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Abstract

Background: Despite improved oral hygiene regime and availability of preventive formulations, dental caries continues to be a global dental problem. Calcium sucrose phosphate (CaSP) is a remineralizing agent with cariostatic action, which is commonly available in the form of tooth cream. Considering the paucity of evidence, this systematic literature review aims to evaluate the remineralizing efficacy of CaSP.

Methodology: The review was conducted as per Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Various databases, including PubMed, Cochrane Central, and Google Scholar, were searched until March 15, 2018 and were assessed for inclusion by two independent reviewers. The primary outcome was to assess the remineralizing efficacy of CaSP, and the secondary outcome was to assess the potential of CaSP in arresting white spot lesion(s) on enamel.

Results: Out of 2,876 articles, only 13 were qualified for inclusion. Included studies presented a low risk of bias for the following items: caries-free teeth or restoration, and adherence to manufacture’s instruction for the usage of remineralizing agent in the risk of bias scale. Ten studies reported an increase in the microhardness of enamel after CaSP application, and three studies reported the effect of CaSP on arresting white spot lesion(s). CaSP was found to be a better remineralizing agent in comparison to casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), casein phosphopeptide-amorphous calcium phosphate with fluoride (CPP-ACPF) and other remineralizing agents in terms of increasing microhardness of enamel. In addition, CaSP application was also found to have a beneficial effect in restoring the color of white spot lesion(s) to that of normal enamel.

Conclusion: CaSP tooth cream was found to be an effective remineralizing agent, compared to others, such as CPP-ACP and CPP-ACPF, in terms of increasing the mean microhardness of enamel and arresting white spot lesion(s).

Keywords

Calcium sucrose phosphate dental caries remineralizing agent remineralization systematic review white spot lesion

Introduction

Dental caries (or cavities) refers to demineralization of enamel, dentin or cementum due to acid production by bacterial communities of Streptococcus mutans, Lactobacillus species, Bifidobacterium, etc.¹ These acids are produced due to the metabolism of dietary carbohydrates which dissolves the mineral component of the tooth and releases calcium and phosphate ions (demineralization).² It continues to be a major oral health problem with a global prevalence of 35%.^{3, 4} National oral health survey reported an overall prevalence ranging between 50% and 84.7% in Indian population.⁵

Multiple factors like smoking, tobacco use, bad oral hygiene, diet, brushing habits and inadequate preventive dental care are associated with high incidence of caries.³ The use of bleaching agents (hydrogen peroxide, carbamide peroxide, etc.) and iron drops constitutes the other common reasons for enamel demineralization.^{6, 7} Consequently, demineralization enhances the porosity of enamel and results in white spot lesion(s) on tooth surface.⁶

Remineralization of enamel, that is, diffusion of calcium and phosphate ions back into crystal voids (created by demineralization) helps in the prevention of dental caries.⁸ Saliva has the ability to remineralize enamel by neutralizing acids produced by dental plaque and maintaining an environment rich with calcium and phosphate ions. However, the remineralization by saliva is a slow process and is insufficient to produce net mineral gain.⁹ Additionally, natural remineralization through saliva has little improvement on the aesthetics and structural properties in the deeper lesions.¹⁰ Hence, there has been a lot of emphasis on enamel remineralization using agents such as calcium sucrose phosphate (CaSP)–calcium orthophosphate complex, casein phosphopeptide–amorphous calcium phosphate (CPP-ACP), calcium sodium phosphosilicate, nano-hydroxyapatite, seed extract, and galla chinensis, which are presently available in different formulations.¹¹

The CaSP, also known as anticay, provides both calcium and phosphate ions in a soluble form in high concentrations.^{2, 6, 12} It is a mixture of 85% by weight of calcium salts of phosphoric acid esters of sucrose and 15% by weight of inorganic calcium orthophosphate.^{2, 13} This combination has a high water solubility index which releases more free calcium and phosphate ions as compared to saliva. Anticay reduces the rate of demineralization of enamel, increases the rate of remineralization by a common ion effect and actively neutralizes the plaque acids.^{6, 13}

Several in vitro studies have compared CaSP with other remineralizing agents and have shown encouraging results with regards to its remineralization potential.^{6, 9, 14} However, no published systematic review explicitly evaluated the remineralizing efficacy of CaSP. Hence, the current systematic review was sought to determine the potential of CaSP as a remineralizing agent in increasing the microhardness of enamel and arresting the white spot lesion(s).

Methods

This systematic review was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines (Supplementary Table 1).¹⁵

Table 1.

