Remineralisation and Biomimetics: Remineralisation Agents and Fluoride Therapy

  • David J. MantonEmail author
  • Eric C. Reynolds


The demineralisation and remineralisation cycle needs to be controlled in order to prevent the decomposition of dental tissues. The use of fluoridated products, especially the consumption of fluoridated water and use of fluoridated toothpaste, provides significant reduction in caries risk in a cost-effective manner. Fluoride has also been used as a caries-preventive agent in varnishes and gels; for decades anti-fluoride propaganda questioned the public and the dental sector about its safety. Therefore, it is important to discuss the pros and cons of fluoride therapy using scientific evidence. More recently, a number of products containing calcium and phosphate have been released onto the market – these products use a variety of technologies and have varying levels of evidenced-based justification. The mechanisms of action of fluoride- and calcium-based technologies will be discussed in detail.


Carious Lesion Gingival Crevicular Fluid Amorphous Calcium Phosphate Molar Incisor Hypomineralisation Mouth Rinse 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Avery JK. Enamel. In: Steele PF, editor. Essentials of oral histology and embryology. 2nd ed. St Louis: Mosby Inc.; 2000. p. 84–93.Google Scholar
  2. 2.
    Mkhonto D, de Leeuw NH. A computer modelling study of the effect of water on the surface structure and morphology of fluorapatite: introducing a Ca-10(PO4)(6)F-2 potential model. J Mater Chem. 2002;12(9):2633–42.CrossRefGoogle Scholar
  3. 3.
    Marsh PD. Microbial ecology of dental plaque and its significance in health and disease. Adv Dent Res. 1994;8(2):263–71.PubMedGoogle Scholar
  4. 4.
    Kleinberg I. A mixed-bacteria ecological approach to understanding the role of oral bacteria in dental caries causation: an alternative to Streptococcus mutans and the specific plaque hypothesis. Crit Rev Oral Biol Med. 2002;13(2):108–25.PubMedCrossRefGoogle Scholar
  5. 5.
    Beighton D. The complex oral microflora of high-risk individuals and groups and its role in the caries process. Comm Dent Oral Epidemiol. 2005;33:248–55.CrossRefGoogle Scholar
  6. 6.
    Featherstone JDB. Dental caries: a dynamic disease process. Aust Dent J. 2008;53(3):286–91.PubMedCrossRefGoogle Scholar
  7. 7.
    Edgar W, Dawes C, O’Mullane D. Saliva and oral health. 3rd ed. London: British Dental Association; 2004. p. 120–8.Google Scholar
  8. 8.
    Morbidity and Mortality Weekly Report. Fluoridation of drinking water to prevent Dental caries. In: Services Usdohh, editor. Centers of Disease Control as te author – i.e. Centers of Disease Control. Fluoridation of drinking water to prevent dental caries. MMWR. 1999;48(41):933–40.
  9. 9.
    ten Cate JM. Current concepts on the theories of the mechanism of action of fluoride. Acta Odontol Scand. 1999;57(6):325–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Aoba T. Solubility properties of human tooth mineral and pathogenesis of dental caries. Oral Dis. 2004;10(5):249–57.PubMedCrossRefGoogle Scholar
  11. 11.
    Vogel GL, Tenuta LMA, Schumacher GE, Chow LC. No calcium-fluoride-like deposits detected in plaque shortly after a sodium fluoride mouthrinse. Caries Res. 2010;44(2):108–15.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    England PH. Water fluoridation. Health monitoring report for England 2014. London: Department of Health, UK; 2014. Contract No.: 2013547.Google Scholar
  13. 13.
    McDonagh MS, Whiting PF, Wilson PM, Sutton AJ, Chestnutt I, Cooper J, et al. Systematic review of water fluoridation. BMJ. 2000;321(7265):855–9.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Services USDoHaH. U.S. Public Health Service recommendation for fluoride concentration in drinking water for the prevention of dental caries. Public Health Rep. 2015;130:1–14.Google Scholar
  15. 15.
