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Effect of root surface treatment with denusomab after delayed tooth replantation

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Abstract

Objectives

To evaluate denosumab, a human monoclonal antibody that mimics the effects of osteoprotegerin in bone metabolism, as a topical treatment of root surface to be used prior to delayed tooth replantation.

Materials and methods

Thirty-six rats’ right incisors were used. Teeth were extracted and divided into: delayed replantation without root surface treatment (control); delayed replantation with root surface treatment with denosumab 60 mg/mL and 30 mg/mL, respectively, for 10 min both experimentals groups. After that, the root canals were filled with calcium hydroxide and replanted. After 15 and 60 days, the animals were euthanized, and the samples were collected and processed for microscopic analysis. Histological sections were performed, and stained with HE to describe the dental characteristics, measure ankylosis, replacement resorption, and dental resorption by conventional microscopy. Also, was performed Brown & Brenn staining and immunohistochemistry for RANKL, OPG, and periostin.

Results

Denosumab 60 mg/mL reducted ankylosis (p < 0.0001), replacement resorption (p < 0.0001), and tooth resorption, 60 days after replantation, compared to untreated replanted teeth (p < 0.005). Lower bacterial contamination in root surface in the denosumab treatment groups was found, regardless of the concentration used (p < 0.001). Also, denosumab treatment inhibited the expression of RANKL without modulating OPG. Periostin was observed in periodontal ligament of replanted tooth, although this labelling was absent in the ankylosis areas, in both experimental periods.

Conclusion

Treatment of the root surface with denosumab at 60 mg/mL of rat teeth before delayed replantation reduced dental root resorption compared with the untreated teeth after 60 days.

Clinical relevance

Survival of a replanted tooth has been a challenge in clinical practice. The use of a medication, such as denosumab, to limit dental root resorption represents an important therapeutical approach.

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References

  1. Glendor U, Halling A, Andersson L, Eilert-Petersson E (1996) Incidence of traumatic tooth injuries in children and adolescents in the county of Västmanland, Sweden. Swed Dent J 20:15–28

    PubMed  Google Scholar 

  2. Andreasen JO, Bakland LK, Matras RC, Andreasen FM (2006) Traumatic intrusion of permanent teeth. Part 1. An epidemiological study of 216 intruded permanent teeth. Dent Traumatol 22:83–89

    PubMed  Google Scholar 

  3. Andreasen JO, Andreasen FM (2007) Avulsions. In: Andreasen JO, Andreasen FM, Andersson L (eds) Textbook and color atlas of traumatic injuries to the teeth, 4th edn. Oxford, Wiley-Blackwell, pp 444–488

    Google Scholar 

  4. Andreasen JO (1970) Etiology and pathogenesis of traumatic dental injuries. A clinical study of 1298 cases. Scand J Dent Res 78:329–342

    PubMed  Google Scholar 

  5. Andreasen JO, Borum MK, Andreasen FM (1995) Replantation of 400 avulsed permanent incisors. 3. Factors related to root growth. Endod Dent Traumatol 11:69–75

    PubMed  Google Scholar 

  6. Fouad AF, Abbott PV, Tsilingaridis G, et al. International Association of Dental Traumatology guidelines for the management of traumatic dental injuries: 2. Avulsion of permanent teeth [published online ahead of print, 2020 May 27]. Dent Traumatol. 2020;10.1111/edt.12573.

  7. Andersson L, Andreasen JO, Day P, Heithersay G, Trope M, Diangelis AJ, Kenny DJ, Sigurdsson A, Bourguignon C, Flores MT, Hicks ML, Lenzi AR, Malmgren B, Moule AJ, Tsukiboshi M, International Association of Dental Traumatology (2012) International Association of Dental Traumatology. Guidelines for the management of traumatic dental injuries: 2. Avulsion of permanent teeth. Dent Traumatol 28:88–96

    PubMed  Google Scholar 

  8. Kargul B, Welbury R (2009) An audit of the time to initial treatment in avulsion injuries. Dent Traumatol 25:123–125

    PubMed  Google Scholar 

  9. Poi WR, Sonoda CK, Martins CM, Melo ME, Pellizzer EP, de Mendonça MR et al (2013) Storage media for avulsed teeth: a literature review. Braz Dent J 24:437–445

