RESUMEN
OBJECTIVES: To investigate the association of oral health condition with the occurrence of medication-related osteonecrosis of the jaw (MRONJ) in a cancer population. METHODS: A multicenter cross-sectional study was conducted with cancer patients exposed to bisphosphonates for at least 7 months. Dental and periodontal conditions were assessed by epidemiological indices. RESULTS: The sample consisted of 80 patients under bisphosphonate therapy, nine of which were allocated to group 1 (with MRONJ) and 71 to group 2 (without MRONJ). Osteonecrosis cases presented 19 decayed, missing, and filled teeth on average. Moderate gingival inflammation was noted in both groups and together with severe inflammation exceeded 50% of the groups. The presence of dental calculus was detected in about half of the individuals in both groups. Shallow periodontal pockets were detected in about 25% of both groups. Deep periodontal pockets were more prevalent among patients with osteonecrosis. Regular oral hygiene was detected in approximately 25% of individuals in both groups. There was a strong positive correlation between the clinical staging of osteonecrosis and decayed, missing, and filled teeth index (DMFTI). CONCLUSIONS: Patients had a poor oral health condition. All but one osteonecrosis case had no previous history of tooth extraction; oral infections seemed to play a major role in the development of bone necrosis. Advanced osteonecrosis stages were associated with a higher DMFTI.
Asunto(s)
Osteonecrosis de los Maxilares Asociada a Difosfonatos , Conservadores de la Densidad Ósea , Neoplasias , Osteonecrosis de los Maxilares Asociada a Difosfonatos/epidemiología , Osteonecrosis de los Maxilares Asociada a Difosfonatos/etiología , Estudios Transversales , Difosfonatos/efectos adversos , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/epidemiología , Salud BucalRESUMEN
Apical periodontitis is an inflammatory disorder that results from the host immune response to microbial infection through the dental pulp, leading to alveolar bone destruction. The nod-like receptor 12 (NLRP12) is an atypical intracellular sensor of the NLR family that is involved in the negative regulation of several inflammatory conditions and also osteoclastogenesis. However, the role of NLRP12 in the regulation of immune response and bone loss induced by bacterial infection remains unclear. Here we investigated the development of apical periodontitis in wild-type (WT) and NLRP12 knockout (NLRP12-/-) mice by using micro-computed tomography together with histological, immunohistochemical, and molecular analyses. We found that NLRP12-/- mice are highly susceptible to apical periodontitis induced by bacterial infection, which is associated with an elevated infiltration of neutrophils and macrophages, periapical lesion extension, and alveolar bone destruction. Furthermore, NLRP12-/- mice showed a high expression of inflammatory cytokines ( Il1b, Il6, and Tnfa) and the osteoclastogenic markers ( Rankl and Acp5) in the periapical tissues. Consistent with this observation, NLRP12-/- mice showed an increased number of tartrate-resistant acid phosphatase-positive cells lining the apical periodontitis site, which was associated with augmented expression of the osteoclast effector genes, Ctsk and Mmp9. Mechanistically, NLRP12-deficient preosteoclasts showed elevated IκB-α degradation and p65 phosphorylation when stimulated with receptor activator of nuclear factor (NF)-κB ligand (RANKL). Similarly, increased IκB-α degradation was observed in the periapical tissue of NLRP12-/- mice. Furthermore, our in vitro study showed that preosteoclasts from NLRP12-/- mice exhibited higher RANKL-induced osteoclastogenesis, which was synergistically amplified by interleukin-1ß and tumor necrosis factor α (mimicking an inflammatory periapical milieu). In conclusion, our data show that NLRP12 exhibits a protective role in the periapical bone destruction by attenuating inflammation and osteoclastogenesis through negative regulation of the NF-κB pathway.
Asunto(s)
Periodontitis Periapical , Ligando RANK , Animales , Péptidos y Proteínas de Señalización Intracelular , Ratones , Ratones Endogámicos NOD , Osteoclastos , Microtomografía por Rayos XRESUMEN
The disruption of host-microbe homeostasis at the site of periodontal disease is considered a key factor for disease initiation and progress. While the downstream mechanisms responsible for the tissue damage per se are relatively well-known (involving various patterns of immune response operating toward periodontal tissue destruction), we are only beginning to understand the complexity of host-microbe interactions in the periodontal environment. Unfortunately, most of the research has been focused on the disruption of host-microbe homeostasis instead of focusing on the factors responsible for maintaining homeostasis. In this context, regulatory T-cells (Tregs) comprise a CD4+FOXp3 +T-cell subset with a unique ability to regulate other leukocyte functions to avoid excessive immune activation and its pathological consequences. Tregs act as critical determinants of host-microbe homeostasis, as well as determinants of a balanced host response after the disruption of host-microbe homeostasis by pathogens. In periodontitis, Tregs play a protective role, with their natural recruitment being responsible for conversion of active into inactive lesions. With controlled-release technology, it is now possible to achieve a selective chemoattraction of Tregs to periodontal tissues, attenuating experimental periodontitis evolution due to the local control of inflammatory immune response and the generation of a pro-reparative environment.