    Cagetti MG, Campus G, Milia E, Lingström P. A systematic review on fluoridated food in caries prevention. Acta Odontol Scand. 2013;71(3–4):381–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Yeung CA, Chong LY, Glenny A-M. Fluoridated milk for preventing dental caries. Cochrane Database Syst Rev. 2015;(9):CD003876. doi: 10.1002/14651858.CD003876.pub4.
  17. 17.
    Tubert-Jeannin S, Auclair C, Amsallem E, Tramini P, Gerbaud L, Ruffieux C, et al. Fluoride supplements (tablets, drops, lozenges or chewing gums) for preventing dental caries in children. Cochrane Database Syst Rev. 2011;(12):CD007592. doi: 10.1002/14651858.CD007592.pub2.
  18. 18.
    Walsh T, Worthington HV, Glenny AM, Appelbe P, Marinho VC, Shi X. Fluoride toothpastes of different concentrations for preventing dental caries in children and adolescents. Cochrane Database Syst Rev. 2010;(1):CD007868.Google Scholar
  19. 19.
    Santos APP, Oliveira BH, Nadanovsky P. Effects of Low and standard fluoride toothpastes on caries and fluorosis: systematic review and meta-analysis. Caries Res. 2013;47(5):382–90.PubMedCrossRefGoogle Scholar
  20. 20.
    Wright JT, Hanson N, Ristic H, Whall CW, Estrich CG, Zentz RR. Fluoride toothpaste efficacy and safety in children younger than 6 years: a systematic review. J Am Dent Assoc. 2014;145(2):182–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Ekstrand KR, Poulsen JE, Hede B, Twetman S, Qvist V, Ellwood RP. A randomized clinical trial of the anti-caries efficacy of 5,000 compared to 1,450 ppm fluoridated toothpaste on root caries lesions in elderly disabled nursing home residents. Caries Res. 2013;47(5):391–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Marinho VCC, Worthington HV, Walsh T, Chong LY. Fluoride gels for preventing dental caries in children and adolescents. Cochrane Database Sys Rev. 2015;(6):CD002280. doi: 10.1002/14651858.CD002280.pub2.
  23. 23.
    Marinho VCC, Higgins JPT, Sheiham A, Logan S. One topical fluoride (toothpastes, or mouthrinses, or gels, or varnishes) versus another for preventing dental caries in children and adolescents. Cochrane Database Syst Rev. 2004;(1):CD002780. doi: 10.1002/14651858.CD002780.pub2.
  24. 24.
    Marinho VCC, Worthington HV, Walsh T, Clarkson JE. Fluoride varnishes for preventing dental caries in children and adolescents. Cochrane Database Syst Rev. 2013;(7):CD002279. doi: 10.1002/14651858.CD002279.pub2.
  25. 25.
    Marinho VC, Worthington HV, Walsh T, Chong LY. Fluoride gels for preventing dental caries in children and adolescents. Cochrane Database Syst Rev. 2015;(6):CD002280.Google Scholar
  26. 26.
    Weintraub JA, Ramos-Gomez F, Jue B, Shain S, Hoover CI, Featherstone JDB, et al. Fluoride varnish efficacy in preventing early childhood caries. J Dent Res. 2006;85(2):172–6.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Shen P, Bagheri R, Walker GD, Yuan Y, Stanton DP, Reynolds C, et al. Effect of calcium phosphate addition to fluoride containing dental varnishes on enamel demineralization. Aust Dent J. 2015. doi: 10.1111/adj.12385.
  28. 28.
    Pithon MM, dos Santos MJ, Andrade CSS, Leão Filho JCB, Braz AKS, de Araujo RE, et al. Effectiveness of varnish with CPP–ACP in prevention of caries lesions around orthodontic brackets: an OCT evaluation. Eur J Orthod. 2015;37(2):177–82.PubMedCrossRefGoogle Scholar
  29. 29.
    Reynolds EC, Cai F, Cochrane NJ, Walker GD, Morgan MV, Reynolds C. Fluoride and casein phosphopeptide-amorphous calcium phosphate. J Dent Res. 2008;87:344–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Services UDoHaH. Statement on the evidence supporting the safety and effectiveness of community water fluoridation. Atlanta: Centers for Disease Control and Prevention; 2015 [cited 2015 10 November].Google Scholar
  31. 31.
