Effect of self-assembling peptide P11-4 on orthodontic treatment-induced carious lesions

A Welk, A Ratzmann, M Reich, K F Krey, Ch Schwahn, A Welk, A Ratzmann, M Reich, K F Krey, Ch Schwahn

Abstract

This study aimed to evaluate the effect of self-assembling peptide P11-4 (SAP) in the therapy of initial smooth surface caries (white spot lesions, WSL) following orthodontic multibracket treatment. Twenty-three patients (13f/10m; average age 15.4 years) with at least two teeth with WSL were recruited for the randomised controlled clinical trial with split-mouth design. In opposite to the control teeth, the test teeth were treated with SAP on Day 0. The primary endpoint was the impedance measurement of WSL using customised tray to ensure reproducibility of the measurement location. The secondary endpoint was the morphometric measurement of WSL using a semi-automated approach to determine the WSL size in mm2. Treatment effects were adjusted for site-specific baseline values using mixed models adapted from the cross-over design. Test WSL showed a mean baseline impedance value of 46.7, which decreased to 21.1, 18.4, and 19.7 after 45, 90, and 180 days, respectively. Control WSL showed a mean baseline value of 42.0, which decreased to 35.0, 29.5, and 33.7, respectively. The overall treatment contrast was -13.7 (95% CI: -19.6 - -7.7; p < 0.001). For the secondary endpoint, the test WSL size decreased from 8.8 at baseline to 6.5 after 180 days. The control WSL decreased from 6.8 to 5.7, respectively. The related treatment contrast was -1.0 in favour of test WSL (95% CI: -1.6 - -0.5; p = 0.004). The treatment of initial carious lesions with self-assembling peptide P11-4 leads to superior remineralisation of the subsurface lesions compared with the control teeth.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Impedance measurement of White Spot Lesion at different time points (black: test tooth/grey: control tooth). As “temporally and logically, a baseline cannot be a response to treatment, so baseline and response cannot be modeled in an integrated framework”, baseline and response were graphed differently. Consequently, the response and the 95% CI are adjusted for baseline values. p = 0.001, p = 0.005, and p = 0.007 for treatment differences after 45, 90, and 180 days, respectively.
Figure 2
Figure 2
Morphometric measurement of White Spot Lesion Size in mm2 at different time points (black: test tooth/grey: control tooth). As “temporally and logically, a baseline cannot be a response to treatment, so baseline and response cannot be modeled in an integrated framework”, baseline and response were graphed differently. Consequently, the response and the 95% CI are adjusted for baseline values. p = 0.969, p = 0.137, and p = 0.004 for treatment differences after 45, 90, and 180 days, respectively.
Figure 3
Figure 3
Patient Flow Chart.
Figure 4
Figure 4
Image of Impedance measurement of WSL with CarieScan Pro (Orangedental/Biberach/Germany).
Figure 5
Figure 5
Overview image of Morphometric measurement of WSL with Shadepilot (DeguDent/Hanau/Germany).
Figure 6
Figure 6
Computer Screen image of Morphometric measurement of WSL with Shadepilot (DeguDent/Hanau/Germany).

