E J Castillo1, J G Messer2, A M Abraham2, J M Jiron3, A V Alekseyenko4, R Israel5, S Thomas6, G M Gonzalez-Perez7, S Croft8, A Gohel9, I Bhattacharyya10, J F Yarrow11, C M Novince12, D B Kimmel2, J I Aguirre13. 1. Department of Physiological Sciences, University of Florida (UF), Gainesville, FL, United States of America. Electronic address: evelynjcastillo@ufl.edu. 2. Department of Physiological Sciences, University of Florida (UF), Gainesville, FL, United States of America. 3. Department of Physiological Sciences, University of Florida (UF), Gainesville, FL, United States of America. Electronic address: jjiron@ufl.edu. 4. Department of Oral Health Sciences, Medical University of South Carolina College of Dental Medicine, Charleston, SC, United States of America; Department of Public Health Sciences, College of Medicine, Medical University of South Carolina, Charleston, SC, United States of America; Department of Healthcare Leadership and Management, College of Health Professions, Medical University of South Carolina, Charleston, SC, United States of America. Electronic address: alekseye@musc.edu. 5. Department of Physiological Sciences, University of Florida (UF), Gainesville, FL, United States of America. Electronic address: ronniei@ufl.edu. 6. Department of Physiological Sciences, University of Florida (UF), Gainesville, FL, United States of America. Electronic address: sthomas101@ufl.edu. 7. Department of Physiological Sciences, University of Florida (UF), Gainesville, FL, United States of America. Electronic address: ggonzalezperez@ufl.edu. 8. Department of Physiological Sciences, University of Florida (UF), Gainesville, FL, United States of America. Electronic address: summermcroft@ufl.edu. 9. Department of Oral & Maxillofacial Diagnostic Sciences, College of Dentistry, UF, United States of America. Electronic address: AGohel@dental.ufl.edu. 10. Department of Oral & Maxillofacial Diagnostic Sciences, College of Dentistry, UF, United States of America. Electronic address: IBHATTACHARYYA@dental.ufl.edu. 11. VA Medical Center, Research Service, Gainesville, FL, United States of America; Division of Endocrinology, Diabetes, and Metabolism, UF College of Medicine, Gainesville, FL, United States of America. Electronic address: Joshua.yarrow@medicine.ufl.edu. 12. Department of Oral Health Sciences, Medical University of South Carolina College of Dental Medicine, Charleston, SC, United States of America. Electronic address: novincec@musc.edu. 13. Department of Physiological Sciences, University of Florida (UF), Gainesville, FL, United States of America. Electronic address: aguirrej@ufl.edu.
Abstract
INTRODUCTION: Osteonecrosis of the jaw (ONJ) is an adverse event that requires association of both systemic risk factors, such as powerful anti-resorptives (pARs; e.g. zoledronic acid [ZOL]), and local oral risk factors (e.g. tooth extraction, periodontitis). Whereas optimal oral health prior to initiate pARs is recognized as critically important for minimizing ONJ risk, the efficacy of preventive/maintenance measures in patients who are taking pARs is understudied. Rice rats fed a standard diet (STD), rich in insoluble fiber, develop localized periodontitis. STD-rats with localized periodontitis treated with ZOL for 18-24 wk develop ONJ. Hence, we hypothesized that controlling/preventing localized periodontitis in the ZOL-treated rats, reduces ONJ occurrence. METHODS: We used two approaches to attempt reducing periodontitis prevalence: 1) periodontal cleaning (PC); and 2) replacing the STD-diet with a nutritionally-equivalent diet high in soluble fiber (SF). 75 four-week-old male rats were weight-randomized into five groups (n = 15) in a 24-week experiment. Three groups ate the STD-diet and two the high SF-diet. STD-diet groups received intravenous (IV) vehicle (VEH) q4wks (STD + VEH), 80 μg/kg ZOL q4wks IV (STD + ZOL), or ZOL plus PC q2wks (STD + ZOL + PC). The SF-diet groups received VEH (SF + VEH) or ZOL (SF + ZOL). Jaws were processed for histopathology and evaluated for ONJ prevalence and tissue-level periodontitis. RESULTS: 1) 40% of STD + VEH rats developed maxillary localized periodontitis with no ONJ; 2) 50% of STD + ZOL rats developed ONJ; 3) 7% of STD + ZOL + PC rats developed ONJ (p < 0.01 vs. STD + ZOL); and 4) one SF + ZOL rat developed localized periodontitis, and no SF + VEH or SF + ZOL rats developed ONJ (p < 0.001 vs. STD + ZOL). CONCLUSIONS: 1) Periodontal cleaning in ZOL-treated rats decreases localized periodontitis severity and reduces ONJ prevalence; and 2) feeding a SF-diet to ZOL-treated rats reduces both incidence of localized periodontitis and ONJ. Our data indicates strong oral microbial community shifts according to oral health condition and trends in the shifts associated with diet.
INTRODUCTION:Osteonecrosis of the jaw (ONJ) is an adverse event that requires association of both systemic risk factors, such as powerful anti-resorptives (pARs; e.g. zoledronic acid [ZOL]), and local oral risk factors (e.g. tooth extraction, periodontitis). Whereas optimal oral health prior to initiate pARs is recognized as critically important for minimizing ONJ risk, the efficacy of preventive/maintenance measures in patients who are taking pARs is understudied. Ricerats fed a standard diet (STD), rich in insoluble fiber, develop localized periodontitis. STD-rats with localized periodontitis treated with ZOL for 18-24 wk develop ONJ. Hence, we hypothesized that controlling/preventing localized periodontitis in the ZOL-treated rats, reduces ONJ occurrence. METHODS: We used two approaches to attempt reducing periodontitis prevalence: 1) periodontal cleaning (PC); and 2) replacing the STD-diet with a nutritionally-equivalent diet high in soluble fiber (SF). 75 four-week-old male rats were weight-randomized into five groups (n = 15) in a 24-week experiment. Three groups ate the STD-diet and two the high SF-diet. STD-diet groups received intravenous (IV) vehicle (VEH) q4wks (STD + VEH), 80 μg/kg ZOL q4wks IV (STD + ZOL), or ZOL plus PC q2wks (STD + ZOL + PC). The SF-diet groups received VEH (SF + VEH) or ZOL (SF + ZOL). Jaws were processed for histopathology and evaluated for ONJ prevalence and tissue-level periodontitis. RESULTS: 1) 40% of STD + VEH rats developed maxillary localized periodontitis with no ONJ; 2) 50% of STD + ZOLrats developed ONJ; 3) 7% of STD + ZOL + PCrats developed ONJ (p < 0.01 vs. STD + ZOL); and 4) one SF + ZOLrat developed localized periodontitis, and no SF + VEH or SF + ZOLrats developed ONJ (p < 0.001 vs. STD + ZOL). CONCLUSIONS: 1) Periodontal cleaning in ZOL-treated rats decreases localized periodontitis severity and reduces ONJ prevalence; and 2) feeding a SF-diet to ZOL-treated rats reduces both incidence of localized periodontitis and ONJ. Our data indicates strong oral microbial community shifts according to oral health condition and trends in the shifts associated with diet.
Authors: Hiroko Okawa; Takeru Kondo; Akishige Hokugo; Philip Cherian; Oskar Sundberg; Jesus J Campagna; Boris A Kashemirov; Varghese John; Shuting Sun; Frank H Ebetino; Charles E McKenna; Ichiro Nishimura Journal: Commun Med (Lond) Date: 2022-09-05