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. 2024 Jun 14;10(1):16–23. doi: 10.1177/23800844241252816

Enhancing Intraoral Fluoride Retention in Older Adults: A Randomized Crossover Study

J Baez-Polan 1, TE Danciu 2, D Sweier 3, C González-Cabezas 3, M Fontana 3, LMA Tenuta 3,✉
PMCID: PMC11653333  PMID: 38877716

Abstract

Introduction:

Previous studies have shown that a calcium prerinse can increase intraoral fluoride retention from a fluoride rinse. To explore the potential of this approach to control root caries, we assessed intraoral fluoride bioavailability after a calcium prerinse in older adults with normal to low salivary flow rates.

Methods:

In a 2-period crossover trial (NCT04239872), 20 participants (65–80 y old), with low or normal salivary flow rate, rinsed for 1 min with a 0.05% NaF mouth rinse (226 ppm F, F only) or with this rinse immediately after a 1-min rinse with 150 mM calcium lactate (Ca→F). Dental biofilm and saliva samples were collected before and up to 2 h after the rinse(s). Fluoride concentrations in saliva (whole and clarified) and dental biofilm (fluid and solid phases) were blindly determined. Data were statistically analyzed by a mixed-effects model for the effect of treatment, time, and their interaction (α = 5%).

Results:

The Ca→F group resulted in significantly higher fluoride concentrations in all variables analyzed, for almost all of the collection time points. The effect was greater in the biofilm solids and whole saliva (compatible with the formation of calcium fluoride deposits) and still significant (P < 0.001) after 2 h in the biofilm fluid and clarified saliva, suggesting that fluoride stored in insoluble particles was released, increasing free fluoride.

Conclusion:

The use of a calcium prerinse before a fluoride rinse was able to prolong intraoral fluoride bioavailability in older adults.

Knowledge Transfer Statement:

A calcium prerinse increased intraoral fluoride bioavailability in older individuals. This approach could be used to improve root caries control without the need to increase the fluoride concentration in dental products.

Keywords: calcium, root caries, dental care for aged, mouthwashes, toothpastes, xerostomia

Introduction

The widespread use of fluoride has been the cornerstone of caries control. Fluoride interferes with tooth mineral balance, reducing mineral loss when available at very low concentrations in the oral fluids (i.e., saliva, fluid of dental biofilm). Therefore, fluoride availability in these fluids has been used as an indicator of anticaries potential in many different studies (Tenuta and Cury 2013).

The daily use of fluoride toothpastes and rinses is expected to keep dental caries under control by increases of intraoral fluoride levels throughout the day. However, in more vulnerable individuals, with increased risk factors, such as older adults with medication-induced hyposalivation, new or existing caries lesions can progress under the use of available over-the-counter fluoride products (Paris et al. 2020). Increasing the intraoral availability of fluoride via the use of high-fluoride, prescription toothpastes seems like the best alternative for these individuals (Meyer-Lueckel et al. 2019). It has also been shown in a preclinical model that the use of twice/day over-the-counter fluoride mouth rinse can help control mineral loss in patients with radiation-induced hyposalivation (Meyerowitz et al. 1991). Nevertheless, the ability of these supplementary fluoride products to maintain elevated intraoral fluoride concentrations is limited by the restricted number of positively charged intraoral binding sites where fluoride could be retained for later release (Rose et al. 1996; Vogel 2011). This is a limitation of most oral care products; without a prolonged intraoral retention by binding to positively charged ions (such as calcium), or the formation of calcium fluoride as a longer-term fluoride reservoir (Vogel 2011; Vogel et al. 2014), most of the fluoride used for brushing/mouth rinsing is rapidly lost: for example, 2 h after brushing with over-the-counter fluoride toothpastes and/or rinses (226–1,500 ppm F), fluoride concentrations usually lower than 0.1 ppm F (0.005 mmol/L) are observed in saliva (Zero et al. 1988; Duckworth and Morgan 1991). In the biofilm fluid, fluoride concentrations around 0.5 ppm F (0.026 mmol/L) or less are observed 1 h after a 226-ppm F mouth rinse (Vogel, Schumacher, et al. 2008; Vogel et al. 2010).