Characteristics of Included Studies

Author (Year)	Country	Type of Study	Type of Teeth	Number of Teeth per Group	Remineralizing Agents Used	Primary Outcomes	Conclusion
Aggarwal et al., 2016⁹	India	In vitro	Human premolars without enamel defects	30	Novamin toothpaste in one group CaSP in another group	Evaluate the protective potential of CaSP and novamin-containing toothpaste on enamel surface	Least lesion depth was observed on the enamel surface treated with CaSP
Besten et al., 1995²⁶	United States	In vitro	Human teeth	Normal = 6 Fluorotic = 6 White Spot = 4	CaSP	Assess the impact of CaSP on white spot enamel lesion	CaSP paste application significantly changes the color of fluorotic enamel to that of normal enamel
Gade et al., 2016¹⁹	India	In vitro	Maxillary premolars	Group A = 10 Group B = 10 Group C = 10 Group D = 10	Group A = CaSP Group B = CPP-ACPF Group C = Demineralized only Group D = Sound enamel	Evaluating the enamel remineralizing potential of CPP-ACPF and CaSP using surface microhardness analysis	Microhardness of CaSP and CPP-ACPF was comparable
Gangrade et al., 2016²⁰	India	In vitro	Maxillary premolars	Group A = 10 Group B = 10 Group C = 10 Group D = 10 Group E = 10	Group A = SnF2 Group B = CaSP Group C = CPP-ACPF Group D = Sound enamel Group E = Demineralized only	Evaluate remineralization efficacy of SnF2, CPP-ACPF and CaSP	Application of CaSP, SnF2 and CPP-ACPF showed improved surface remineralization
George et al., 2015¹²	India	In vitro	Non-carious freshly extracted human premolars	Group I = 10 Group II = 10 Group III = 10 Group IV = 10 Group V = 10	Group I = Control Group II = Opalescence 10% Group III = Opalescence PF 10% Group IV = Opalescence 10% with CaSP	Evaluate and compare the microhardness of enamel after anticay (CaSP) application	Mean microhardness was higher in enamel treated with fluoride-free bleaching agent with an additional CaSP application
Kaur et al., 2015⁶	India	In vitro	Freshly extracted anterior teeth	Group I = 10 Group II = 10	Group I = CPP-ACP Group II = CaSP	Evaluate the effect of CPP-ACP and CaSP on microhardness of bleached enamel	Both CPP-ACP and CaSP increase the microhardness of bleached enamel. CaSP is a better agent for increasing microhardness
Krishan et al., 2015²¹	India	In vitro	Freshly extracted sound central incisors	Group I = 10 Group II = 10	Group I = CPP-ACP Group II = CaSP	Evaluate the effect of CPP-ACP and CaSP on the bleached enamel surface for its microhardness	CaSP application provides more remineralization than CPP-ACP
Kshirsagar et al., 2015¹⁴	India	In vitro	Non-carious extracted posterior teeth	Group I = 10 Group II = 10 Group III = 10 Group IV = 10 Group V = 05 Group VI = 05	Group I = CPP-ACP Group II = CaSP Group III = CPP-ACP followed by laser Group IV = CaSP followed by laser Group V = Not demineralized, only dentin exposed Group VI = Not remineralized, not laser treated	Evaluating remineralization and bond strengths of remineralizing agents with or without laser	Higher bond strength of remineralization with CaSP with laser compared to CPP-ACP with/without laser
Raghu et al., 2016²²	India	In vitro	Non-carious premolars	20	CaSP	Evaluate the remineralizing potential of CaSP	CaSP application increases the surface smoothness after 2 weeks of application
Rani et al., 2016²³	India	In vitro	Human permanent mandibular molars	Group A = 10 Group B = 10 Group C = 10	Group A = Control Group B = CPP-ACP cream Group C = CaSP paste	Evaluate the remineralizing potential of CaSP and CPP-ACP	The CaSP paste was effective in remineralizing early enamel lesions than CPP-ACP
Rathi et al., 2017⁷	India	In vitro	Non-carious anterior deciduous teeth	Group I = 10 Group II = 10	Group I = Nano-hydroxyapatite preparation Group II = CaSP	Evaluate the remineralizing efficacy of nano-hydroxyapatite preparation and CaSP	Rathi et al. also found a significant increase in mean microhardness after CaSP application from baseline to Day 7
Sargod et al., 2015²⁵	India	In vitro	Human mandibular premolars	20	CaSP	Evaluate the remineralizing potential of CaSP	Twice a day CaSP application reduces the enamel depth lesion
Thomas et al., 2015²⁴	India	In vitro	Anterior teeth	Group I = 10 Group II = 10 Group III = 10	Group I = CPP-ACP Group II = CaSP Group III = Calcium sodium phosphosilicate	Evaluate the surface microhardness of enamel after the application of three different remineralizing agent	CaSP containing dentifrices gave higher microhardness values compared to CPP-ACP and calcium sodium phosphosilicate

CASP: Calcium sucrose phosphate; CPP-ACP: Casein phosphopeptide-amorphous calcium phosphate; CPP-ACPF: Casein phosphopeptide-amorphous calcium phosphate with fluoride; SnF2: Stannous fluoride.

