Research advances in treatment of tooth agenesis

doi:10.12337/zgkqzzxzz.2024.06.006

Abstract

Abstract: Tooth agenesis is the most common dental developmental anomaly in humans, which can cause significant chewing, pronunciation, aesthetic and craniofacial development problems. Due to the unique characteristics of tooth agenesis, its treatment is very time-consuming and costly, imposing huge economic burdens and mental stress on patients. The treatments include a sequential therapeutic strategy with a multidisciplinary team of pediatric dentistry, prosthodontics, oral and maxillofacial surgery, orthodontics, oral implantology, and other backgrounds, as well as emerging methods such as targeted molecular therapy and tissue engineering. This review provides an update on the knowledge on the characteristics of tooth agenesis, traditional treatments, and the rising fields of molecular therapy and tissue engineering. We also discuss the treatment effects of each method, aiming to provide a reference for the treatment of tooth agenesis.

Key words: Tooth agenesis, Multidisciplinary and sequential treatment, Dental implants, Molecular targeted therapy, Tooth regeneration

Geng Chenxin, Liu Yang, Han Dong. Research advances in treatment of tooth agenesis[J]. Chinese Journal of Oral Implantology, 2024, 29(3): 224-230.

References

[1] Rakhshan V, Rakhshan H.Meta-analysis of congenitally missing teeth in the permanent dentition: prevalence, variations across ethnicities, regions and time[J]. Int Orthod, 2015, 13(3):261-273. DOI: 10.1016/j.ortho.2015.06.008.
[2] Rakhshan V, Rakhshan A.Systematic review and meta-analysis of congenitally missing permanent dentition: sex dimorphism, occurrence patterns, associated factors and biasing factors[J]. Int Orthod, 2016, 14(3):273-294. DOI: 10.1016/j.ortho.2016.07.016.
[3] Meaney S, Anweigi L, Ziada H, et al.The impact of hypodontia: a qualitative study on the experiences of patients[J]. Eur J Orthod, 2012, 34(5):547-552. DOI: 10.1093/ejo/cjr061.
[4] Johal A, Huang Y, Toledano S.Hypodontia and its impact on a young person's quality of life, esthetics, and self-esteem[J]. Am J Orthod Dentofacial Orthop, 2022, 161(2):220-227. DOI: 10.1016/j.ajodo.2020.07.039.
[5] Murdock S, Lee JY, Guckes A, et al.A costs analysis of dental treatment for ectodermal dysplasia[J]. J Am Dent Assoc, 2005, 136(9):1273-1276. DOI: 10.14219/jada.archive.2005.0343.
[6] Behr M, Proff P, Leitzmann M, et al.Survey of congenitally missing teeth in orthodontic patients in eastern Bavaria[J]. Eur J Orthod, 2011, 33(1):32-36. DOI: 10.1093/ejo/cjq021.
[7] Khalaf K, Miskelly J, Voge E, et al.Prevalence of hypodontia and associated factors: a systematic review and meta-analysis[J]. J Orthod, 2014, 41(4):299-316. DOI: 10.1179/1465313314Y.0000000116.
[8] Gokkaya B, Oflezer OG, Ozdil NY, et al.Is there any relationship between hypodontia and hyperdontia with taurodontism, microdontia and macrodontia? A retrospective study[J]. Niger J Clin Pract, 2020, 23(6):805-810. DOI: 10.4103/njcp.njcp_559_19.
[9] Kirzioğlu Z, Köseler Sentut T, Ozay Ertürk MS, et al.Clinical features of hypodontia and associated dental anomalies: a retrospective study[J]. Oral Dis, 2005, 11(6):399-404. DOI: 10.1111/j.1601-0825.2005.01138.x.
[10] Haselden K, Hobkirk JA, Goodman JR, et al.Root resorption in retained deciduous canine and molar teeth without permanent successors in patients with severe hypodontia[J]. Int J Paediatr Dent, 2001, 11(3):171-178. DOI: 10.1046/j.1365-263x.2001.00257.x.
[11] Bjerklin K, Bennett J.The long-term survival of lower second primary molars in subjects with agenesis of the premolars[J]. Eur J Orthod, 2000, 22(3):245-255. DOI: 10.1093/ejo/22.3.245.
