Immune cellular profile of bisphosphonate‐related osteonecrosis of the jaw

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.