Supplementary Table 1

PRISMA 2009 Checklist

Section/Topic	#	Checklist Item	Reported on Page#
TITLE
Title	1	Identify the report as a systematic review, meta-analysis, or both.	1
ABSTRACT
Structured summary	2	Provide a structured summary including, as applicable, background; objectives; data sources; study eligibility criteria, participants, and interventions; study appraisal and synthesis methods; results; limitations; conclusions and implications of key findings; systematic review registration number.	1
INTRODUCTION
Rationale	3	Describe the rationale for the review in the context of what is already known.	2
Objectives	4	Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS).	2,3
METHODS
Protocol and registration	5	Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number.	NA
Eligibility criteria	6	Specify study characteristics (e.g., PICOS and length of follow-up) and report characteristics (e.g., years considered, language and publication status) used as criteria for eligibility, giving rationale.	3
Information sources	7	Describe all information sources (e.g., databases with dates of coverage and contact with study authors to identify additional studies) in the search and date last searched.	3
Search	8	Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.	3
Study selection	9	State the process for selecting studies (i.e., screening, eligibility, included in systematic review and, if applicable, included in the meta-analysis).	3
Data collection process	10	Describe method of data extraction from reports (e.g., piloted forms, independently and in duplicate) and any processes for obtaining and confirming data from investigators.	4
Data items	11	List and define all variables for which data were sought (e.g., PICOS and funding sources) and any assumptions and simplifications made.	4
Risk of bias in individual studies	12	Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis.	4
Summary measures	13	State the principal summary measures (e.g., risk ratio and difference in means).	4
Synthesis of results	14	Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I²) for each meta-analysis.	4
Risk of bias across studies	15	Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias and selective reporting within studies).	4
Additional analyses	16	Describe methods of additional analyses (e.g., sensitivity or subgroup analyses and meta-regression), if done, indicating which were pre-specified.	NA
RESULTS
Study selection	17	Give numbers of studies screened, assessed for eligibility and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.	4
Study characteristics	18	For each study, present characteristics for which data were extracted (e.g., study size, PICOS and follow-up period) and provide the citations.	5
Risk of bias within studies	19	Present data on risk of bias of each study and, if available, any outcome-level assessment (see Item 12).	5
Results of individual studies	20	For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group; (b) effect estimates and confidence intervals, ideally with a forest plot.	5,6
Synthesis of results	21	Present results of each meta-analysis done, including confidence intervals and measures of consistency.	5,6
Risk of bias across studies	22	Present results of any assessment of risk of bias across studies (see Item 15).	5
Additional analysis	23	Give results of additional analyses, if done (e.g., sensitivity or subgroup analyses, meta-regression [see Item 16]).	NA
DISCUSSION
Summary of evidence	24	Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users and policy makers).	7
Limitations	25	Discuss limitations at study and outcome level (e.g., risk of bias) and at review level (e.g., incomplete retrieval of identified research and reporting bias).	8
Conclusions	26	Provide a general interpretation of the results in the context of other evidence and implications for future research.	8
FUNDING
Funding	27	Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review.	8

Source: Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 Statement. Syst Rev. 2015;4:1.

Data Sources and Search Strategy

The PubMed, Cochrane Central, and Google Scholar databases were searched from inception until 15th March 2018 in order to retrieve suitable articles. Medical Subject Heading (MeSH) term combinations related to (calcium sucrose phosphate OR CaSP OR ToothMin) AND (remineralizing OR anticay OR anticaries) were used to search the literature for the purpose of this systematic review. The detailed search string is provided in Supplementary Table 2. The search results were restricted to English language only. In addition, bibliographies of retrieved articles were also hand searched to get additional articles.

Table 2.

