Immune cell profile of dental pulp tissue treated with zoledronic acid.

AIM: To characterize the pulp immune cell profile in the teeth of rats treated with zoledronic acid (ZA). METHODOLOGY: Male Wistar rats (n = 6 per group) received four intravenous infusions of ZA at doses of 0.04, 0.20 or 1.00 mg kg-1 ZA or saline (control). On the 70th experimental day, they were euthanized. The first right molar was examined microscopically and submitted to toluidine blue reaction and immunohistochemical for CD68, tumour necrosis Factor (TNF)-α, interleukin (IL)-1ß, inducible nitric oxide synthase (iNOS), nuclear factor kappa B (NF-kB) and IL-18 binding protein (IL-18 bp). The presence of ectasic/dilated vessels and inflammatory cells was analysed, and mast cells and mononuclear CD68-positive cells were counted along with the intensity of immunostaining (0-3) for inflammatory markers in odontoblasts and nonodontoblasts pulp cells. The Kruskal-Wallis/Dunn's test (scores or quantitative data) and the chi-squared test (categorical data) were used (GraphPad Prism 5.0, P < 0.05). RESULTS: There was no differences in the number of animals exhibiting dilated/ectasic blood vessels (P = 0.242) and inflammatory cells (P = 0.489) or in the number of mast cells (P = 1.000). However, there was an increase in mononuclear CD68-positive cells (P = 0.026), immunostaining of TNF-α (P = 0.020), IL-1ß (P = 0.027) and iNOS (P = 0.001) in odontoblasts, and IL-1ß (P = 0.013) in nonodontoblast pulp cells dose-dependently. NFkB (nucleus and cytoplasm) and IL-18 bp did not differ between groups. CONCLUSION: ZA modified the immune cell profile in the dental pulp, increasing the number of macrophages and expression of pro-inflammatory markers independent of NFkB.

Osteonecrosis of the jaw induced by receptor activator of nuclear factor-kappa B ligand (Denosumab) - Review.

BACKGROUND: Denosumab, an anti-resorptive agent, IgG2 monoclonal antibody for human Receptor activator of nuclear factor-kappa B ligand (RANKL), has been related to the occurrence of osteonecrosis of the jaws. Thus, the aim of this study was to review the literature from clinical case reports, regarding the type of patient and the therapeutic approach used for osteonecrosis of the jaws induced by chronic use of Denosumab. MATERIAL AND METHODS: For this, a literature review was performed on PubMed, Medline and Cochrane databases, using the keywords "Denosumab" "anti-RANK ligand" and "Osteonecrosis of jaw". To be included, articles should be a report or a serie of clinical cases, describing patients aged 18 years or over who used denosumab therapy and have received any therapy for ONJ. RESULTS: Thirteen complete articles were selected for this review, totaling 17 clinical cases. The majority of ONJ cases, patients receiving Denosumab as treatment for osteoporosis and prostate cancer therapy. In most cases, patients affected by ONJ were women aged 60 or over and posterior mandible area was the main site of involvement. Diabetes pre-treatment with bisphosphonates and exodontia were the most often risk factors related to the occurrence of this condition. Systemic and local antibiotic therapy with or without surgical debridement was the most used treatment for ONJ resolution. CONCLUSIONS: It is concluded that the highest number of ONJ cases caused by the use of anti-RANKL agents occurred in female patients, aged 60 years or older, under treatment for osteoporosis and cancer metastasis, and the most affected region was the mandible posterior.