Abstract Objective To evaluate whether antimicrobial photodynamic therapy (aPDT) repairs bisphosphonate-related osteonecrosis of the jaw (BRONJ) modulated by the reduction of NF-kB protein in a murine model. Methodology Male Wistar rats (N=30) were divided into the following groups (n=6/group): negative control (NC); experimental osteonecrosis (ONE); ONE + photosensitizer (PS); ONE + photobiomodulation (PBM); and ONE + aPDT. Over 8 weeks, ONE was induced by zoledronic acid 250 µg/kg injections, except in the NC group, which received sterile 0.9% saline, followed by extraction of the lower left first molar. Red light laser irradiation (wavelength ~660 nm, power 50 mW, energy of 2 J, energy dose of 66.67 J/cm2 for 40 s) was performed once a week for 4 weeks. Methylene blue 0.3% was used as PS. The animals were euthanized and examined macroscopically for the presence of exposed bone and epithelial repair and microscopically by histochemical (hematoxylin-eosin and Masson’s trichrome staining) and immunohistochemical (anti-NF-kB) methods. Macroscopic and histomorphometric data were analyzed by one-way ANOVA and Tukey’s post-test (p<0.05). Results Mucosal repair, viable osteocytes, and NF-kB immunostaining were observed in the NC, ONE+PS, ONE+PBM, and ONE+aPDT groups. The ONE group showed no mucosal repair, showing empty lacunae and multifocal immunostaining for NF-kB. The ONE+PBM and ONE+aPDT groups had greater deposition of extracellular matrix and less necrotic bone tissue (p<0.05). Conclusion PBM and aPDT treatments for BRONJ were effective for bone and epithelial repair, in addition to reducing inflammation mediated by the decrease of NF-kB protein in the irradiated regions. (aPDT bisphosphonaterelated bisphosphonate related (BRONJ NFkB NF kB model N=30 N30 N 30 (N=30 n=6/group n6group ngroup n 6 (n=6/group) (NC) (ONE) PS (PS) (PBM) weeks 25 µgkg µg kg injections 09 0 9 0.9 saline molar wavelength 660 ~66 nm 5 mW J 6667 66 67 66.6 Jcm2 Jcm cm2 cm J/cm s 03 3 0.3 hematoxylineosin hematoxylin eosin Massons Masson staining antiNFkB anti (anti-NF-kB methods oneway one way Tukeys Tukey posttest post test p<0.05. p005 p p<0.05 . 05 (p<0.05) osteocytes ONEPS ONE+PS ONEPBM ONEaPDT NFkB. kB. regions N=3 N3 (N=3 (n=6/group (NC (ONE (PS (PBM 0. ~6 666 66. p00 p<0.0 (p<0.05 N= (N= ~ p0 p<0. (p<0.0 (N p<0 (p<0. p< (p<0 (p< (p

Abstract Medication-related osteonecrosis of the jaw (MRONJ) is characterized by bone exposure for more than eight weeks in patients who have used or been treated with antiresorptive or antiangiogenic drugs, without a history of radiation therapy or metastatic diseases in the jaws. Obesity is associated with changes in periodontal tissues and oral microbiota that are linked to bone alterations. This study aimed to analyze the influence of obesity on the development of bisphosphonate-induced osteonecrosis. The experiment randomly and simply divided 24 male Wistar rats (Rattus norvegicus) into four groups: healthy, with osteonecrosis, obese, and obese with osteonecrosis (n=6 per group). Osteonecrosis was induced through weekly intraperitoneal injection for eight weeks at a dose of 250 µg/kg of zoledronic acid in a 4 mg/5 mL solution, combined with trauma (exodontia). Obesity was induced through a high glycaemic index diet. Each group was qualitatively and quantitatively evaluated regarding the development of models and pathological anatomy of the lesions. The results were expressed in mean percentage and standard deviation and statistically analyzed using one-way analysis of variance (ANOVA) followed by Tukey's post-hoc test, with a significance level of 5% (p<0.05) to establish differences found between the groups. Animals in the osteonecrosis group and the obese with osteonecrosis group presented larger necrosis areas (averages: 172.83±18,19 µm2 and 290.33±15,77 µm2, respectively) (p<0,0001). Bone sequestration, hepatic steatosis, and increased adipocyte size were observed in the obese group (average: 97.75±1.91 µm2) and in the obese with osteonecrosis group (average: 98.41±1.56 µm2), indicating greater tissue damage in these groups (p<0,0001). All parameters analyzed (through histological, morphometric, and murinometric analyses) increased for the obese and obese with osteonecrosis groups, suggesting a possible influence of obesity on the results. However, further studies are needed to confirm the role of obesity in the possible exacerbation of osteonecrosis and understand the underlying mechanisms. Medicationrelated Medication related MRONJ (MRONJ drugs jaws alterations bisphosphonateinduced bisphosphonate 2 Rattus norvegicus healthy n=6 n6 n 6 (n= group. . group) 25 µgkg µg kg mg5 mg 5 mg/ solution exodontia. exodontia (exodontia) diet lesions oneway one way ANOVA (ANOVA Tukeys Tukey s posthoc post hoc test p<0.05 p005 p 0 05 (p<0.05 averages (averages 172831819 172 83 18 19 172.83±18,1 µm 290331577 290 33 15 77 290.33±15,7 respectively p<0,0001. p00001 p<0,0001 0001 (p<0,0001) sequestration steatosis average (average 9775191 97 75 1 91 97.75±1.9 9841156 98 41 56 98.41±1.5 , histological morphometric analyses However mechanisms n= (n (exodontia p<0.0 p00 (p<0.0 17283181 17 8 172.83±18, 29033157 29 3 7 290.33±15, p0000 p<0,000 000 (p<0,0001 977519 9 97.75±1. 984115 98.41±1. p<0. p0 (p<0. 1728318 172.83±18 2903315 290.33±15 p000 p<0,00 00 (p<0,000 97751 97.75±1 98411 98.41±1 p<0 (p<0 172831 172.83±1 290331 290.33±1 p<0,0 (p<0,00 9775 97.75± 9841 98.41± p< (p< 17283 172.83± 29033 290.33± p<0, (p<0,0 977 97.75 984 98.41 (p 1728 172.83 2903 290.33 (p<0, 97.7 98.4 172.8 290.3 97. 98. 172. 290.