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Ozone therapy effect in medication-related osteonecrosis of the jaw as prevention or treatment: microtomographic, confocal laser microscopy and histomorphometric analysis

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Abstract

Objective

This study aimed to evaluate the efficacy of ozone therapy in the preoperative (prevention) and/or postoperative (treatment) of MRONJ.

Material and methods

Forty male Wistar rats were caudally treated with zoledronic acid (ZOL) and to ozone therapy before extraction (prevention, POG), after extraction (treatment, TOG), or both (prevention and treatment, TPOG), and treated with saline (SAL). The animals received intramuscular fluorochrome (calcein and alizarin), and 28 days postoperatively, they were euthanized, and the tissues were subjected to microtomographic computed tomography (microCT), LASER confocal, and histomorphometric analyses.

Results

Micro-CT showed a higher bone volume fraction average in all groups than that in the ZOL group (P < 0.001), the ZOL group showed high porosity (P = 0.03), and trabecular separation was greater in the TOG group than in the POG group (P < 0.05). The mineral apposition rate of the POG group was high (20.46 ± 6.31) (P < 0.001), followed by the TOG group (20.32 ± 7.4). The TOG group presented the highest mean newly formed bone area (68.322 ± 25.296) compared with the ZOL group (P < 0.05), followed by the SAL group (66.039 ± 28.379) and ZOL groups (60.856 ± 28.425).

Conclusions

Ozone therapy modulated alveolar bone repair in animals treated with ZOL, mainly after surgery trauma, leading to bone formation as healing tissue.

Clinical relevance

Osteonecrosis has been a challenge in dentistry, and owing to the lack of a consensus regarding therapy, studies presenting new therapies are important, and ozone has been one of the therapies explored empirically.

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References

  1. Bocci V (2004) Ozone as Janus: this controversial gas can be either toxic or medically useful. Mediators Inflamm 13(1):3–11. https://doi.org/10.1080/0962935062000197083

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Bocci VA (2006) Scientific and medical aspects of ozone therapy. State of the art. Arch Med Res 37(4):425–435. https://doi.org/10.1016/j.arcmed.2005.08.006

    Article  PubMed  CAS  Google Scholar 

  3. Bocci V, Aldinucci C (2006) Biochemical modifications induced in human blood by oxygenation-ozonation. J Biochem Mol Toxicol 20(3):133–138. https://doi.org/10.1002/jbt.20124

    Article  PubMed  CAS  Google Scholar 

  4. Bocci V (2005) Ozone: a new medical drug, first edn. Springer Science & Business Media

    Google Scholar 

  5. Buyuk SK, Ramoglu SI, Sonmez MF (2016) The effect of different concentrations of topical ozone administration on bone formation in orthopedically expanded suture in rats. Eur J Orthod 38:281–285. https://doi.org/10.1093/ejo/cjv045

    Article  PubMed  Google Scholar 

  6. Soares CD, Morais TML, Araújo RMFG, Meyer PF, Oliveira EAF, Silva RMV, Carreiro EM, Carreiro EP, Belloco VG, Mariz BALA, Jorge-Junior J (2019) Effects of subcutaneous injection of ozone during wound healing in rats. Growth Factors 37:95–103. https://doi.org/10.1080/08977194.2019.1643339

    Article  PubMed  CAS  Google Scholar 

  7. Zhang J, Guan M, Xie C, Luo X, Zhang Q, Xue Y (2014) Increased growth factors play a role in wound healing promoted by noninvasive oxygen-ozone therapy in diabetic patients with foot ulcers. Oxid Med Cell Longev:273475. https://doi.org/10.1155/2014/273475

  8. Travagli V, Zanardi I, Bernini P, Nepi S, Tenori L, Bocci V (2010) Effects of ozone blood treatment on the metabolite profile of human blood. Int J Toxicol 29(2):165–174. https://doi.org/10.1177/1091581809360069

    Article  PubMed  CAS  Google Scholar 

  9. Viebahn-hänsler R, Fernández OS, Fahmy Z (2012) Ozone in medicine: the low-dose ozone concept: guidelines and treatment strategies. Ozone Sci Eng 34:408–424. https://doi.org/10.1080/01919512.2012.717847