    PubMed  Google Scholar 

  10. Trope M (2011) Avulsion of permanent teeth: theory to practice. Dent Traumatol 27:281–294

    PubMed  Google Scholar 

  11. Andersson L, Blomlöf L, Lindskog S, Feiglin B, Hammarström L (1984) Tooth ankylosis. Clinical, radiographic and histological assessments. Int J Oral Surg 13:423–431

    PubMed  Google Scholar 

  12. Hammarström L, Pierce A, Blomlöf L, Feiglin B, Lindskog S (1986) Tooth avulsion and replantation--a review. Endod Dent Traumatol 2:1–8

    PubMed  Google Scholar 

  13. Barrett EJ, Kenny DJ (1997) Avulsed permanent teeth: a review of the literature and treatment guidelines. Endod Dent Traumatol 13:153–163

    PubMed  Google Scholar 

  14. Ne RF, Witherspoon DE, Gutmann JL (1999) Tooth resorption. Quintessence Int 30:9–25

    PubMed  Google Scholar 

  15. Panzarini SR, Trevisan CL, Brandini DA, Poi WR, Sonoda CK, Luvizuto ER, dos Santos CLV (2012) Intracanal dressing and root canal filling materials in tooth replantation: a literature review. Dent Traumatol 28:42–48

    PubMed  Google Scholar 

  16. Kwan SC, Johnson JD, Cohenca N (2012) The effect of splint material and thickness on tooth mobility after extraction and replantation using a human cadaveric model. Dent Traumatol 28:277–281

    PubMed  Google Scholar 

  17. Lindskog S, Pierce AM, Blomlof L, Hammarstrom L (1985) The role of the necrotic periodontal membrane in cementum resorption and ankylosis. Endod Dent Traumatol 1:96–101

    PubMed  Google Scholar 

  18. Andreasen JO, Borum MK, Jacobsen HL, Andreasen FM (1995) Replantation of 400 avulsed permanent incisors. 4. Factors related to periodontal ligament healing. Endod Dent Traumatol 11:76–89

    PubMed  Google Scholar 

  19. Panzarini SR, Perri de Carvalho AC, Poi WR, Sonoda CK (2005) Use of vitamin C in delayed tooth replantation. Braz Dent J 16:17–22

    PubMed  Google Scholar 

  20. Poi WR, Carvalho RM, Panzarini SR, Sonoda CK, Manfrin TM, Rodrigues TS (2007) Influence of enamel matrix derivative (Emdogain) and sodium fluoride on the healing process in delayed tooth replantation: histologic and histometric analysis in rats. Dent Traumatol 23:35–41

    PubMed  Google Scholar 

  21. Loo WT, Dou YD, Chou WK, Wang M (2008) Thymosin alpha 1 provides short-term and long-term benefits in the reimplantation of avulsed teeth: a double-blind randomized control pilot study. Am J Emerg Med 26:574–577

    PubMed  Google Scholar 

  22. Panzarini SR, Nonato CC, Gulinelli JL, Poi WR, Sonoda CK, Saito CT et al (2014) Effect of the treatment of root surface-adhered necrotic periodontal ligament with propolis or fluoride in delayed rat tooth replantation. Clin Oral Investig 18:1329–1333

    PubMed  Google Scholar 

  23. Zanetta-Barbosa D, Moura CC, Machado JR, Crema VO, Lima CA, de Carvalho AC (2014) Effect of indomethacin on surface treatment and intracanal dressing of replanted teeth in dogs. J Oral Maxillofac Surg 72:127

    PubMed  Google Scholar 

  24. Yoo JE, Kim MS, Kwon YD, Kim EC, Kim KC, Choi SC (2015) Could zoledronic acid prevent root resorption in replanted rat molar? Dent Traumatol 31:465–470

    PubMed  Google Scholar 

  25. Karayilmaz H, Kirzioglu Z, Erken Gungor O (2013) Aetiology, treatment patterns and long-term outcomes of tooth avulsion in children and adolescents. Pak J Med Sci 29:464–468

    PubMed  PubMed Central  Google Scholar 

  26. Bastos JV, Côrtes MI, Silva JF, Goulart EM, Colosimo EA, Gomez RS et al (2015) A study of the interleukin-1 gene cluster polymorphisms and inflammatory external root resorption in replanted permanent teeth. Int Endod J 48:878–887

