International Journal of Dental Research & Development (IJDRD) ISSN(P): 2250-2386; ISSN(E): 2321-0117 Vol. 5, Issue 2, Aug 2015, 13-20 TJPRC Pvt. Ltd. EFFECT OF NANO-HYDROXYAPATITE ON REMINERALIZATION OF ENAMEL-A SYSTEMATIC REVIEW NITHIN M. G 1 & JOSEPH JOHN 2 1 Senior Lecturer, Department of Public Health Dentistry, Madha Dental College & Hospital, Kundrathur, Chennai, Tamil Nadu, India 2 Professor & Head, Department of Public Health Dentistry, Saveetha Dental College & Hospital, Chennai, Tamil Nadu, India ABSTRACT The application of nano hydroxyapatite in the repair of early carious lesion has received considerable attention. Neither the remineralization effect nor the protective mechanism has been comprehensibly investigated and has been left to an open debate still. The primary objective of this review was to evaluate the remineralization potential of a toothpaste containing nano hydroxyapatite on early carious lesions of enamel. The Cochrane database of systematic reviews, PubMed, LILACS / BBO, MEDLINE, SCIENCE DIRECT, electronic retrieval systems and databases were selected for identification of studies. Ten in-vitro studies were found in the search, of which only 5 studies met the inclusion criteria. Of the studies included, 3 studies provided data on surface micro hardness, 2 studies for comparison of lesion depth and 2 studies provided data for comparison of loss in mineral content. Results of the review showed that nano hydroxyapatite paste was effective in reducing the initial carious lesions of enamel and can be used as an alternative to fluoridated toothpastes. KEYWORDS: Dentifrice, Nano-Hydroxyapatite, Enamel Remineralization INTRODUCTION Dental caries is a complex disease that affects a large proportion of the world s population, regardless of gender, age and ethnicity. 1 Caries is not just a disease but instead a disease process. 2 The current concept considers caries as a dynamic and reversible process and is the result of the interplay of a number of etiological factors.the understanding of this basic fact has opened up newer avenues of interception of this disease process through re-mineralization. 3, 4 Demineralization and remineralization is a dynamic process and is governed by the degree of saturation of oral fluids (saliva and plaque) with respect to apatite minerals. Tooth mineral is composed mainly of calcium and phosphorous. Methods for providing these constituents of mineral to facilitate re-mineralization of teeth have been the backbone for newer re-mineralization strategies. 1 given an appropriate change in conditions; remineralization may become the predominant process, thus leading to lesion repair. 5, 6 Enamel remineralization has been studied for about 100 years, and it has been suggested that the non- invasive treatment of early caries lesions by remineralization has the potential to be the major advance in the clinical management of the disease. 7 Remineralizing agents are dispensed through a variety of ways mainly in the form of restorative material, pit and fissure sealants, dentifrices, chewing gums and mouth rinses. Dentifrices have now been commonly used as a www.tjprc.org editor@tjprc.org
14 Nithin M.G & Joseph John vehicle for remineralizing. Fluoride (F) has been a useful instrument and is one of the most effective remineralizing agents in caries prevention. Nevertheless, some concern has been expressed that with the wide array of both prescription and over-thecounter fluoride products now being marketed in every country, the total fluoride intake has increased to perhaps harmful levels. The prevalence of dental fluorosis, on the other hand, has increased noticeably in non-fluoridated areas and to a lesser extent in optimally fluoridated areas. 8, 9 Therefore, it is still necessary to seek alternative, effective non-fluoride agents that can provide a complete cure for caries. In recent years, alternatives to fluoride such as nanohydroxyapatite (HA) and casein phosphopeptide (CPP) have been proposed for their anticariogenic properties. It has been shown that CPP with calcium and phosphorus, which has a 10, 11 high affinity for the HA of tooth enamel, can enhance tooth remineralization and is safe for clinical use. Nano-hydroxyapatite (n-hap) is considered one of the most biocompatible and bioactive materials, and has gained wide acceptance in medicine and dentistry in recent years. Owing to its chemical and structural similarity with enamel minerals, the application of nano-hydroxyapatite to biomimetic repair the damaged enamel directly have been received great attention in today s dental research. 12 Nanoparticle hydroxyapatite containing toothpastes were first introduced and tested in Japan in the 1980s (e.g. Apadent, Apagard, and others by Sangi Co., Ltd., Tokyo). However, evidence is still incomplete to substantiate claims by manufacturers and so far none of these products have been comparable to fluorides. Therefore, the aim of the present systematic review was to evaluate how effective is the remineralization potential of nanohydroxyapatite toothpaste on enamel. MATERIAL AND METHODS Criteria for Considering Studies for this Review We included studies which tested the re-mineralization potential of nano-hydroxyapatite toothpaste on human enamel. The main inclusion criteria being In-vitro studies Relevant to review objective of the particular nano-hydroxyapatite topic Language of publication comprehensible by the reviewer Studies with parameters like lesion depth, Surface micro hardness and loss of mineral were included for this review. The included articles were reviewed in depth and excluded according to the following criteria: Clinical trials Animal studies Review articles, letter to editors (not containing primary data). Types of Material: The test tooth paste consisted of nano-hydroxyapatite dentifrice and the control mostly in all studies was a Impact Factor(JCC): 1.9876 Index Copernicus Value(ICV): 3.0