Risk of Bias Assessment Among Included Studies

Author (Year)	Teeth Randomization	Teeth Free of Caries or Restoration	Adherence to Manufacture’s Instructions for the Usage of Remineralizing Agent	Teeth with Similar Dimensions	Treating Agent Applied by the Same Investigator	Sample Size Calculation	Blinding of the Investigator Applied Remineralizing Agent	Study Quality
Aggarwal et al., 2016⁹	No	Yes	Yes	No	No	No	No	Low
Besten et al., 1995²⁶	No	No	No	No	No	No	No	Low
Gade et al., 2016¹⁹	Yes	Yes	Yes	No	No	No	No	Low
Gangrade et al., 2016²⁰	Yes	No	Yes	No	No	No	No	Low
George et al., 2015¹²	No	Yes	Yes	Yes	No	No	No	Low
Kaur et al., 2015⁶	Yes	Yes	Yes	Yes	No	No	No	Medium
Krishan et al., 2015²¹	No	Yes	No	No	No	No	No	Low
Kshirsagar et al., 2015¹⁴	No	Yes	Yes	No	No	No	No	Low
Raghu et al., 2016²²	Yes	Yes	Yes	No	No	No	No	Low
Rani et al., 2016²³	Yes	Yes	Yes	No	No	No	No	Low
Rathi et al., 2017⁷	No	Yes	No	No	No	No	No	Low
Sargod et al., 2015²⁵	No	Yes	Yes	Yes	No	No	No	Low
Thomas et al., 2015²⁴	No	Yes	Yes	Yes	No	No	No	Low

Supplementary Table 2

Electronic Database Searches (PubMed [Inception-2018.03.15]; Google Scholar [Inception-2018.03.15]; Cochrane Central [Inception-2018.03.15])

1. Calcium sucrose phosphate

2. Calcium sucrose phosphonate

3. CaSP

4. SP (sucrose phosphate)

5. ToothMin

6. Enafix

7. 1-6/OR

8. Remineralizing

9. Remineralization

10. Demineralization

11. Demineralizing

12. Anticaries

13. Anticay

14. 9-13/OR

15. AND/7, 14

Study Selection

We have included studies which had evaluated the following parameters: (a) remineralizing efficacy of CaSP either alone or in comparison with other agents; (b) microhardness of enamel after CaSP application; and (c) arrest of white spot lesion(s).

Reviews, commentaries, letters to the editor, study protocols, and editorials were excluded. Studies with incomplete information, insufficient data, or evaluating properties other than remineralizing efficacy or assessing the remineralizing efficacy of agents other than CaSP were excluded. Two reviewers independently assessed the suitability of articles before inclusion in this systematic review. In case of any differences of opinion pertaining to the inclusion of articles, the first step was to resolve the differences by discussion and reaching a consensus. If a consensus was not reached, then an arbitrator was consulted for a final decision.

Data Extraction and Quality Assessment

Common parameters were compiled in a pre-designed data table from selected literature for further assessment. The parameters included study author, country, type of study, number of teeth per group, remineralizing agents used, and the primary outcomes (Table 1).

Selected literature were assessed for quality using the risk of bias (RoB) tool as described in earlier published studies.^{16, 17} Quality of each included article was assessed by calculating a total score based on the presence (or absence) of the following parameters: randomization of teeth, restoration or use of caries-free teeth, adherence to manufacture’s instructions for the usage of remineralizing agent, similar dimensions teeth, treating agent applied by the same investigator, sample size calculation, and blinding of the investigator applying remineralizing agent. Presence of each of the aforementioned parameter would earn a “Yes”, while the absence would earn a “No” for every article being assessed. Articles having six to seven “Yes” (i.e., total score for article) were considered having a high quality, those having four to five “Yes” were considered to have a medium quality, while those with less than or equal to three “Yes” were considered to have a low quality. Two independent reviewers independently assessed the quality of all the included articles.

Outcome Measures and Statistical Analyses

The primary outcome of this study was to assess the remineralizing efficacy of CaSP by determining the change in microhardness of enamel after CaSP application. The secondary outcome was to assess the potential of CaSP in arresting white spot lesion(s) on the enamel. The articles included in this systematic review were not eligible for meta-analysis due to heterogeneity amongst them. So, only qualitative analysis was done and described in the form of qualitative synthesis.¹⁸

Results

Search Output

The search strategy identified 2,876 articles after running the pre-specified MeSH terms in different databases. Two independent reviewers assessed the suitability of the articles for inclusion in the study based on screening of the title and abstract in the “first pass”. A total of 2,597 articles were excluded on the basis of title and abstract. The articles selected in the “first pass” were further assessed by conducting a full-text review in the “second pass (n = 34)”. Finally, 13 articles were selected for inclusion in this systematic review. Figure 1 shows the study selection process in detail.