Yet, intraoral fluoride retention can be improved if a calcium treatment is used before a fluoride treatment. Previous studies with younger adults showed that a calcium prerinse, used before a fluoride rinse, is able to significantly increase saliva and biofilm fluoride concentrations for hours (Vogel, Chow, et al. 2006; Vogel, Chow, et al. 2008; Vogel, Schumacher, et al. 2008; Vogel et al. 2014). This strategy was as effective as a 4 times higher fluoride treatment in inhibiting enamel mineral loss in an in situ caries study (Souza et al. 2016). Here we tested the potential of this approach to enhance intraoral fluoride retention in older adults with normal to low salivary flow rates.

Methods

Trial Design

In this randomized crossover trial (2 experimental periods), participants (n = 20, 65 y or older) with salivary flow rates from normal to hyposalivation were randomly allocated to start the experiment at 1 of the 2 treatments being investigated: 0.05% NaF rinse (226 ppm F) (“F-only” group) or the same rinse preceded by a 150-mM calcium lactate rinse (“Ca→F” group). The other treatment was tested in the second experimental period. These experimental groups were chosen to allow the comparison of an established method of individual fluoride use (over-the-counter fluoride rinse) versus its use after a calcium prerinse. Biofilm and saliva samples were collected before and up to 2 h after the rinses. Per protocol, fluoride concentrations in the biofilm fluid and solid phases were considered the primary outcomes. Fluoride concentration in saliva and calcium concentration in the biofilm and saliva were secondary outcomes (calcium analysis and results are described in Appendix 6). Washout periods of at least 4 d (Fernández et al. 2015) were allowed between periods. Carryover effect was investigated using baseline fluoride levels in biofilm and saliva in participants allocated to the 2 different sequences (Appendix 4). Results were analyzed using a mixed-effects model for the comparison of treatments and time points for each variable. Also, the area under the curve of fluoride concentration versus time was calculated for the biofilm and saliva variables, as well as compared between groups using a paired t test.

Ethical Aspects, Participants’ Recruitment, Enrollment, and Randomization

Prior to enrollment, the study was approved by the University of Michigan IRBMED and registered in ClinicalTrials.gov (NCT04239872), where the study protocol can be found as a pdf file (Tenuta 2020). All participants signed an informed consent before being considered for the study. They were older adults (65 y or more), recruited from the clinics of the University of Michigan School of Dentistry and from a University of Michigan volunteer registry (https://umhealthresearch.org/). Inclusion criteria included having at least 20 natural or crowned teeth (being at least 4 in each quadrant), no signs of active periodontal disease or urgent dental needs, and good general health. Exclusion criteria included patients with active periodontitis, oral pain, or in need of urgent dental care. The experiment was conducted in Ann Arbor, Michigan, which has fluoridated water supply (0.7 ppm F), but no information was obtained from participants regarding fluoridated water use.

Sample size was calculated based on the data from Souza et al. (2016) of biofilm samples collected approximately 10 h after using similar rinses, with biofilm fluid fluoride concentrations of 73 ± 59 µM F (F group) and 161 ± 100 µM F (Ca→F group). Using these figures and considering an 80% power to detect differences at the 5% significance level, sample size was calculated at 15 per group (twomeans, Stata/SE 15.1 for Mac). The final sample size was increased by 30%, to 20 participants, to account for losses to follow-up.