[12] Bjerklin K, Kurol J, Valentin J.Ectopic eruption of maxillary first permanent molars and association with other tooth and developmental disturbances[J]. Eur J Orthod, 1992, 14(5):369-375. DOI: 10.1093/ejo/14.5.369.
[13] Chan DW, Samman N, McMillan AS. Craniofacial profile in Southern Chinese with hypodontia[J]. Eur J Orthod, 2009, 31(3):300-305. DOI: 10.1093/ejo/cjn111.
[14] Chung LK, Hobson RS, Nunn JH, et al.An analysis of the skeletal relationships in a group of young people with hypodontia[J]. J Orthod, 2000, 27(4):315-318. DOI: 10.1093/ortho/27.4.315.
[15] Takahashi Y, Higashihori N, Yasuda Y, et al.Examination of craniofacial morphology in Japanese patients with congenitally missing teeth: a cross-sectional study[J]. Prog Orthod, 2018, 19(1):38. DOI: 10.1186/s40510-018-0238-9.
[16] Wang H, Hung K, Zhao K, et al.Anatomical analysis of zygomatic bone in ectodermal dysplasia patients with oligodontia[J]. Clin Implant Dent Relat Res, 2019, 21(2):310-316. DOI: 10.1111/cid.12731.
[17] Seifi M, Walter MA.Axenfeld-Rieger syndrome[J]. Clin Genet, 2018, 93(6):1123-1130. DOI: 10.1111/cge.13148.
[18] Gill DS, Barker CS.The multidisciplinary management of hypodontia: a team approach[J]. Br Dent J, 2015, 218(3):143-149. DOI: 10.1038/sj.bdj.2015.52.
[19] Rana S, Orloff C, I Bomfim D, et al. The role of the general dental practitioner in the management of the hypodontia patient[J]. Br Dent J, 2023, 235(7):522-524. DOI: 10.1038/s41415-023-6326-3.
[20] Nunn JH, Carter NE, Gillgrass TJ, et al.The interdisciplinary management of hypodontia: background and role of paediatric dentistry[J]. Br Dent J, 2003, 194(5):245-251. DOI: 10.1038/sj.bdj.4809925.
[21] Patano A, Inchingolo AM, Laudadio C, et al.Therapeutic strategies of primary molar infraocclusion: a systematic review[J]. Children (Basel), 2023, 10(3):582. DOI: 10.3390/children10030582.
[22] Carter NE, Gillgrass TJ, Hobson RS, et al.The interdisciplinary management of hypodontia: orthodontics[J]. Br Dent J, 2003, 194(7):361-366. DOI: 10.1038/sj.bdj.4809995.
[23] Kokich VO Jr, Kinzer GA.Managing congenitally missing lateral incisors. Part I: Canine substitution[J]. J Esthet Restor Dent, 2005, 17(1):5-10. DOI: 10.1111/j.1708-8240.2005.tb00076.x.
[24] Silveira GS, de Almeida NV, Pereira DM, et al. Prosthetic replacement vs space closure for maxillary lateral incisor agenesis: a systematic review[J]. Am J Orthod Dentofacial Orthop, 2016, 150(2):228-237. DOI: 10.1016/j.ajodo.2016.01.018.
[25] Fekonja A.Hypodontia in orthodontically treated children[J]. Eur J Orthod, 2005, 27(5):457-460. DOI: 10.1093/ejo/cji027.
[26] Dueled E, Gotfredsen K, Trab Damsgaard M, et al.Professional and patient-based evaluation of oral rehabilitation in patients with tooth agenesis[J]. Clin Oral Implants Res, 2009, 20(7):729-736. DOI: 10.1111/j.1600-0501.2008.01698.x.
[27] Rachmiel A, Turgeman S, Emodi O, et al.Management of severely atrophic maxilla in ectrodactyly ectodermal dysplasia-cleft syndrome[J]. Plast Reconstr Surg Glob Open, 2018, 6(2):e1678. DOI: 10.1097/GOX.0000000000001678.
[28] Goel P, Fahradyan A, Wolfswinkel EM, et al.Is Le Fort I distraction enough to treat severe midface hypoplasia?[J]. J Craniofac Surg, 2021, 32(5):1716-1720. DOI: 10.1097/SCS.0000000000007448.
[29] Durey K, Cook P, Chan M.The management of severe hypodontia. Part 1: Considerations and conventional restorative options[J]. Br Dent J, 2014, 216(1):25-29. DOI: 10.1038/sj.bdj.2013.1236.
[30] Schnabl D, Grunert I, Schmuth M, et al.Prosthetic rehabilitation of patients with hypohidrotic ectodermal dysplasia: a systematic review[J]. J Oral Rehabil, 2018, 45(7):555-570. DOI: 10.1111/joor.12638.
[31] Varghese AA, Xavier AM, Ramanarayanan V. Removable prosthetic management for tooth agenesis in the pediatric population: a systematic review of case reports and case series[J]. J Prosthet Dent, 2023: S0022-3913(23)00105-00101. DOI: 10.1016/j.prosdent.2023.02.005.