Study Description

All the studies were conducted in India^{6, 7, 9, 12, 14, 19-25} except one study by Besten and Giambre,²⁶ which was conducted in the United States. The studies were published between 1995 and 2017 and were in vitro in nature.^{6, 7, 9, 12, 14, 19-26} Majority of the studies compared the remineralizing potential of CaSP with CPP-ACP. The minimum number of teeth used in any group for comparing the remineralizing potential was four. Microhardness was considered as an important parameter for evaluating the remineralizing potential of CaSP and its comparator in 10 of 13 studies.^{6 7 12, 14, 19-24} Majority of the studies^{6, 7, 12, 14, 19-22} assessed the remineralizing potential of CaSP versus its comparator after 7 days of remineralizing agent application, while four studies reported the remineralizing potential of CaSP at 12, 14, 15, and 21 days.^21-24

Figure 1.

PRISMA Flow Diagram Showing Study Selection Process

Table 3.

Microhardness Assessment Summary After Remineralization

Author (Year)	Assessment of Microhardness	Treatment Period	Calcium Sucrose Phosphate		Comparator
Author (Year)	Assessment of Microhardness	Treatment Period	Baseline (Mean ± SD)	After Remineralization(Mean ± SD)	Baseline (Mean ± SD)	After Remineralization(Mean ± SD)
Gade et al., 2016¹⁹	Vickers microhardness test	7 days	NR	234.24 ± 19.05 MPa	NR	213.91 ± 31.81 MPa
Gangrade et al., 2016¹⁹	Vickers microhardness test	7 days	NR	234.24 ± 19.05 MPa	NR	213.91 ± 31.81 MPa
George et al., 2015¹²	Vickers hardness test 200 g load	7 days	NR	322.05 ± 4.66 HV	NR	321.99 ± 8.91 HV
Kaur et al., 2015⁶	Vickers microhardness test 100 g load	7 days	298.2 ± 25.18 HV	306.1 ± 20.46 HV	301.45 ± 39.74 HV	301.26 ± 43.01 HV
Krishan et al., 2015²¹	Vickers microhardness test 100 g load	7 days and 14 days	304.40 ± 39.40 HV	295.73 ± 39.19 HV (7 days)297.41 ± 38.1 HV (14 days)	310.31 ± 36.26 HV	308.83 ± 35.88 HV (7 days)309.66 ± 34.34 HV (14 days)
Kshirsagar et al.,2015¹⁴	Microhardness test 50 g load	7 days	23.71 ± 3.96 HV*25.18 ± 5.02 HV (CaSP with laser)	83.08 ± 7.95 HV103.52 ± 12.63 HV	22.82 ± 6.43 HV26.53 ± 5.48 HV (CPP-ACP with Laser)	81.05 ± 10.72 HV93.50 ± 12.79 HV
Raghu et al., 2016²²	NR	7, 14, and 21 days	357.9 ± 31.2 HV	NR	NR	NR
Rani et al., 2016²³	Vickers microhardness test 100 g load	12 days	317 ± 24.8 HV	210.8 ± 13.5 HV (6th days)255.6 ± 11.6 HV (12th days)	327.73 ± 22.3 MPa	199.83 ± 7.61 HV (6th days)229.36 ± 38.04 HV (12th days)
Rathi et al., 2017⁷	Vickers microhardness testing 100 g load	7 days	197.79 ± 3.11 HV	200.89 ± 3.34 HV	198.17 ± 4.87 HV	206.90 ± 6.8 HV
Thomas et al., 2015²⁴	Vickers microhardness test 50 g load	15 days	183.24 ± 32.26 HV	165.21 ± 72.82 HV	183.14 ± 35.92 HV	160.21 ± 68.73 HV

Note: HV: Hardness value; NR: Not reported. *Represents demineralization.

Quality Assessment

Concerning the quality assessment, none of the studies reported about sample size calculation or blinding of the investigator applying remineralizing agent. Low RoB was observed in the following items: caries-free teeth or restoration, and adherence to the material usage as instructed by the manufacturer (Table 2).

Outcomes

Microhardness Assessment

A total of 10 studies reported the impact on microhardness of enamel after CaSP application (Table 3). Gade et al.¹⁹ reported a higher mean change in the microhardness of enamel following CaSP application, compared with CPP-ACP with fluoride (CPP-ACPF) (between-group difference: 20.33; P = 0.42) and control group (between-group difference: 48.11; P = 0.001). Gangrade et al.²⁰ compared the remineralizing efficacy of CaSP with CPP-ACPF and suggested a higher mean microhardness of enamel following CaSP application (234.24 ± 19.05 MPa vs. 213.91 ± 31.81 MPa; P > 0.05). However, this difference did not reach statistical significance. George et al.¹² studied the microhardness of enamel with and without fluoride-containing bleaching agent and observed a higher mean microhardness in enamel treated with fluoride-free bleaching agent with an additional CaSP application (322.05 ± 4.66 hardness value [HV] vs. 310.70 ± 1.16 HV).