Recruitment started in March 2020, and the trial was completed in April 2021, after a few months of recruitment/enrollment pause due to the COVID-19 pandemic. To enroll participants with a range of salivary flow rates, in a screening visit, unstimulated (using the drooling method) and stimulated (by chewing of a piece of Parafilm) saliva samples were collected for 5 min each and the volume determined by weight (considering 1 g = 1 mL of saliva). Hyposalivation was defined as unstimulated flow rate <0.1 mL/min and/or stimulated flow rate <0.5 mL/min (Sreebny 2000). Per protocol, half of the participants would have normal salivary flow and half hyposalivation. After having enrolled 10 participants with normal salivary flow but still missing 6 with hyposalivation, recruitment efforts targeted individuals with reported dry mouth. Five additional participants with hyposalivation were enrolled, and at the end of the enrollment period, 1 final participant with normal flow was included, reaching the sample size of 20 (change from protocol) (Fig. 1). Therefore, the final sample consisted of 11 participants with normal salivary flow and 9 with low unstimulated and/or stimulated salivary flow.

Figure 1.

Figure 1.

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Flow diagram of the crossover study. The asterisk (*) identifies a protocol deviation with the inclusion of a participant with normal salivary flow to account for the sample size of 20. §Pseudorandomization (see text for details).

All participants tested both rinse combinations (crossover study). The order in which they tested the rinses was determined using a pseudorandom procedure. First, a computer-generated randomized sequence was created (function “rand”; MS Excel for Mac, v.16.21, Microsoft Corp.) to assign one of the sequences (F only first, then Ca→F, or vice versa) to a list of numbers ranging from 1 to 30. These numbers were allocated to participants as they were screened (considering the possibility of screening more than 20 participants in order to enroll 20). As participants were screened, the identification number received (1, 2, 3, etc.) would indicate the order in which the rinses would be tested according to the previously randomized sequence. In the end, 11 of the participants tested rinses in the sequence F only first, then Ca→F, and the other 9 in the sequence Ca→F first, then F only (Fig. 1).

Rinsing Procedures and Sample Collection

Participants used a standardized fluoride toothpaste (Crest Cavity Protection, 1,100 ppm F [NaF]) and toothbrush for at least 7 d before the experimental periods. They were asked to refrain from using other mouth rinses/oral health products during the study and from drinking green/black tea (fluoride sources) on the night before or the day of the visits. On experimental days, they were asked to not brush their teeth, to allow biofilm buildup for collection.

Visits happened in the morning or afternoon (same period was maintained throughout the study for each participant to avoid variations caused by the circadian rhythm; Dawes 1972) at the Graduate Restorative Clinic of the University of Michigan School of Dentistry. At least 4 d were allowed between the 2 experimental periods (Fernández et al. 2015). Participants were asked to avoid eating for 1 h prior to the start of their visit.

Rinses were prepared from sodium fluoride and calcium lactate salts, as detailed in Appendix 2. Aliquots of each rinse were transferred to sealed rinse bottles to be opened by the participants during the rinse procedure. Because the participants would use 1 rinse (F only) or 2 rinses (Ca→F), blinding was not possible. Concealment was ensured by having the dentist delivering the rinse(s) and collecting the samples receiving the preassigned rinse(s) only immediately before each visit, when the scheduled participant would also become aware of the treatment being tested.

Rinsing (15 mL of each rinse) was performed for 1 min, with participants seated in a dental chair, with the clinical researcher by their side. This dentist guided the participants through saliva sampling and collected the biofilm samples. In the Ca→F group, immediately after expectorating the first rinse, the participant repeated the 1-min procedure with the second rinse. A timer was started at the final spit, to time the collection of subsequent saliva and biofilm samples.

Biofilm samples were collected from 1 quadrant of the mouth at each time point (baseline and 15, 60, and 120 min after the fluoride rinse), except from the lower anterior teeth due to the higher fluoride concentration in this area (Staun Larsen et al. 2017). The order of quadrants was randomized for each participant and kept the same for the 2 treatment groups (Staun Larsen et al. 2017). Using a plastic toothpick, all the biofilm visible on the buccal surfaces of teeth in each quadrant was scraped. The biofilm was immediately immersed in mineral oil to avoid evaporation of the fluid (Tenuta et al. 2006). Each biofilm sampling took about 1 min. Biofilm samples were stored in a cooled rack until transportation to the laboratory for processing, within 1 h of collection.