    Article  CAS  Google Scholar 

  10. Aljohani S, Fliefel R, Ihbe J, Kühnisch J, Ehrenfeld M, Otto S (2017) What is the effect of anti-resorptive drugs (ARDs) on the development of medication-related osteonecrosis of the jaw (MRONJ) in osteoporosis patients: a systematic review. J Craniomaxillofac Surg 45(9):1493–1502. https://doi.org/10.1016/j.jcms.2017.05.028

    Article  PubMed  Google Scholar 

  11. Madrid C, Bouferrache K, Abarca M, Jaques B, Broome M (2010) Bisphosphonate-related osteonecrosis of the jaws: how to manage cancer patients. Oral Oncol 46(6):468–470. https://doi.org/10.1016/j.oraloncology.2010.03.016

    Article  PubMed  CAS  Google Scholar 

  12. Kushner GM, Alpert B (2011) Bisphosphonate-related osteonecrosis of the jaws. Curr Opin Otolaryngol Head Neck Surg 19(4):302–306. https://doi.org/10.1097/MOO.0b013e328348b257

    Article  PubMed  Google Scholar 

  13. Ruggiero SL (2011) Bisphosphonate-related osteonecrosis of the jaw: an overview. Ann N Y Acad Sci 1218:38–46. https://doi.org/10.1111/j.1749-6632.2010.05768.x

    Article  ADS  PubMed  CAS  Google Scholar 

  14. Bone HG, Chapurlat R, Brandi ML, Brown JP, Czerwinski E, Krieg MA, Mellström D, Radominski SC, Reginster JY, Resch H, Ivorra JA, Roux C, Vittinghoff E, Daizadeh NS, Wang A, Bradley MN, Franchimont N, Geller ML, Wagman RB et al (2013) The effect of three or six years of denosumab exposure in women with postmenopausal osteoporosis: results from the FREEDOM extension. J Clin Endocrinol Metab 98(11):4483–4492. https://doi.org/10.1210/jc.2013-1597

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Papapoulos S, Lippuner K, Roux C, Lin CJ, Kendler DL, Lewiecki EM, Brandi ML, Czerwiński E, Franek E, Lakatos P, Mautalen C, Minisola S, Reginster JY, Jensen S, Daizadeh NS, Wang A, Gavin M, Libanati C, Wagman RB, Bone HG (2015) The effect of 8 or 5 years of denosumab treatment in postmenopausal women with osteoporosis: results from the FREEDOM Extension study. Osteoporos Int 26(12):2773–2783. https://doi.org/10.1007/s00198-015-3234-7

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL (2004) Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 62(5):527–534. https://doi.org/10.1016/j.joms.2004.02.004

    Article  PubMed  Google Scholar 

  17. Woodis CB (2008) Once-yearly administered intravenous zoledronic acid for postmenopausal osteoporosis. Ann Pharmacother 42(7):1085–1089. https://doi.org/10.1345/aph.1K652

    Article  PubMed  CAS  Google Scholar 

  18. Pazianas M (2011) Osteonecrosis of the jaw and the role of macrophages. J Natl Cancer Inst 103(3):232–240. https://doi.org/10.1093/jnci/djq516

    Article  PubMed  Google Scholar 

  19. Rasmusson L, Abtahi J (2014) Bisphosphonate associated osteonecrosis of the jaw: an update on pathophysiology, risk factors, and treatment. Int J Dent 2014:471035. https://doi.org/10.1155/2014/471035

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Bagan J, Sáez GT, Tormos MC, Gavalda-Esteve C, Bagan L, Leopoldo-Rodado M, Calvo J, Camps C (2014) Oxidative stress in bisphosphonate-related osteonecrosis of the jaws. J Oral Pathol Med 43(5):371–377. https://doi.org/10.1111/jop.12151

    Article  PubMed  CAS  Google Scholar 

  21. Tamaoka J, Takaoka K, Hattori H, Ueta M, Maeda H, Yamamura M, Yamanegi K, Noguchi K, Kishimoto H (2019) Osteonecrosis of the jaws caused by bisphosphonate treatment and oxidative stress in mice. Exp Ther Med 17(2):1440–1448. https://doi.org/10.3892/etm.2018.7076