    Aoba T, Fejerskov O. Dental fluorosis: chemistry and biology. Crit Rev Oral Biol Med. 2002;13(2):155–70.PubMedCrossRefGoogle Scholar
  32. 32.
    Thylstrup A, Fejerskov O. A scanning electron microscopic and microradiographic study of pits in fluorosed human enamel. Eur J Oral Sci. 1979;87(2):105–14.CrossRefGoogle Scholar
  33. 33.
    Bhagavatula P, Levy SM, Broffitt B, Weber-Gasparoni K, Warren JJ. Timing of fluoride intake and dental fluorosis on late-erupting permanent teeth. Community Dent Oral Epidemiol. 2016;44(1):32–45.PubMedCrossRefGoogle Scholar
  34. 34.
    Pendrys DG, Haugejorden O, Baårdsen A, Wang NJ, Gustavsen F. The risk of enamel fluorosis and caries among Norwegian children: implications for Norway and the United States. J Am Dent Assoc. 2010;141(4):401–14.PubMedCrossRefGoogle Scholar
  35. 35.
    L-s G, Kim YK, Liu Y, Takahashi K, Arun S, Wimmer CE, et al. Immobilization of a phosphonated analog of matrix phosphoproteins within cross-linked collagen as a templating mechanism for biomimetic mineralization. Acta Biomater. 2011;7(1):268–77.CrossRefGoogle Scholar
  36. 36.
    Cochrane NJ, Reynolds EC. Calcium phosphopeptides — mechanisms of action and evidence for clinical efficacy. Adv Dent Res. 2012;24(2):41–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Guggenheim B, Schmid R, Aeschlimann JM, Berrocal R, Neeser JR. Powdered milk micellar casein prevents oral colonization by Streptococcus sobrinus and dental caries in rats: a basis for the caries-protective effect of dairy products. Caries Res. 1999;33(6):446–54.PubMedCrossRefGoogle Scholar
  38. 38.
    Cochrane NJ, Saranathan S, Cai F, Cross KJ, Reynolds EC. Enamel subsurface lesion remineralisation with casein phosphopeptide stabilised solutions of calcium, phosphate and fluoride. Caries Res. 2008;42:88–97.PubMedCrossRefGoogle Scholar
  39. 39.
    Cao Y, Mei ML, Xu J, Lo ECM, Li Q, Chu CH. Biomimetic mineralisation of phosphorylated dentine by CPP-ACP. J Dent. 2013;41(9):818–25.PubMedCrossRefGoogle Scholar
  40. 40.
    Brunton PA, Davies RPW, Burke JL, Smith A, Aggeli A, Brookes SJ, et al. Treatment of early caries lesions using biomimetic self-assembling peptides – a clinical safety trial. Br Dent J. 2013;215(4):E6.
  41. 41.
    Takahashi F, Kurokawa H, Shibasaki S, Kawamoto R, Murayama R, Miyazaki M. Ultrasonic assessment of the effects of self-assembling peptide scaffolds on preventing enamel demineralization. Acta Odontol Scand. 2016;74(2):142–7.Google Scholar
  42. 42.
    Kirkham J, Firth A, Vernals D, Boden N, Robinson C, Shore RC, et al. Self-assembling peptide scaffolds promote enamel remineralization. J Dent Res. 2007;86(5):426–30.PubMedCrossRefGoogle Scholar
  43. 43.
    Jablonski-Momeni A, Heinzel-Gutenbrunner M. Efficacy of the self-assembling peptide P11-4 in constructing a remineralization scaffold on artificially-induced enamel lesions on smooth surfaces. J Orofac Orthop. 2014;75(3):175–90.PubMedCrossRefGoogle Scholar
  44. 44.
    Mangum JE, Crombie FA, Kilpatrick N, Manton DJ, Hubbard MJ. Surface integrity governs the proteome of hypomineralized enamel. J Dent Res. 2010;89(10):1160–5.PubMedCrossRefGoogle Scholar
  45. 45.
    Robinson C, Shore RC, Bonass WA, Brookes SJ, Boteva E, Kirkham J. Identification of human serum albumin in human caries lesions of enamel: the role of putative inhibitors of remineralisation. Caries Res. 1998;32(3):193–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Robinson C, Shore RC, Brookes SJ, Strafford S, Wood SR, Kirkham J. The chemistry of enamel caries. Crit Rev Oral Biol Med. 2000;11(4):481–95.PubMedCrossRefGoogle Scholar
  47. 47.