References

    1. Staudt CB, Lussi A, Jacquet J, Kiliaridis S. White spot lesions around brackets: in vitro detection by laser fluorescence. Eur J Oral Sci. 2004;112:237–243. doi: 10.1111/j.1600-0722.2004.00133.x.
    1. Mattousch TJ, van der Veen MH, Zentner A. Caries lesions after orthodontic treatment followed by quantitative light-induced fluorescence: a 2-year follow-up. Eur J Orthod. 2007;29:294–298. doi: 10.1093/ejo/cjm008.
    1. Höchli D, Hersberger-Zurfluh M, Papageorgiou SN, Eliades T. Interventions for orthodontically induced white spot lesions: a systematic review and meta-analysis. Eur J Orthod. 2017;39:122–133. doi: 10.1093/ejo/cjw065.
    1. Ren Y, Jongsma MA, Mei L, van der Mei HC, Busscher HJ. Orthodontic treatment with fixed appliances and biofilm formation–a potential public health threat? Clin Oral Investig. 2014;18:1711–1718. doi: 10.1007/s00784-014-1240-3.
    1. Gorelick L, Geiger AM, Gwinnett AJ. Incidence of white spot formation after bonding and banding. Am J Orthod. 1982;81:93–98. doi: 10.1016/0002-9416(82)90032-X.
    1. Richter AE, Arruda AO, Peters MC, Sohn W. Incidence of caries lesions among patients treated with comprehensive orthodontics. Am J Orthod Dentofacial Orthop. 2011;139:657–664. doi: 10.1016/j.ajodo.2009.06.037.
    1. Featherstone JDB, Chaffee BW. The Evidence for Caries Management by Risk Assessment (CAMBRA(R)) Adv Dent Res. 2018;29:9–14. doi: 10.1177/0022034517736500.
    1. Gao SS, Zhang S, Mei ML, Lo EC, Chu CH. Caries remineralisation and arresting effect in children by professionally applied fluoride treatment - a systematic review. BMC Oral Health. 2016;16:12. doi: 10.1186/s12903-016-0171-6.
    1. Petersson LG, Twetman S, Pakhomov GN. The efficiency of semiannual silane fluoride varnish applications: a two-year clinical study in preschool children. J Public Health Dent. 1998;58:57–60. doi: 10.1111/j.1752-7325.1998.tb02991.x.
    1. de Oliveira BH, Dos Santos AP. Semiannual Fluoride Applications in Low-Risk Toddlers May Not Be More Effective Than Toothbrushing Instruction and Dietary Counseling in Controlling Dental Caries. J Evid Based Dent Pract. 2016;16:246–248. doi: 10.1016/j.jebdp.2016.11.006.
    1. de Oliveira, P. R., Fonseca, A. B., Silva, E. M., Coutinho, T. C. & Tostes, M. A. Remineralizing potential of CPP-ACP cremes with and without fluoride in artificial enamel lesions. Aust Dent J, 10.1111/adj.12305 (2015).
    1. Muller F, et al. Elemental depth profiling of fluoridated hydroxyapatite: saving your dentition by the skin of your teeth? Langmuir. 2010;26:18750–18759. doi: 10.1021/la102325e.
    1. Bergman G, Lind PO. A quantitative microradiographic study of incipient enamel caries. J Dent Res. 1966;45:1477–1484. doi: 10.1177/00220345660450053701.
    1. Pandya M, Diekwisch TGH. Enamel biomimetics-fiction or future of dentistry. Int J Oral Sci. 2019;11:8. doi: 10.1038/s41368-018-0038-6.
    1. Rechmann P, Chaffee BW, Rechmann BMT, Featherstone JDB. Changes in Caries Risk in a Practice-Based Randomized Controlled Trial. Adv Dent Res. 2018;29:15–23. doi: 10.1177/0022034517737022.
    1. Urquhart, O. et al. Nonrestorative Treatments for Caries: Systematic Review and Network Meta-analysis. J Dent Res, 22034518800014, 10.1177/0022034518800014 (2018).
    1. Fernandez-Ferrer L, et al. Enamel remineralization therapies for treating postorthodontic white-spot lesions: A systematic review. J Am Dent Assoc. 2018;149:778–786 e772. doi: 10.1016/j.adaj.2018.05.010.
    1. 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;75:175–190. doi: 10.1007/s00056-014-0211-2.
    1. Amaechi BT. Remineralisation - the buzzword for early MI caries management. Br Dent J. 2017;223:173–182. doi: 10.1038/sj.bdj.2017.663.
    1. Alkilzy M, Santamaria RM, Schmoeckel J, Splieth CH. Treatment of Carious Lesions Using Self-Assembling Peptides. Adv Dent Res. 2018;29:42–47. doi: 10.1177/0022034517737025.
    1. Philip N. State of the Art Enamel Remineralization Systems: The Next Frontier in Caries Management. Caries Res. 2018;53:284–295. doi: 10.1159/000493031.
    1. Jablonski-Momeni A, et al. Randomised in situ clinical trial investigating self-assembling peptide matrix P11-4 in the prevention of artificial caries lesions. Sci Rep. 2019;9:269. doi: 10.1038/s41598-018-36536-4.
    1. Kind L, et al. Biomimetic Remineralization of Carious Lesions by Self-Assembling Peptide. J Dent Res. 2017;96:790–797. doi: 10.1177/0022034517698419.
    1. Kirkham, J. et al. Self-assembling peptide scaffolds promote enamel remineralization. J Dent Res86, 426–430, 86/5/426 (2007).
    1. Brunton PA, et al. Treatment of early caries lesions using biomimetic self-assembling peptides - a clinical safety trial. Br Dent J. 2013;215:E6. doi: 10.1038/sj.bdj.2013.741.
    1. Mannaa, A., Sedlakova, P., Bommer, C., di Bella, E. & Krejci, I. In IADR Vol. 96th General Session (London, GB, 2018).