[32] Kutkut A, Bertoli E, Frazer R, et al.A systematic review of studies comparing conventional complete denture and implant retained overdenture[J]. J Prosthodont Res, 2018, 62(1):1-9. DOI: 10.1016/j.jpor.2017.06.004.
[33] Laverty DP, Fairbrother K, Addison O.The current evidence on retaining or prosthodontically replacing retained deciduous teeth in the adult hypodontia patient: a systematic review[J]. Eur J Prosthodont Restor Dent, 2018, 26(1):2-15. DOI: 10.1922/EJPRD_01721Laverty14.
[34] Terheyden H, Wüsthoff F.Occlusal rehabilitation in patients with congenitally missing teeth-dental implants, conventional prosthetics, tooth autotransplants, and preservation of deciduous teeth-a systematic review[J]. Int J Implant Dent, 2015, 1(1):30. DOI: 10.1186/s40729-015-0025-z.
[35] Filius M, Vissink A, Cune MS, et al.Effect of implant therapy on oral health-related quality of life (OHIP-49), health status (SF-36), and satisfaction of patients with several agenetic teeth: prospective cohort study[J]. Clin Implant Dent Relat Res, 2018, 20(4):592-597. DOI: 10.1111/cid.12625.
[36] Casaña-Ruiz MD, Català-Pizarro M, Borrás-Aviñó C, et al.Implants as a treatment alternative in children with multiple agnesia: systematic review and meta-analysis[J]. J Clin Exp Dent, 2023, 15(4):e324-e337. DOI: 10.4317/jced.60168.
[37] Wu Y, Wang XD, Wang F, et al.Restoration of oral function for adult edentulous patients with ectodermal dysplasia: a prospective preliminary clinical study[J]. Clin Implant Dent Relat Res, 2015, 17(Suppl 2):e633-e642. DOI: 10.1111/cid.12296.
[38] 刘晶, 赵凯, 王旭东, 等. 外胚层发育不全缺牙患者种植修复临床效果[J]. 口腔疾病防治, 2018, 26(7):451-455. DOI: 10.12016/j.issn.2096-1456.2018.07.008.
[39] 蒋欣珂, 喻康, 周梦琪, 等. 重度先天缺牙患者WNT10A基因新突变位点的检测及其种植修复[J]. 口腔疾病防治
2022,30(10):724-732. DOI: 10.12016/j.issn.2096-1456.2022.10.007.
[40] Filius M, Cune MS, Koopmans PC, et al.Dental implants with fixed prosthodontics in oligodontia: a retrospective cohort study with a follow-up of up to 25 years[J]. J Prosthet Dent, 2018, 120(4):506-512. DOI: 10.1016/j.prosdent.2017.12.009.
[41] Pjetursson BE, Thoma D, Jung R, et al.A systematic review of the survival and complication rates of implant-supported fixed dental prostheses (FDPs) after a mean observation period of at least 5 years[J]. Clin Oral Implants Res, 2012, 23(Suppl 6):22-38. DOI: 10.1111/j.1600-0501.2012.02546.x.
[42] Filius MA, Cune MS, Raghoebar GM, et al.Prosthetic treatment outcome in patients with severe hypodontia: a systematic review[J]. J Oral Rehabil, 2016, 43(5):373-387. DOI: 10.1111/joor.12384.
[43] Atieh MA, Alsabeeha NH, Faggion CM Jr, et al.The frequency of peri-implant diseases: a systematic review and meta-analysis[J]. J Periodontol, 2013, 84(11):1586-1598. DOI: 10.1902/jop.2012.120592.
[44] Filius M, Vissink A, Cune MS, et al.Long-term implant performance and patients' satisfaction in oligodontia[J]. J Dent, 2018, 71:18-24. DOI: 10.1016/j.jdent.2018.01.007.
[45] Blume O, Donkiewicz P, Back M, et al.Bilateral maxillary augmentation using CAD/CAM manufactured allogenic bone blocks for restoration of congenitally missing teeth: a case report[J]. J Esthet Restor Dent, 2019, 31(3):171-178. DOI: 10.1111/jerd.12454.
[46] Gaide O, Schneider P.Permanent correction of an inherited ectodermal dysplasia with recombinant EDA[J]. Nat Med, 2003, 9(5):614-618. DOI: 10.1038/nm861.
[47] Casal ML, Lewis JR, Mauldin EA, et al.Significant correction of disease after postnatal administration of recombinant ectodysplasin A in canine X-linked ectodermal dysplasia[J]. Am J Hum Genet, 2007, 81(5):1050-1056. DOI: 10.1086/521988.
[48] Körber I, Klein OD, Morhart P, et al.Safety and immunogenicity of Fc-EDA, a recombinant ectodysplasin A1 replacement protein, in human subjects[J]. Br J Clin Pharmacol, 2020, 86(10):2063-2069. DOI: 10.1111/bcp.14301.
