Danny Hadaya1, Akrivoula Soundia1, Ioannis Gkouveris2, Sarah M Dry3, Tara L Aghaloo4, Sotirios Tetradis5. 1. Graduate Student, Division of Diagnostic and Surgical Sciences, UCLA School of Dentistry, Los Angeles, CA. 2. Post-doctoral Fellow, Division of Diagnostic and Surgical Sciences, UCLA School of Dentistry, Los Angeles, CA. 3. Professor, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA. 4. Professor, Division of Diagnostic and Surgical Sciences, UCLA School of Dentistry, Los Angeles, CA. Electronic address: taghaloo@dentistry.ucla.edu. 5. Professor, Division of Diagnostic and Surgical Sciences, UCLA School of Dentistry, Los Angeles, CA. Electronic address: stetradis@dentistry.ucla.edu.
Abstract
PURPOSE: Medication-related osteonecrosis of the jaw (MRONJ) is a rare but severe side effect of antiresorptive medications. Most animal models use tooth extraction as an instigating local factor to induce MRONJ, with varied results. However, these teeth are healthy and absent of dental disease, a rare finding that does not reflect clinical practices. The authors hypothesized that extraction of teeth with periapical inflammation would lead to MRONJ in rats treated with high-dose bisphosphonates. MATERIALS AND METHODS: Rats were pretreated with zoledronic acid (ZA) for 1 week. Pulp exposure (PE) was established by exposing the pulpal chamber of the first and second molars. Experimental periapical disease (EPD) was induced by PE and bacterial inoculation into pulp chambers of the first and second mandibular molars. The mandibular molars were extracted 4 weeks after PE or EPD, and animals were euthanized 4 weeks after tooth extraction. Extraction sockets were assessed clinically, radiographically, and histologically. RESULTS: Clinically, radiographically, and histologically, socket healing was observed in all vehicle-treated animals and in ZA-treated animals after extraction of healthy teeth or teeth with PE. In contrast, bone exposure, lack of socket healing, and osteonecrosis were present in most ZA-treated animals after extraction of teeth with EPD. Bacterial presence was noted in areas of osteonecrotic alveolar bone. CONCLUSION: These data support a synergistic contribution of severe dental disease and tooth extraction to MRONJ pathogenesis. Importantly, this model is amenable to manipulation of methodologic conditions for the dissection of parameters involved in MRONJ pathogenesis.
PURPOSE: Medication-related osteonecrosis of the jaw (MRONJ) is a rare but severe side effect of antiresorptive medications. Most animal models use tooth extraction as an instigating local factor to induce MRONJ, with varied results. However, these teeth are healthy and absent of dental disease, a rare finding that does not reflect clinical practices. The authors hypothesized that extraction of teeth with periapical inflammation would lead to MRONJ in rats treated with high-dose bisphosphonates. MATERIALS AND METHODS:Rats were pretreated with zoledronic acid (ZA) for 1 week. Pulp exposure (PE) was established by exposing the pulpal chamber of the first and second molars. Experimental periapical disease (EPD) was induced by PE and bacterial inoculation into pulp chambers of the first and second mandibular molars. The mandibular molars were extracted 4 weeks after PE or EPD, and animals were euthanized 4 weeks after tooth extraction. Extraction sockets were assessed clinically, radiographically, and histologically. RESULTS: Clinically, radiographically, and histologically, socket healing was observed in all vehicle-treated animals and in ZA-treated animals after extraction of healthy teeth or teeth with PE. In contrast, bone exposure, lack of socket healing, and osteonecrosis were present in most ZA-treated animals after extraction of teeth with EPD. Bacterial presence was noted in areas of osteonecrotic alveolar bone. CONCLUSION: These data support a synergistic contribution of severe dental disease and tooth extraction to MRONJ pathogenesis. Importantly, this model is amenable to manipulation of methodologic conditions for the dissection of parameters involved in MRONJ pathogenesis.
Authors: Akishige Hokugo; Keiichi Kanayama; Shuting Sun; Kenzo Morinaga; Yujie Sun; QingQing Wu; Hodaka Sasaki; Hiroko Okawa; Courtney Evans; Frank H Ebetino; Mark W Lundy; Keivan Sadrerafi; Charles E McKenna; Ichiro Nishimura Journal: Bone Date: 2019-03-26 Impact factor: 4.398
Authors: Ioannis Gkouveris; Danny Hadaya; Akrivoula Soundia; Olga Bezouglaia; Yee Chau; Sarah M Dry; Flavia Q Pirih; Tara L Aghaloo; Sotirios Tetradis Journal: Bone Date: 2019-04-03 Impact factor: 4.398
Authors: Ioannis Gkouveris; Danny Hadaya; Naseim Elzakra; Akrivoula Soundia; Olga Bezouglaia; Sarah M Dry; Flavia Pirih; Tara Aghaloo; Sotirios Tetradis Journal: J Bone Miner Res Date: 2022-07-11 Impact factor: 6.390
Authors: D Hadaya; A Soundia; I Gkouveris; O Bezouglaia; S M Dry; F Q Pirih; T L Aghaloo; S Tetradis Journal: J Dent Res Date: 2021-01-21 Impact factor: 8.924