    1. Bröseler, F. et al. Randomised clinical trial investigating self-assembling peptide P11-4 in the treatment of early caries. Clin Oral Investig, 10.1007/s00784-019-02901-4 (2019).
    1. Nyvad B, Baelum V. Nyvad Criteria for Caries Lesion Activity and Severity Assessment: A Validated Approach for Clinical Management and Research. Caries Res. 2018;52:397–405. doi: 10.1159/000480522.
    1. Mortensen, D., Gizani, S., Salamara, O., Sifakakis, I. & Twetman, S. Monitoring regression of post-orthodontic lesions with impedance spectroscopy: a pilot study. Eur J Orthod, 10.1093/ejo/cjy075 (2018).
    1. Longbottom C, Huysmans MC, Pitts NB, Los P, Bruce PG. Detection of dental decay and its extent using a.c. impedance spectroscopy. Nat Med. 1996;2:235–237. doi: 10.1038/nm0296-235.
    1. Cohen, J. E. The association between CarieScan Pro readings and histologic depth of caries in non cavitated occlusal lesion in vitro. MS (Master of Science) thesis, University of Iowa, (2013).
    1. Alkilzy M, Tarabaih A, Santamaria RM, Splieth CH. Self-assembling Peptide P11-4 and Fluoride for Regenerating Enamel. J Dent Res. 2018;97:148–154. doi: 10.1177/0022034517730531.
    1. Tassery H, et al. Use of new minimum intervention dentistry technologies in caries management. Aust Dent J. 2013;58(Suppl 1):40–59. doi: 10.1111/adj.12049.
    1. Schmidlin P, Zobrist K, Attin T, Wegehaupt F. In vitro re-hardening of artificial enamel caries lesions using enamel matrix proteins or self-assembling peptides. J Appl Oral Sci. 2016;24:31–36. doi: 10.1590/1678-775720150352.
    1. Kamal D, Hassanein H, Elkassas D, Hamza H. Comparative evaluation of remineralizing efficacy of biomimetic self-assembling peptide on artificially induced enamel lesions: An in vitro study. J Conserv Dent. 2018;21:536–541. doi: 10.4103/JCD.JCD_123_18.
    1. Pandis N, Chung B, Scherer RW, Elbourne D, Altman DG. CONSORT 2010 statement: extension checklist for reporting within person randomised trials. BMJ. 2017;357:j2835. doi: 10.1136/bmj.j2835.
    1. Pearl, J. Causality. Models, Reasoning, and Inference. 2nd edn, (Cambridge University Press, 2009).
    1. Harrell, F. E., Jr. & Slaughter, J. C. In Biostatistics for Biomedical Research (2001–2019).
    1. Lesaffre E, Philstrom B, Needleman I, Worthington H. The design and analysis of split-mouth studies: what statisticians and clinicians should know. Stat Med. 2009;28:3470–3482. doi: 10.1002/sim.3634.
    1. Hujoel PP, Loesche WJ. Efficiency of split-mouth designs. J Clin Periodontol. 1990;17:722–728. doi: 10.1111/j.1600-051x.1990.tb01060.x.
    1. Kenward MG, Roger JH. Small sample inference for fixed effects from restricted maximum likelihood. Biometrics. 1997;53:983–997. doi: 10.2307/2533558.
    1. Committee for Proprietary Medicinal Products (CPMP). Points to consider on adjustment for baseline covariates. Statistics in Medicine23, 701–709, 10.1002/sim.1647 (2004).
    1. Harrell, F. E., Jr. Regression modeling strategies. With applications to linear models, logistic and ordinal regression, and survival analysis. 2nd edn, ix, 5, 19, 104, (Springer, 2015).
    1. Wasserstein LR, Lazar NA. The ASA’s Statement on p-Values: Context, Process, and Purpose. The American Statistician. 2016;70:129–133. doi: 10.1080/00031305.2016.1154108.
    1. Takahashi F, et al. Ultrasonic assessment of the effects of self-assembling peptide scaffolds on preventing enamel demineralization. Acta Odontol Scand. 2016;74:142–147. doi: 10.3109/00016357.2015.1066850.
    1. Wierichs RJ, Kogel J, Lausch J, Esteves-Oliveira M, Meyer-Lueckel H. Effects of Self-Assembling Peptide P11-4, Fluorides, and Caries Infiltration on Artificial Enamel Caries Lesions in vitro. Caries Res. 2017;51:451–459. doi: 10.1159/000477215.
    1. Krejci I, Lieber CM, Lutz F. Time required to remove totally bonded tooth-colored posterior restorations and related tooth substance loss. Dent Mater. 1995;11:34–40. doi: 10.1016/0109-5641(95)80006-9.
    1. Senn, S. Cross-over Trials in Clinical Research. 2nd edn, (John Wiley & Sons, Ltd, 2002).
    1. Boersma JG, van der Veen MH, Lagerweij MD, Bokhout B, Prahl-Andersen B. Caries prevalence measured with QLF after treatment with fixed orthodontic appliances: influencing factors. Caries Res. 2005;39:41–47. doi: 10.1159/000081655.
    1. van der Veen MH, Attin R, Schwestka-Polly R, Wiechmann D. Caries outcomes after orthodontic treatment with fixed appliances: do lingual brackets make a difference? Eur J Oral Sci. 2010;118:298–303. doi: 10.1111/j.1600-0722.2010.00733.xEOS733.
    1. Greenland S, et al. Statistical tests, P values, confidence intervals, and power: a guide to misinterpretations. Eur J Epidemiol. 2016;31:337–350. doi: 10.1007/s10654-016-0149-3.
    1. Jones, B. & Kenward, M. G. Design and Analysis of Cross-Over Trials. 3rd edn, (CRC Press, 2015).

Source: PubMed

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