    Article  PubMed  CAS  Google Scholar 

  22. Wink DA, Grisham MB, Mitchell JB, Ford PC (1996) Direct and indirect effects of nitric oxide in chemical reactions relevant to biology. Methods Enzymol 268:12–31. https://doi.org/10.1016/s0076-6879(96)68006-9

    Article  PubMed  CAS  Google Scholar 

  23. Bilge A, Öztürk Ö, Adali Y, Üstebay S (2018) Could ozone treatment be a promising alternative for osteomyelitis? An experimental study. Acta Ortop Bras 26(1):67–71. https://doi.org/10.1590/1413-785220182601179926

    Article  PubMed  PubMed Central  Google Scholar 

  24. Oguz E, Ekinci S, Eroglu M, Bilgic S, Koca K, Durusu M, Kaldirim U, Sadir S, Yurttas Y, Cakmak G, Kilic A, Purtuloglu T, Ozyurek S, Cekli Y, Ozkan H, Sehirlioglu A (2011) Evaluation and comparison of the effects of hyperbaric oxygen and ozonized oxygen as adjuvant treatments in an experimental osteomyelitis model. J Surg Res 171(1):e61–e68. https://doi.org/10.1016/j.jss.2011.06.029

    Article  PubMed  CAS  Google Scholar 

  25. Yasheng T, Mijiti A, Yushan M, Liu Z, Liu Y, Yusufu A (2021) Ozonated water lavage and physiological saline irrigation combined with vacuum-sealed drainage in the treatment of 18 cases of chronic osteomyelitis. J Int Med Res 49(3):300060521999530. https://doi.org/10.1177/0300060521999530

    Article  PubMed  CAS  Google Scholar 

  26. Agrillo A, Ungari C, Filiaci F, Priore P, Iannetti G (2007) Ozone therapy in the treatment of avascular bisphosphonate-related jaw osteonecrosis. J Craniofac Surg 18(5):1071–1075. https://doi.org/10.1097/scs.0b013e31857261f

    Article  PubMed  Google Scholar 

  27. Agrillo A, Filiaci F, Ramieri V, Riccardi E, Quarato D, Rinna C, Gennaro P, Cascino F, Mitro V, Ungari C (2012) Bisphosphonate-related osteonecrosis of the jaw (BRONJ): 5 year experience in the treatment of 131 cases with ozone therapy. Eur Rev Med Pharmacol Sci 16(12):1741–1747

    PubMed  CAS  Google Scholar 

  28. Ripamonti CI, Cislaghi E, Mariani L, Maniezzo M (2011) Efficacy and safety of medical ozone (O(3)) delivered in oil suspension applications for the treatment of osteonecrosis of the jaw in patients with bone metastases treated with bisphosphonates: preliminary results of a phase I-II study. Oral Oncol 47(3):185–190. https://doi.org/10.1016/j.oraloncology.2011.01.002

    Article  PubMed  CAS  Google Scholar 

  29. Goker F, Donati G, Grecchi F, Sparaco A, Ghezzi M, Rania V, Rossi CA, Del Fabbro M (2020) Treatment of BRONJ with ozone/oxygen therapy and debridement with piezoelectric surgery. Eur Rev Med Pharmacol Sci 24(17):9094–9103. https://doi.org/10.26355/eurrev_202009_22855

    Article  PubMed  CAS  Google Scholar 

  30. Maluf G, Caldas RJ, Fregnani ER, da Silva Santos PS (2019) A rare case of bevacizumab-related osteonecrosis of the jaw associated with dental implants. Int J Implant Dent 5(1):34. https://doi.org/10.1186/s40729-019-0188-0

    Article  PubMed  PubMed Central  Google Scholar 

  31. Petrucci MT, Gallucci C, Agrillo A, Mustazza MC, Foà R (2007) Role of ozone therapy in the treatment of osteonecrosis of the jaws in multiple myeloma patients. Haematologica 92(9):1289–1290. https://doi.org/10.3324/haematol.11096

    Article  PubMed  Google Scholar 

  32. Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG (2010) Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol 8(6):e1000412. https://doi.org/10.1371/journal.pbio.1000412