Effect of Nano-Hydroxyapatite on Remineralization of Enamel-A Systematic Review 15 fluoridated dentifrices or an equivalent test solution. Types of interventions: n all studies nano-hydroxyapatite toothpaste was used and compared to a test or control group. The studies made use of a similar ph cycling model, which was carried out for a period of 12 days, thought to replicate the oral environment. The teeth were sectioned and the initial carious lesions were created with the help of the demineralizing solution. After which it was treated by the remineralizing agent, either directly by immersing it into slurry of the toothpaste prepared or to a diluted solution mostly in the ratio of 1:3. Following the completion of the ph cycling the specimens were subjected to different tests to analyze various parameters. Types of Outcome Measures The primary outcome was to see the effect of nano-hydroxyapatite toothpaste on re-mineralization of enamel. Clinical parameters like difference in Lesion depth, Surface micro hardness and loss of mineral content (baseline and posttest) were assessed. Search Methods for Identification of Studies A comprehensive literature search of the following databases were done which included studies of the Cochrane database of systematic reviews, PubMed, LILACS / BBO, MEDLINE, SCIENCE DIRECT. We also searched websites of product manufacturers, as well as Google scholar. The following Electronic Search key Words Materials: nano-hydroxyapatite, nano-hydroxyapatite toothpaste, nano-hydroxyapatite dentifrice, toothpaste and dentifrice Measures: Tooth re-mineralization and Enamel re-mineralization Variables of interest Lesion depth, Surface micro hardness and Loss of mineral content (baseline and post-test). Figure 1 depicts the search strategy used in the present systematic review. A final review of five studies was done Data collection and analysis The records retrieved by the searches were screened for potential relevance against stated inclusion criteria and the following information was extracted from each study: Lesion Depth, Surface micro hardness and mineral loss (baseline and post-test). RESULTS This report aimed to review the in-vitro trials of nano-hydroxyapatite dentifrices used in dentistry. Five studies (in vitro) were identified that focused on remineralization of early carious lesions of enamel. All of the studies showed that nano-hydroxyapatite toothpaste was effective in remineralizing early enamel when comparing with control group. The studies, which assessed the re-mineralization potential of nano-hydroxyapatite toothpaste on enamel were, the studies carried out by S.B. Huang et al 2009, Itthagarun et al 2010, Shengbin et al 2010, Peter et al 2011, S. Huang et al www.tjprc.org editor@tjprc.org
16 Nithin M.G & Joseph John 2011. Three studies included had surface micro hardness as outcome measurements (S.B. Huang et al 2009, Shengbin et al 2010 and S. Huang et al 2011). Two studies included had lesion depth as outcomes measurements (Itthagarun et al 2010, Peter et al 2011) and two studies included assessed loss of mineral content at baseline to post-test. (Itthagarun et l 2010, Peter et al 2011). For all the three studies which measured the surface micro hardness (S.B. Huang et al 2009, Shengbin et al 2010 and S. Huang et al 2011) there was a significant improvement in hardness of the enamel surface following the use of nanohydroxyapatite paste and for the two studies used for assessment of lesion depth there was a significant improvement in the studies by Peter et al and Itthagarun et al. Increase in mineral content after treatment with nano-hydroxyapatite paste was evident in the study of Peter et al 2011 while no significance was found to be in the study of Itthagarun et al 2010. Given the high proportion of heterogeneity present in the studies reported, a sensitivity analysis was performed using a randomeffects model. The level of evidence of included studies was of evidence level III (In-vitro studies). DISCUSSIONS While the healing effects of fluoride containing toothpastes are well established only limited literature, as seen in this review, exists assessing the re-mineralization potential of nano-hydroxyapatite toothpaste on enamel. The results of the studies included for review showed that hydroxyapatite toothpaste produced similar results to the positive control and also exhibited similar ability to reduce the progress of demineralization, while simultaneously enhancing the artificial caries like lesions. The surface chemical properties and morphological structure of hydroxyapatite has been claimed to play the most important part in re-mineralization of early caries lesions. Three studies showed significant improvement in surface micro hardness post treatment with nano-hydroxyapatite toothpaste (S.B. Huang et al 2009, Shengbin et al 2010 and S. Huang et al 2011) similar to a review by Kim et al 2007. 