[49] Schneider H, Faschingbauer F, Schuepbach-Mallepell S, et al.Prenatal correction of X-linked hypohidrotic ectodermal dysplasia[J]. N Engl J Med, 2018, 378(17):1604-1610. DOI: 10.1056/NEJMoa1714322.
[50] Schneider H, Schweikl C, Faschingbauer F, et al.A causal treatment for X-linked hypohidrotic ectodermal dysplasia: long-term results of short-term perinatal ectodysplasin A1 replacement[J]. Int J Mol Sci, 2023, 24(8):7155. DOI: 10.3390/ijms24087155.
[51] Schneider H, Hadj-Rabia S, Faschingbauer F, et al.Protocol for the phase 2 EDELIFE trial investigating the efficacy and safety of intra-amniotic ER004 administration to male subjects with X-linked hypohidrotic ectodermal dysplasia[J]. Genes (Basel), 2023, 14(1):153. DOI: 10.3390/genes14010153.
[52] Kowalczyk C, Dunkel N, Willen L, et al.Molecular and therapeutic characterization of anti-ectodysplasin A receptor (EDAR) agonist monoclonal antibodies[J]. J Biol Chem, 2011, 286(35):30769-30779. DOI: 10.1074/jbc.M111.267997.
[53] Del-Pozo J, MacIntyre N, Azar A, et al. Role of ectodysplasin signalling in middle ear and nasal pathology in rat and mouse models of hypohidrotic ectodermal dysplasia[J]. Dis Model Mech, 2019, 12(4):dmm037804. DOI: 10.1242/dmm.037804.
[54] Kowalczyk-Quintas C, Schuepbach-Mallepell S, Willen L, et al.Pharmacological stimulation of edar signaling in the adult enhances sebaceous gland size and function[J]. J Invest Dermatol, 2015, 135(2):359-368. DOI: 10.1038/jid.2014.382.
[55] Murashima-Suginami A, Kiso H, Tokita Y, et al. Anti-USAG-1 therapy for tooth regeneration through enhanced BMP signaling[J]. Sci Adv, 2021, 7(7):eabf1798. DOI: 10.1126/sciadv.abf1798.
[56] Chen FM, Gao LN, Tian BM, et al.Treatment of periodontal intrabony defects using autologous periodontal ligament stem cells: a randomized clinical trial[J]. Stem Cell Res Ther, 2016, 7:33. DOI: 10.1186/s13287-016-0288-1.
[57] Nakashima M, Iohara K, Murakami M, et al.Pulp regeneration by transplantation of dental pulp stem cells in pulpitis: a pilot clinical study[J]. Stem Cell Res Ther, 2017, 8(1):61. DOI: 10.1186/s13287-017-0506-5.
[58] Alaohali A, Salzlechner C, Zaugg LK, et al.GSK3 inhibitor-induced dentinogenesis using a hydrogel[J]. J Dent Res, 2022, 101(1):46-53. DOI: 10.1177/00220345211020652.
[59] Ikeda E, Morita R, Nakao K, et al.Fully functional bioengineered tooth replacement as an organ replacement therapy[J]. Proc Natl Acad Sci U S A, 2009, 106(32):13475-13480. DOI: 10.1073/pnas.0902944106.
[60] Ono M, Oshima M, Ogawa M, et al.Practical whole-tooth restoration utilizing autologous bioengineered tooth germ transplantation in a postnatal canine model[J]. Sci Rep, 2017, 7:44522. DOI: 10.1038/srep44522.
[61] Wang F, Wu Z, Fan Z, et al.The cell re-association-based whole-tooth regeneration strategies in large animal, Sus scrofa[J]. Cell Prolif, 2018, 51(4):e12479. DOI: 10.1111/cpr.12479.
[62] Cai J, Zhang Y, Liu P, et al.Generation of tooth-like structures from integration-free human urine induced pluripotent stem cells[J]. Cell Regen, 2013, 2(1):6. DOI: 10.1186/2045-9769-2-6.
[63] Miao X, Niibe K, Fu Y, et al.Epiprofin transcriptional activation promotes ameloblast induction from mouse induced pluripotent stem cells via the BMP-smad signaling axis[J]. Front Bioeng Biotechnol, 2022, 10:890882. DOI: 10.3389/fbioe.2022.890882.
[64] Zhang M, Zhang X, Luo J, et al.Investigate the odontogenic differentiation and dentin-pulp tissue regeneration potential of neural crest cells[J]. Front Bioeng Biotechnol, 2020, 8:475. DOI: 10.3389/fbioe.2020.00475.
[65] Oyanagi T, Takeshita N, Hara M, et al.Insulin-like growth factor 1 modulates bioengineered tooth morphogenesis[J]. Sci Rep, 2019, 9(1):368. DOI: 10.1038/s41598-018-36863-6.