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Hadad H, Kawamata de Jesus L, Piquera Santos AF, Rinaldi Matheus H, Souza Rodrigues LG, Paolo Poli P, Marcantonio Junior E, Pozzi Semeghini Guastaldi F, Maiorana C, Milanezi de Almeida J, Okamoto R, Ávila Souza F (2022) Beta tricalcium phosphate, either alone or in combination with antimicrobial photodynamic therapy or doxycycline, prevents medication-related osteonecrosis of the jaw. Sci Rep 12:16510. https://doi.org/10.1038/s41598-022-20128-4

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  34. Curra, C., Cardoso, C. L., Ferreira, O., Júnior, Curi, M. M., Matsumoto, M. A., Cavenago, B. C., dos Santos, P. L., & Santiago, J. F., Júnior (2016). Medication-related osteonecrosis of the jaw. Introduction of a new modified experimental model. Acta Cir Bras, 31(5), 308–313. doi: https://doi.org/10.1590/S0102-865020160050000003

  35. Erdemci F, Gunaydin Y, Sencimen M, Bassorgun I, Ozler M, Oter S, Gulses A, Gunal A, Sezgin S, Bayar GR, Dogan N, Gider IK (2014) Histomorphometric evaluation of the effect of systemic and topical ozone on alveolar bone healing following tooth extraction in rats. Int J Oral Maxillofac Surg 43(6):777–783. https://doi.org/10.1016/j.ijom.2013.12.007

    Article  PubMed  CAS  Google Scholar 

  36. Koçer G, Nazıroğlu M, Çelik Ö, Önal L, Özçelik D, Koçer M, Sönmez TT (2013) Basic fibroblast growth factor attenuates bisphosphonate-induced oxidative injury but decreases zinc and copper levels in oral epithelium of rat. Biol Trace Elem Res 153(1-3):251–256. https://doi.org/10.1007/s12011-013-9659-y

    Article  PubMed  CAS  Google Scholar 

  37. Howie RN, Borke JL, Kurago Z, Daoudi A, Cray J, Zakhary IE, Brown TL, Raley JN, Tran LT, Messer R, Medani F, Elsalanty ME (2015) A model for osteonecrosis of the jaw with zoledronate treatment following repeated major trauma. PloS One 10(7):e0132520. https://doi.org/10.1371/journal.pone.0132520

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Janovszky Á, Szabó A, Varga R, Garab D, Boros M, Mester C, Beretka N, Zombori T, Wiesmann HP, Bernhardt R, Ocsovszki I, Balázs P, Piffkó J (2015) Periosteal microcirculatory reactions in a zoledronate-induced osteonecrosis model of the jaw in rats. Clin Oral Investig 19(6):1279–1288. https://doi.org/10.1007/s00784-014-1347-6

    Article  PubMed  Google Scholar 

  39. Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, Müller R (2010) Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res 25(7):1468–1486. https://doi.org/10.1002/jbmr.141

    Article  PubMed  Google Scholar 

  40. Dempster DW, Compston JE, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR, Parfitt AM (2013) Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 28(1):2–17. https://doi.org/10.1002/jbmr.1805

    Article  PubMed  Google Scholar 

  41. Awodele O, Olayemi SO, Nwite JA, Adeyemo TA (2012) Investigation of the levels of oxidative stress parameters in HIV and HIV-TB co-infected patients. J Infect Dev Ctries 6(1):79–85. https://doi.org/10.3855/jidc.1906

    Article  PubMed  CAS  Google Scholar 

  42. Lebreton F, van Schaik W, Sanguinetti M, Posteraro B, Torelli R, Le Bras F, Verneuil N, Zhang X, Giard JC, Dhalluin A, Willems RJ, Leclercq R, Cattoir V (2012) AsrR is an oxidative stress sensing regulator modulating Enterococcus faecium opportunistic traits, antimicrobial resistance, and pathogenicity. PLoS Pathog 8(8):e1002834. https://doi.org/10.1371/journal.ppat.1002834

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. McDevitt CA, Ogunniyi AD, Valkov E, Lawrence MC, Kobe B, McEwan AG, Paton JC (2011) A molecular mechanism for bacterial susceptibility to zinc. PLoS Pathog 7(11):e1002357. https://doi.org/10.1371/journal.ppat.1002357