The CaSP was found to be superior to CPP-ACP in increasing the mean microhardness of bleached enamel (306.1 ± 20.46 HV vs. 30.1.26 ± 43.01 HV; P < 0.01).⁶ The percentage increase in microhardness of enamel was higher in CaSP-treated group as compared to CPP-ACP-treated group (6.34% vs. 3.27%). Krishan et al.²¹ reported a highly significant increase in the microhardness of enamel after the first (2.87%) and second (2.27%) cycle of remineralization following CaSP administration (P < 0.001). However, the increase was observed only after the first cycle of remineralization with CPP-ACP (P < 0.05).

In an in vitro study, Kshirsagar et al.¹⁴ found a significant difference in microhardness after 7 days of remineralization in CPP-ACP, CaSP, CPP-ACP with laser and CaSP with laser groups (P < 0.05). The remineralization effect was higher when enamel was treated with CaSP with laser compared to CPP-ACP with laser (311.17% vs. 255.42%). The topical application of CaSP tooth cream twice daily for 2 weeks increased the surface smoothness from 2.32 ± 0.09 (when demineralized) to 2.44 ± 0.20 at 21 days of remineralization, as reported by Raghu et al.,²² The authors further concluded that CaSP has a potential to increase the surface microhardness of enamel even after 14 days of brushing.²²

Rani et al.²³ and Thomas et al.²⁴ demonstrated the superiority of CaSP in increasing the mean surface hardness as compared to CPP-ACP at 12th and 15th day of remineralization. Likewise, Rathi et al.⁷ also showed increase in mean microhardness of enamel after CaSP application.

Arresting White Spot Lesion(s) and Restoring of Enamel Colour

Three studies^{9, 25, 26} assessed the efficiency of CaSP in arresting the white spot lesion(s) on enamel. Besten and Giambre²⁶ found a significant impact of CaSP paste (either alone or in combination with sodium hypochlorite) in changing the colour of fluorotic enamel to that of normal enamel based on the L* values of fluorotic enamel (L* value is an indicator for the color gradient from white to black). The results reported a decrease in L* values of fluorotic enamel from 79.1 ± 6.6 (pre-treatment) to 72.8 ± 2.7 after CaSP paste application. Similar results were observed when CaSP paste in combination with sodium hypochlorite was used (81.4 ± 4.0 pre-treatment to 70.6 ± 3.40 post-treatment). Moreover, the beneficial effect of CaSP application in restoring the colour of white spot lesion(s) to that of normal enamel was also demonstrated.

In another study, Aggarwal et al.⁹ evaluated the protective potential of CaSP as compared to calcium sodium phosphosilicate in controlling the lesion depth. The study revealed that the enamel surface treated with CaSP paste exhibited least lesion depths than the comparator (21.88 µm vs. 35 µm) group.⁹ Sargod et al.²⁵ also found a significant reduction in enamel depth lesion (demineralized: 147.52 ± 11.50 to remineralized: 141.80 ± 13.50) with CaSP application while evaluating its potential on artificial carious lesions.

Discussion

The present systematic review is based on 13 studies assessing the efficacy of CaSP as a remineralizing agent. The results showed a significant improvement in the mean microhardness of enamel post-application of CaSP, compared to CPP-ACP, CPP-ACPF and other remineralizing agents. An increase in the mean microhardness of enamel was evident in all the studies, post-application of CaSP.^{6, 7, 12, 14, 19-24} In addition, CaSP was also found to be effective in restoring the color of white spot lesion(s) and fluorotic enamel to that of normal enamel.²⁶ CaSP was also proven to be superior to other remineralizing agents in controlling the lesion depth.^{9, 25}