19 Evidences from the studies (Itthagarun et al 2010, Peter et al 2011) has shown that lesions can be re-hardened by deposition of hydroxyapatite that is initially deposited near the surface layer of the enamel and this was found to be significant. Future studies are required for further assessment of the potential of nano-hydroxyapatite toothpaste on enamel in-vivo. CONCLUSIONS Given the small number of experiments and limitations of the in-vitro studies comparing the re-mineralizing potential of nano-hydroxyapatite toothpaste on enamel, the effectiveness of this toothpaste seems to be obvious in improving the initial enamel carious lesions. More research is needed to be carried out with clinical studies to substantiate the effectiveness of nano-hydroxyapatite on enamel. REFERENCES 1. Hicks J, Garcia-Godoy F, Flaitz C. Biological factors in dental caries: role of remineralization and fluoride in the dynamic process of demineralization and remineralization (part 3). Journal of Clinical Pediatric Dentistry 2004: 28:203-14. Impact Factor(JCC): 1.9876 Index Copernicus Value(ICV): 3.0
Effect of Nano-Hydroxyapatite on Remineralization of Enamel-A Systematic Review 17 2. Featherstone JDB. The science and practice of caries prevention. Journal of American Dental Association 2000: 131:887-99. 3. Kawasaki. K, Ruben.J, Tsuda.H, Huysmans. M.C.D. and Takagi.O. Relationship between Mineral Distributions in Dentine Lesions and Subsequent Remineralization in vitro. Caries Research 2000:34:395-403. 4. Burwell A.K., Litkowski L.J., and Greenspan D.C. Calcium Sodium Phospho silicate (NovaMin ): Remineralization Potential. Advanced Dental Research 2009:21:35-39. 5. Pearce EI, Moore AJ. Remineralization of softened bovine enamel following treatment of overlying plaque with a mineral-enriching solution. Journal of Dental Research 1985: 64:416 21. 6. Kielbassa AM, Mu ller J, Gernhardt CR. Closing the gap between oral hygiene and minimally invasive dentistry: a review on the resin infiltration technique of incipient (proximal) enamel lesions. Quintessence International 2009: 40:663 81 7. Reynolds EC. Calcium phosphate-based remineralization systems: scientific evidence? Australian Dental Journal. 2008: 53(3):268-73. 8. Pendrys D G. Dental fluorosis in perspective Journal of American Dental Association 1991:122:63 6. 9. Newbrun E. Current regulations and recommendations concerning water fluoridation, fluoride supplements, and topical fluoride agents Journal of Dental Research 1992: 1255 65. 10. Reynolds EC. Remineralization of enamel subsurface lesions by casein phosphopeptide-stabilized calcium phosphate solutions. Journal of Dental Research 1997: 76:1587-95. 11. Zhang L, Li Z, Dong Y. Experimental study of phosphopeptide in promoting tooth remineralization. Chinese Journal of Dental Research 2000: 3:27-30. 12. Li L, Pan HH, Tao JH, Xu XR, Mao CY, Gu XH, et al. Repair of enamel by using hydroxyapatite nanoparticles as the building blocks. Journal of Materials Chemistry 2008: 18:4079 84. 13. Huang S B, Gao S S and H Y Yu. Effect of nano-hydroxyapatite concentration on remineralization of initial enamel lesion in vitro. Biomedical Materials 2009: 4:034104. 14. Anut Itthagarun, Nigel Martyn King, Yuen-Man Cheung.The effect of nano-hydroxyapatite toothpaste on artificial enamel carious lesion progression: an in-vitro ph-cycling study. Hong Kong Dental Journal 2010: 7:61-6. 15. Shengbin Huang, Shanshan Gao, Lei Cheng, Haiyang Yu.Combined effects of nano-hydroxyapatite and Galla chinensis on remineralization of initial enamel lesion in vitro. Journal of dentistry, 2010:38: 811-819. 16. Peter Tschoppe, Daniela L. Zandim, Peter Martus, Andrej M. Kielbassa. Enamel and dentine remineralization by nano-hydroxyapatite toothpastes. Journal of dentistry, 2011:39: 430-437. 17. Huang S, Gao L, Cheng H Yu. Remineralization Potential of Nano-Hydroxyapatite on Initial Enamel Lesions: An in vitro Study. Caries Research 2011: 45:460 468. 18. Kim M Y, Kwon H K, Choi C H and Kim B I. Combined effects of nano-hydroxyapatite and NaF on www.tjprc.org editor@tjprc.org
18 Nithin M.G & Joseph John APPENDICES remineralization of early caries lesion. Key Engineering Material 2007:330 332. Table 1: Characteristics of Studies Included for Review Table 2: Characteristics of Excluded Studies STUDY Kani T 1988 Kani T 1989 S.H. Jeong 2006 Syozi Nakashima 2009 Najibfard K 2011 OUTCOMES Article in Japanese Language, so not able to be reviewed Article in Japanese Language, so not able to be reviewed Toothpaste containing micron sized HA was not used as control Used a test dentifrice containing nano sized calcium carbonate In vivo study.intra-oral appliance used, quantification by micro radiography not clear Impact Factor(JCC): 1.9876 Index Copernicus Value(ICV): 3.0
Effect of Nano-Hydroxyapatite on Remineralization of Enamel-A Systematic Review 19 Figure 1: Search Strategy www.tjprc.org editor@tjprc.org