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Pacheco VN, Langie R, Etges A, Ponzoni D, Puricelli E (2015) Nitrogen-containing bisphosphonate therapy: assessment of the alveolar bone structure in rats - a blind randomized controlled trial. Int J Exp Pathol 96(4):255–260. https://doi.org/10.1111/iep.12133

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Lopes Castro MM, Nascimento PC, Souza-Monteiro D, Santos SM, Arouck MB, Garcia VB, Araújo RF Jr, de Araujo AA, Balbinot GS, Collares FM, Rosing CK, Monteiro MC, Ferraz Maia CS, Lima RR (2020) Blood oxidative stress modulates alveolar bone loss in chronically stressed rats. Int J Mol Sci 21(10):3728. https://doi.org/10.3390/ijms21103728

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Domazetovic V, Marcucci G, Iantomasi T, Brandi ML, Vincenzini MT (2017) Oxidative stress in bone remodeling: role of antioxidants. Clin Cases Miner Bone Metab 14(2):209–216. https://doi.org/10.11138/ccmbm/2017.14.1.209

    Article  PubMed  PubMed Central  Google Scholar 

  47. Walter C, Pabst A, Ziebart T, Klein M, Al-Nawas B (2011) Bisphosphonates affect migration ability and cell viability of HUVEC, fibroblasts and osteoblasts in vitro. Oral Dis 17(2):194–199. https://doi.org/10.1111/j.1601-0825.2010.01720.x

    Article  PubMed  CAS  Google Scholar 

  48. Gao SY, Zheng GS, Wang L, Liang YJ, Zhang SE, Lao XM, Li K, Liao GQ (2017) Zoledronate suppressed angiogenesis and osteogenesis by inhibiting osteoclasts formation and secretion of PDGF-BB. PLoS One 12(6):e0179248. https://doi.org/10.1371/journal.pone.0179248

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. T.L. Pires, Efeito da ozonioterapia sistêmica em ratos em uso de bisfosfonato. (2018). 62 f., il. Dissertação (Mestrado em Ciências da Saúde)—Universidade de Brasília, Brasília.

  50. León OS, Menéndez S, Merino N, Castillo R, Sam S, Pérez L, Cruz E, Bocci V (1998) Ozone oxidative preconditioning: a protection against cellular damage by free radicals. Mediators Inflamm 7(4):289–294. https://doi.org/10.1080/09629359890983

    Article  PubMed  PubMed Central  Google Scholar 

  51. Okamoto T, de Russo MC (1973) Wound healing following tooth extraction. Histochemical study in rats. Rev Fac Odontol Aracatuba 2(2):153–169

    PubMed  CAS  Google Scholar 

  52. Okamoto T, Okamoto R, Alves Rezende MC, Gabrielli MF (1994) Interference of the blood clot on granulation tissue formation after tooth extraction. Histomorphological study in rats. Braz Dent J 5(2):85–92

    PubMed  CAS  Google Scholar 

  53. Broughton G 2nd, Janis JE, Attinger CE (2006) Wound healing: an overview. Plast Reconstr Surg 117(7 Suppl). https://doi.org/10.1097/01.prs.0000222562.60260.f9

  54. Lang M, Zhou Z, Shi L, Niu J, Xu S, Lin W, Chen Z, Wang Y (2016) Influence of zoledronic acid on proliferation, migration, and apoptosis of vascular endothelial cells. Br J Oral Maxillofac Surg 54(8):889–893. https://doi.org/10.1016/j.bjoms.2016.05.030

    Article  PubMed  CAS  Google Scholar 

  55. Pan J, Pilawski I, Yuan X, Arioka M, Ticha P, Tian Y, Helms JA (2020) Interspecies comparison of alveolar bone biology: tooth extraction socket healing in mini pigs and mice. J Periodontol 91(12):1653–1663. https://doi.org/10.1002/JPER.19-0667

    Article  PubMed  CAS  Google Scholar 

  56. Pilawski I, Tulu US, Ticha P, Schüpbach P, Traxler H, Xu Q, Pan J, Coyac BR, Yuan X, Tian Y, Liu Y, Chen J, Erdogan Y, Arioka M, Armaro M, Wu M, Brunski JB, Helms JA (2021) Interspecies comparison of alveolar bone biology, part I: morphology and physiology of pristine bone. JDR Clin Transl Res 6(3):352–360. https://doi.org/10.1177/2380084420936979