The CaSP is a white, non-hygroscopic powder with a bland, neutral taste and high water solubility.^{2, 27} The mechanism by which anticay acts as a cariostatic agent is explained in three pathways: (a) it reduces the rate of demineralization of enamel and increases the rate of remineralization by common ion effect, (b) the sucrose phosphate anion adsorbs directly onto the enamel surface, thereby further inhibiting the process of demineralization, and (c) it actively neutralizes plaque acids.^{13, 27} The remineralization potential is generally determined by the mean change in microhardness of the enamel and restoration of enamel color to that of normal on application of a remineralizing agent.²² Besten and Giambre (in 1995) reported that treatment of enamel with 5.25% sodium hypochlorite, followed by CaSP application, and subsequent placement in artificial saliva was effective in returning both white-spot and fluorotic lesions to a normal color.²⁶ Various studies have reported the pivotal role of CaSP in accelerating the dental enamel remineralization process. In 2016, Raghu et al. reported that twice daily usage (for 14 days) of tooth cream containing CaSP as the main ingredient resulted in an improvement in the surface smoothness.²² Kaur et al. also found an increase in enamel remineralization after CaSP application and cited high water solubility of CaSP as the primary reason for its remineralization potential, owing to the increased release of free calcium and phosphate ions in comparison to saliva.⁶ The remineralization potential of CaSP in terms of significant increase in microhardness after 7 days of use was reported by Kshirsagar et al.¹⁴ CaSP was also found to be a superior remineralizing agent than CPP-ACP in increasing the surface microhardness.²³ CaSP was also found to have plaque-reducing ability.²⁸

The result of systematic review was in corroboration with the findings of published in vitro studies, which evaluated the remineralizing potential of CaSP and had reported a significant improvement in enamel remineralization after CaSP application. The present review has few strengths and limitations. The strengths being that an exhaustive literature search was done in major databases in addition to hand searching of relevant articles. Second, we have included all the data related to primary outcome and have an unbiased quality assessment using the appropriate tool. The limitations of the study were that all the included studies were in vitro in nature. Also, majority of the studies were conducted in India. The study protocol was not registered in any database. Further, we express our inability to search the grey-literature, and the search was restricted to English language only.

Conclusion

This systematic review suggests that CaSP is an effective remineralizing agent compared to others, such as CPP-ACP and CPP-ACPF, in terms of increasing the mean microhardness of enamel and arresting white spot lesion(s). However, to make the evidence more robust and to generalize the findings, there is a need for well-designed randomized controlled trials, assessing the remineralizing potential of CaSP in vivo conditions.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Funding

Writing support was provided by GCE Solutions through academic funding from Abbott Healthcare Pvt Ltd.

References

Oral Health in America: A Report of the Surgeon General (Executive Summary). Website http://www.nidcr.nih.gov/research/data-statistics/surgeon-general, www.nidcr.nih.gov/research/data-statistics/surgeon-general. Accessed April 13, 2018.

Anticay: A Dental Caries Inhibitor—A Review of Research . The Colonial Sugar Refining Company Limited.

Kahar

Harvey

Tisone

Khanna

Prevalence of dental caries, patterns of oral hygiene behaviors, and daily habits in rural central India: a cross-sectional study. J Indian Assoc Public Health Dent . 2016; 14:389-396.

Marcenes

Kassebaum

Bernabé

Global burden of oral conditions in 1990-2010: a systematic analysis. J Dent Res . 2013; 92:592-597.

Bali

Mathur

Talwar

Chanana

Ramesh

Jain

National Oral Health Survey and Fluoride Mapping 2002-2003, Rajasthan . New Delhi: Dental Council of India; 2004:104-106.

Kaur

Sanap

Aggarwal

Kumar

Comparative evaluation of two different remineralizing agents on the microhardness of bleached enamel surface: results of an in vitro study. Indian J Dent Res . 2015; 26:176-179.

Rathi

Baid

Baliga

Thosar

Comparative evaluation of nano-hydroxyapatite preparation and calcium sucrose phosphate on microhardness of deciduous teeth after iron drop exposure: an in-vitro study. J Clin Exp Dent . 2017;9:e579-e583.

Joshi

Nayak

Kuttappa

Menezes

Marure

Sawant

Clinical evaluation of enamel demineralization during orthodontic treatment: an in vivo study using GC tooth mousse plus. J Indian Orthod Soc . 2014; 48:233-238.

Aggarwal

Gupta

Singh

Bindra

SPS.

Comparative evaluation of protective potential of toothmin and novamin containing toothpastes on enamel surface under confocal microscope: an in vitro study. DJAS . 2016; 4:1-4.

10.

Lopatiene

Borisovaite

Lapenaite

Prevention and treatment of white spot lesions during and after treatment with fixed orthodontic appliances: a systematic literature review. J Oral Maxillofac Res . 2016;7:e1.

11.

Bansal

Balhara

Marwaha

Remineralizing efficacy of calcarea fluorica tablets on the artificial carious enamel lesions using scanning electron microscope and surface microhardness testing: in vivo study. Indian J Dent Res . 2014; 25:777-782.

12.