    Yin W, Hu DY, Fan X, Feng Y, Zhang YP, Cummins D, et al. A clinical investigation using quantitative light-induced fluorescence (QLF) of the anticaries efficacy of a dentifrice containing 1.5% arginine and 1450 ppm fluoride as sodium monofluorophosphate. J Clin Dent. 2013;24 Spec no A:A15–22.Google Scholar
  48. 48.
    Kraivaphan P, Amornchat C, Triratana T, Mateo LR, Ellwood R, Cummins D, et al. Two-year caries clinical study of the efficacy of novel dentifrices containing 1.5% arginine, an insoluble calcium compound and 1,450 ppm fluoride. Caries Res. 2013;47(6):582–90.PubMedCrossRefGoogle Scholar
  49. 49.
    ten Cate JM, Cummins D. Fluoride toothpaste containing 1.5% arginine and insoluble calcium as a new standard of care in caries prevention. J Clin Dent. 2013;24(3):79–87.PubMedGoogle Scholar
  50. 50.
    Burne RA, Marquis RE. Alkali production by oral bacteria and protection against dental caries. FEMS Microbiol Lett. 2000;193(1):1–6.PubMedCrossRefGoogle Scholar
  51. 51.
    Shaw D, Naimi-Akbar A, Astvaldsdottir A. The tribulations of toothpaste trials: unethical arginine dentifrice research. Br Dent J. 2015;219(12):567–9.PubMedCrossRefGoogle Scholar
  52. 52.
    Wefel JS. NovaMin®: likely clinical success. Adv Dent Res. 2009;21(1):40–3.PubMedGoogle Scholar
  53. 53.
    Reynolds EC. Calcium phosphate-based remineralization systems: scientific evidence? Aust Dent J. 2008;53(3):268–73.PubMedCrossRefGoogle Scholar
  54. 54.
    Tschoppe P, Neumann K, Mueller J, Kielbassa AM. Effect of fluoridated bleaching gels on the remineralization of predemineralized bovine enamel in vitro. J Dent. 2009;37(2):156–62.PubMedCrossRefGoogle Scholar
  55. 55.
    Papas A, Russell D, Singh M, Kent R, Triol C, Winston A. Caries clinical trial of a remineralising toothpaste in radiation patients. Gerodontology. 2008;25(2):76–88.PubMedCrossRefGoogle Scholar
  56. 56.
    Burwell A, Jennings D, Muscle D, Greenspan DC. NovaMin and dentin hypersensitivity – in vitro evidence of efficacy. J Clin Dent. 2010;21(3):66–71.PubMedGoogle Scholar
  57. 57.
    Memarpour M, Soltanimehr E, Sattarahmady N. Efficacy of calcium- and fluoride-containing materials for the remineralization of primary teeth with early enamel lesion. Microsc Res Tech. 2015;78(9):801–6.PubMedCrossRefGoogle Scholar
  58. 58.
    Shen P, Manton DJ, Cochrane NJ, Walker GD, Yuan Y, Reynolds C, et al. Effect of added calcium phosphate on enamel remineralization by fluoride in a randomized controlled in situ trial. J Dent. 2011;39(7):518–25.PubMedCrossRefGoogle Scholar
  59. 59.
    Seppä L, Leppänen T, Hausen H. Fluoride varnish versus acidulated phosphate fluoride gel: a 3-year clinical trial. Caries Res. 1995;29(5):327–30.PubMedCrossRefGoogle Scholar
  60. 60.
    Marinho VC, Higgins JP, Logan S, Sheiham A. Systematic review of controlled trials on the effectiveness of fluoride gels for the prevention of dental caries in children. J Dent Educ. 2003;67(4):448–58.PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Elsdon Storey Chair of Child Dental Health, Growth and Development SectionMelbourne Dental School, University of MelbourneParkvilleAustralia
  2. 2.Oral Health Cooperative Research Centre , Melbourne Dental SchoolUniversity of MelbourneMelbourneAustralia

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