    Article  CAS  Google Scholar 

  57. Hadad H, Matheus HR, Pai SI, Souza FA, Guastaldi FPS (2023) Rodents as an animal model for studying tooth extraction-related medication-related osteonecrosis of the jaw: assessment of outcomes. Arch Oral Biol 159:105875. https://doi.org/10.1016/j.archoralbio.2023.105875

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank Ozone&Life for providing the ozone generator to carry out this research.

Funding

MPS was funded by CAPES, Finance Code 001—Coordination for the Improvement of Higher Education Personnel, and FAS was funded by CNPQ—National Council for Scientific and Technological Development (Process 409327/2021-2). The authors would like to thank Brazilian Federal Agency for Support and Evaluation of Graduate Education (CAPES), within the scope of the Program CAPES-Print; process number #88887.899731/2023-00; Multiuser Laboratory at FOA/UNESP (FINEP 01.12.0530.00—PROINFRA 01/2011), where micro-CT was performed; and the confocal fluorescence microscopy laboratory at FOAr/Unesp (FINEP 01/2008, #01.09.0313.00—REF 0349/2009).

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Author notes

  1. Henrique Hadad, Laís Kawamata de Jesus, Maria Eduarda de Freitas Santana Oliveira, Juliano Milanezi Almeida, Heloisa Helena Nímia, Osvaldo Magro Filho, Roberta Okamoto, Sérgio Bruzadelli Macedo, Celso Fernando Palmieri Junior, and Francisley Ávila Souza contributed equally to this work.

Authors and Affiliations

  1. Department of Diagnosis and Surgery, Araçatuba Dental School, São Paulo State University (UNESP), José Bonifácio Street, 1193, Vila Mendonça, Araçatuba, São Paulo, 16015050, Brazil

    Maísa Pereira-Silva, Henrique Hadad, Laís Kawamata de Jesus, Maria Eduarda de Freitas Santana Oliveira, Juliano Milanezi de Almeida, Osvaldo Magro Filho & Francisley Ávila Souza

  2. Department of Dental Materials and Prothesis, Araçatuba Dental School, São Paulo State University (UNESP), José Bonifácio Street, Araçatuba, São Paulo, 16015050, Brazil

    Heloisa Helena Nímia

  3. Department of Basic Sciences, Araçatuba Dental School, São Paulo State University (UNESP), Marechal Rondon Highway, Araçatuba, São Paulo, 16066840, Brazil

    Roberta Okamoto

  4. Department of Dentistry, University of Brasília (UnB), Asa Norte, Brasília, Distrito Federal, 70297-400, Brazil

    Sérgio Bruzadelli Macedo

  5. Department of Oral & Maxillofacial Surgery, Louisiana State University Health Sciences Center (LSU), Kings Highway, Shreveport, LA, 71103, USA

    Celso Fernando Palmieri Junior

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Contributions

M.P.S., H.H., S.B.M., and F.A.S. contributed to the conception or design of the work; M.P.S., L.K.J., M.E.F.S.O., S.B.M., H.H.N., and J.M.A. contributed to the acquisition of the material; M.P.S., J.M.A., and F.A.S. contributed to interpretation of data. M.P.S. and F.A.S. drafted the work; F.A.S., J.M.A., C.F.P.J., O.M.F., and R.O. revised it critically for important intellectual content. All authors approved the version to be published and all authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Maísa Pereira-Silva or Francisley Ávila Souza.

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All experimental protocols were approved by the Ethical Committee for Animal Use (CEUA) of the Araçatuba School of Dentistry, UNESP (CEUA 0236-2021).

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Pereira-Silva, M., Hadad, H., de Jesus, L.K. et al. Ozone therapy effect in medication-related osteonecrosis of the jaw as prevention or treatment: microtomographic, confocal laser microscopy and histomorphometric analysis. Clin Oral Invest 28, 151 (2024). https://doi.org/10.1007/s00784-024-05547-z

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