    PubMed  Google Scholar 

  27. Heymann MF, Riet A, Le Goff B, Battaglia S, Paineau J, Heymann D (2008) OPG, RANK and RANK ligand expression in thyroid lesions. Regul Pept 148:46–53

    PubMed  Google Scholar 

  28. Scagliotti GV, Hirsh V, Siena S, Henry DH, Woll PJ, Manegold C, Solal-Celigny P, Rodriguez G, Krzakowski M, Mehta ND, Lipton L, García-Sáenz JA, Pereira JR, Prabhash K, Ciuleanu TE, Kanarev V, Wang H, Balakumaran A, Jacobs I (2012) Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: subgroup analysis from a randomized phase 3 study. J Thorac Oncol 7(12):1823–1829

    PubMed  Google Scholar 

  29. Curioni-Fontecedro A, Husmann L, Soldini D, Stahel RA (2013) Primary non-small cell lung cancer response upon treatment with denosumab. Lung Cancer 82:506–508

    PubMed  Google Scholar 

  30. Silva I, Branco JC (2012) Denosumab: recent update in postmenopausal osteoporosis. Acta Reumatol Port 37:302–313

    PubMed  Google Scholar 

  31. Tanaka S (2013) Regulation of bone destruction in rheumatoid arthritis through RANKL-RANK pathways. World J Orthop 4:1–6

    PubMed  PubMed Central  Google Scholar 

  32. Gokhale SR, Padhye AM (2013) Future prospects of systemic host modulatory agents in periodontal therapy. Br Dent J 214:467–471

    PubMed  Google Scholar 

  33. Hellsing E, Alatli-Kut I, Hammarström L (1993) Experimentally induced dentoalveolar ankylosis in rats. Int Endod J 26:93–98

    PubMed  Google Scholar 

  34. Nishioka M, Shiiya T, Ueno K, Suda H (1998) Tooth replantation in germ-free and conventional rats. Endod Dent Traumatol 14:163–173

    PubMed  Google Scholar 

  35. Ricieri CB, Sonoda CK, Aranega AM, Panzarini SR, Poi WR, Sundefeld ML et al (2009) Healing process of incisor teeth of diabetic rats replanted after storage in milk. Dent Traumatol 25:284–289

    PubMed  Google Scholar 

  36. Saito CT, Gulinelli JL, Panzarini SR, Garcia VG, Okamoto R, Okamoto T et al (2011) Effect of low-level laser therapy on the healing process after tooth replantation: a histomorphometrical and immunohistochemical analysis. Dent Traumatol 27:30–39

    PubMed  Google Scholar 

  37. Vilela RG, Gjerde K, Frigo L, Leal Junior EC, Lopes-Martins RA, Kleine BM et al (2012) Histomorphometric analysis of inflammatory response and necrosis in re-implanted central incisor of rats treated with low-level laser therapy. Lasers Med Sci 27:551–557

    PubMed  Google Scholar 

  38. Sottovia AD, Sonoda CK, Poi WR, Panzarini SR, Lauris JR (2006) Delayed tooth replantation after root surface treatment with sodium hypochlorite and sodium fluoride: histomorphometric analysis in rats. J Appl Oral Sci 14:93–99

    PubMed  PubMed Central  Google Scholar 

  39. Sottovia AD, Sottovia Filho D, Poi WR, Panzarini SR, Luize DS, Sonoda CK (2010) Tooth replantation after use of Euro-Collins solution or bovine milk as storage medium: a histomorphometric analysis in dogs. J Oral Maxillofac Surg 68:111–119

    PubMed  Google Scholar 

  40. Engbaek K, Johansen KS, Jensen ME (1979) A new technique for Gram staining paraffin-embedded tissue. J Clin Pathol 32:187–190

    PubMed  PubMed Central  Google Scholar 

  41. Barreiros D, Pucinelli CM, Oliveira KMH, Paula-Silva FWG, Nelson Filho P, Silva LABD et al (2018) Immunohistochemical and mRNA expression of RANK, RANKL, OPG, TLR2 and MyD88 during apical periodontitis progression in mice. J Appl Oral Sci 26:e20170512

    PubMed  PubMed Central  Google Scholar 

  42. Andreasen JO (1975) Periodontal healing after replantation of traumatically avulsed human teeth. Assesment by mobility testing and radiography. Acta Odontol Scand 33:325–335