George

Baby

Dhanapal

Charlie

Joseph

Varghese

AA.

Evaluation and comparison of the microhardness of enamel after bleaching with fluoride free and fluoride containing carbamide peroxide bleaching agents and post bleaching anticay application: an in vitro study. Contemp Clin Dent . 2015;6:S163-S166.

13.

Rogerson

The role of a calcium sucrose phosphate-calcium orthophosphate complex* in the reduction of dental caries. Aust Dent J . 1973; 18:160-166.

14.

Kshirsagar

Aggarwal

Gupta

Mukhtar

Comparative assessment of bond strengths of affected dentin, using two different remineralizing solutions with or without lasers: results of an in vitro pilot study. SRM J Res Dent Sci . 2015; 6:82-86.

15.

Moher

Shamseer

Clarke

Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev . 2015;4:1.

16.

Rosa

Piva

Silva

AF.

Bond strength of universal adhesives: a systematic review and meta-analysis. J Dent . 2015; 43:765-776.

17.

Sarkis-Onofre

Skupien

Cenci

Moraes

Pereira-Cenci

The role of resin cement on bond strength of glass-fiber posts luted into root canals: a systematic review and meta-analysis of in vitro studies. Oper Dent . 2014; 39:E31-44.

18.

Popay

Roberts

Sowden

Guidance on the conduct of narrative synthesis in systematic reviews: a product from the ESRC methods programme. Version 1 . 2006;1:b92.

19.

Gade

Comparative evaluation of remineralization efficacy of GC tooth mousse plus and enafix on artificially demineralized enamel surface: an in vitro study. Indian J Oral Health Res . 2016; 2:67-71.

20.

Gangrade

Gade

Patil

Gade

Chandhok

Thakur

In vitro evaluation of remineralization efficacy of different calcium- and fluoride-based delivery systems on artificially demineralized enamel surface. J Conserv Dent . 2016; 19:328-331.

21.

Krishan

Aggarwal

Luthra

Comparative effect of different remineralizing agents on the microhardness of bleached enamel: an in vitro study. JAMDSR . 2015; 3:S66-72.

22.

Raghu

Ananthakrishna

Remineralization potential of calcium sucrose phosphate on demineralized enamel: results of an in vitro study. J Int Oral Health . 2016; 8:704-708.

23.

Rani

Manjula

Reddy

VinayKumar

Mohan

Sowmya

Evaluation of remineralizing potential of calcium sucrose phosphate and CPP-ACP: an in vitro study. Pediatr Dent J . 2016; 26:95-102.

24.

Thomas

Acharya

SR.

Comparative evaluation of the surface microhardness of demineralized enamel after the application of three remineralizing dentrifices: an in-vitro study research. Indian J Appl Res . 2015; 5:108-110.

25.

Sargod

Bhat

Hegde

Karunakaran

Remineralization potential using calcium sucrose phosphate (enafix) on artificial carious lesion: a polaroid microscopic study. Indian J Appl Res . 2015; 5:421-423.

26.

Pamela Den Besten

Giambro

MN.

Treatment of fluorosed and white-spot human enamel with calcium sucrose phosphate in vitro. Pediatr Dent . 1995; 17:340-345.

27.

Craig

The use of a calcium sucrose phosphates-calcium orthophosphate complex as a cariostatic agent. Br Dent J . 1975;138:2528.

28.

Menon

Varma

Kumaran

Xavier

Govinda

Kumar

JS.

Efficacy of a calcium sucrose phosphate based toothpaste in elevating the level of calcium, phosphate ions in saliva and reducing plaque: a clinical trial. Contemp Clin Dent . 2018; 9:151-157.

Evaluation of Remineralizing Efficacy of Calcium Sucrose Phosphate: A Systematic Review of In Vitro Studies

Abstract

Abstract

Keywords

Introduction

Methods

Characteristics of Included Studies

PRISMA 2009 Checklist

Data Sources and Search Strategy

Risk of Bias Assessment Among Included Studies

Electronic Database Searches (PubMed [Inception-2018.03.15]; Google Scholar [Inception-2018.03.15]; Cochrane Central [Inception-2018.03.15])

Study Selection

Data Extraction and Quality Assessment

Outcome Measures and Statistical Analyses

Results

Search Output

Study Description

PRISMA Flow Diagram Showing Study Selection Process

Microhardness Assessment Summary After Remineralization

Quality Assessment

Outcomes

Microhardness Assessment

Arresting White Spot Lesion(s) and Restoring of Enamel Colour

Discussion

Conclusion

Footnotes

Declaration of Conflicting Interests

Funding

References