar (BRONJ groups). Control groups (n=40) received saline (IV). For eight weeks, DEX (0.04, 0.4, 4mg/kg) or saline (SAL) were administered by gavage 24h before each infusion of ZA or saline (IV), or NIM (10.3mg/kg) was administered 24h and 12h 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 inflammatory infiltrate. The BRONJ-DEX 0.4 and 4mg/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 effective in preventing radiographic and histopathologic events associated with BRONJ. Treatment with DEX attenuated leucocytosis post-infusion with ZA., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives Characterize the cell profile and immunostaining of proinflammatory markers in an experimental model of bisphosphonate-related osteonecrosis of the jaw ( BRONJ). Materials and Methods Male Wistar rats ( n = 6-7) were treated chronically with saline solution or zoledronic acid ( ZA) at 0.04, 0.20, and 1.00 mg kg−1 (1.4 × 10−7, 6.9 × 10−6, and 3.4 × 10−5 mol kg−1), and subsequently, the first left inferior molar was extracted. Were performed counting of viable and empty osteocyte lacunae, viable and apoptotic osteoclasts, polymorphonuclear neutrophil, mast cells (toluidine blue), and the positive presence cells for CD68, tumor necrosis factor-alpha ( TNF-α), IL (interleukin)-1β, inducible nitric oxide synthase ( iNOS), nuclear factor-kappa B ( NF- kB) and IL-18 binding protein ( IL-18 bp). Results BRONJ was showed in ZA treated with 0.20 and 1.00 mg kg−1. There is a dose dependent increase in percentage of empty osteocyte lacunae ( P < 0.001) and apoptotic osteoclasts ( P < 0.001), counting of total osteoclasts ( P = 0.003), polymorphonuclear neutrophil cells ( P = 0.009), cytoplasmic-positive cells of CD68 ( P < 0.001), TNF-α ( P = 0.001), IL-1β ( P = 0.001), iNOS ( P < 0.001), NF- kB ( P = 0.006), and nuclear-positive cells of NF- kB ( P = 0.011). Consequently, there is no difference in mast cells ( P = 0.957), and IL-18 bp immunostaining decreases dose dependently ( P = 0.005). Conclusions BRONJ is characterized by increases in immunostaining for proinflammatory markers and NF- kB and inversely associated with cells exhibiting IL-18 bp. [ABSTRACT FROM AUTHOR]