    Google Scholar 

  43. Andreasen JO, Kristerson L (1981) The effect of limited drying or removal of the periodontal ligament periodontal healing after replantation of mature permanent incisors in monkey. Acta Odont Scand 39:1–13

    PubMed  Google Scholar 

  44. Maslamani M, Almusawi A, Joseph B, Gabato S, Andersson L (2016) An experimental model for studies on delayed tooth replantation and ankylosis in rabbits. Dent Traumatol 32:443–449

    PubMed  Google Scholar 

  45. Alyahya A, Alqareer A (2017) Does the removal of cementum facilitate bacterial penetration into dentinal tubules in vitro? J Endod 43:1111–1115

    PubMed  Google Scholar 

  46. Mori GG, Poi WR, Castilho LR (2013) Evaluation of the anti-resorptive ability of an experimental acetazolamide paste for the treatment of late replanted teeth: a study in rats. Dent Traumatol 29(1):34–40

    PubMed  Google Scholar 

  47. (2018) Policy on prevention of sports-related orofacial injuries. Pediatr Dent 40(6):86–91

  48. Okamoto T, Okamoto R (1995) Interferência da imobilização sobre o processo de reparação após o reimplante imediato de incisivo superior de rato. Estudo histomofológico. Rev Odont UNESP 24:87–98

    Google Scholar 

  49. Gomes WD, Silva CA, Melo ME, Silva VF, Almeida MM, Pedrini D et al (2015) Delayed tooth replantation in rats: effect of systemic antibiotic therapy with amoxicillin and tetracycline. Dent Traumatol 31:448–456

    PubMed  Google Scholar 

  50. Najeeb S, Siddiqui F, Khurshid Z, Zohaib S, Zafar MS, Ansari SA (2017) Effect of bisphosphonates on root resorption after tooth replantation - a systematic review. Dent Traumatol 33:77–83

    PubMed  Google Scholar 

  51. Lustosa-Pereira A, Garcia RB, de Moraes IG, Bernardineli N, Bramante CM, Bortoluzzi EA (2006) Evaluation of the topical effect of alendronate on the root surface of extracted and replanted teeth. Microscopic analysis on rats’ teeth. Dent Traumatol 22:30–35

    PubMed  Google Scholar 

  52. Manfrin TM, Poi WR, Okamoto R, Panzarini SR, Sonoda CK, Saito CT, Hamanaka EF, Martins CM (2013) Expression of OPG, RANK, and RANKL proteins in tooth repair processes after immediate and delayed tooth. J Craniofac Surg 24:e74–e80

    PubMed  Google Scholar 

  53. Longo DL, Paula-Silva FWG, Barbizam JV, Cohenca N, Silva LAB (2016) Reimplante dentário tardio - mediadores envolvidos nas reabsorções inflamatória e de substituição. In: 38a Jornada Odontológica de Ribeirão Preto, 2016, Ribeirão Preto. Anais da Faculdade de Odontologia de Ribeirão Preto da Universidade de São Paulo, 29:107

  54. Panzarini SR, Gulinelli JL, Poi WR, Sonoda CK, Pedrini D, Brandini DA (2008) Treatment of root surface in delayed tooth replantation: a review of literature. Dent Traumatol 24:277–282

    PubMed  Google Scholar 

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Funding

This study was partially supported by grant from São Paulo Research Foundation (FAPESP) 2010/17611-4 to FWGPS. DLL and CMP received a CAPES Fellowship (Financial Code: 000).

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Authors and Affiliations

  1. Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Av. do Café s/n, Ribeirão Preto, SP, 14040-904, Brazil

    Léa Assed Bezerra da Silva, Maria Bernadete Sasso Stuani, Alexandra Mussolino de Queiroz, Raquel Assed Bezerra da Silva, Paulo Nelson-Filho, Heloisa Aparecida Orsini Vieira, Carolina Maschietto Pucinelli & Francisco Wanderley Garcia Paula-Silva

  2. University of Rio Verde, Rio Verde, Goiás, Brazil

    Daniele Lucca Longo

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  1. Léa Assed Bezerra da Silva
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  2. Daniele Lucca Longo
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Correspondence to Raquel Assed Bezerra da Silva.

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da Silva, L.A.B., Longo, D.L., Stuani, M.B.S. et al. Effect of root surface treatment with denusomab after delayed tooth replantation. Clin Oral Invest 25, 1255–1264 (2021). https://doi.org/10.1007/s00784-020-03430-1

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