Unstimulated saliva samples were collected for 5 min, before the rinsing procedures (baseline) and starting at approximately 16*, 30, 61*, 90, and 121* min after the rinse(s) (*immediately after biofilm collections). Participants were seated in the dental chair, with heads tilted forward, without speaking, and were instructed to let the saliva drool into the collection tube. Within 1 h of collection, saliva samples were transferred to the laboratory for processing.

Determination of Fluoride Concentration in Biofilm and Saliva Samples

Details on the analysis of fluoride concentration in the biofilm and saliva can be found in Appendix 3. Briefly, the biofilm fluid was extracted by centrifugation, and the remaining solids were acid-extracted to obtain total fluoride (Cury et al. 1997; Tenuta et al. 2006). The remaining biofilm residue was used to extract total proteins for the estimation of biofilm mass (Dall Agnol et al. 2021). Saliva samples were split into a noncentrifuged sample (whole saliva) and a centrifuged sample (clarified saliva).

Fluoride concentration in all biofilm and saliva pools was determined using a fluoride electrode adapted for microanalysis. Protein concentration was determined using the Lowry method (DC protein assay; Bio-Rad). All analyses were made by analysts blinded to the treatment group, using only participant number, period (1 or 2), and time point as the identifier. Therefore, analysts were not blind to the time point under analysis.

Adverse Events

Adverse events or unanticipated problems were indirectly assessed through the rinsing and sample collections by the dentist.

Statistical Analysis

The absence of carryover effect of treatments used at different sequences was checked by the baseline fluoride levels in biofilm and saliva.

Prism 9 for MacOS (v.9.4.1; GraphPad Software) was used for the statistical analysis (α = 5%). For comparisons of treatments at different time points, a mixed-effects model was used, considering time, treatment, and the interaction between them as fixed-effect factors, and participants as a random-effect factor. The presence of outliers was investigated by the Grubbs method (α = 0.0001). One outlier was identified in the concentration of fluoride in the biofilm fluid (F-only group, 15 min, 7.15 mmol F/L). Analyses of this variable with or without (Appendix 7) the outlier were done. For significant interactions, the effect of treatments within time points, and time points within treatments, was further investigated (Bonferroni). All fluoride data were transformed into the log10 to fit the assumption of normal distribution of errors.

For participants with samples collected at all time points, the area under the curve (AUC) of fluoride concentration versus time was calculated for biofilm and saliva outcomes, and the 2 treatments were compared using the paired t test. All AUC data, except for fluoride in the biofilm fluid, were transformed into the log10 to fit the assumption of normal distribution of errors.

Results

Twenty participants (12 females; 8 males, 70.9 ± 4.6 y old [mean ± SD, range 65–80], 17 non-Hispanic Whites) were enrolled. Participants’ salivary flow rate ranged from 0.003 to 1.12 mL/min for unstimulated saliva and from 0.04 to 3.1 mL/min for stimulated saliva. Details about participant race/ethnicity, salivary flow rate, number of decayed, missing or filled teeth (DMFT) and surfaces (DMFS), number of medications used, and the sequence used can be found in Appendix 1. Nineteen participants completed both experimental periods; 1 was lost to follow-up after completing the first experimental period on treatment Ca→F (Fig. 1). This participant was included in the statistical analysis (intention-to-treat approach). No adverse events or unintended effects were reported.

Enough saliva was collected from almost all participants and time points to be measured using our microtechniques. However, we were unable to collect enough biofilm samples at all of the time points (see Appendix 5 for details).

The absence of carryover effect between treatments was observed by the baseline fluoride values and AUCs for participants enrolled in the 2 different sequences (Appendix 4).

The interaction between factors treatment and time was statistically significant for all fluoride variables analyzed (P < 0.01). The comparison among the treatments at each time point, of relevance for this study, is highlighted in Figure 2 (see Appendix 5 for other comparisons). No significant differences were found among the groups before the rinses, for any of the variables (P > 0.05). After the rinses, the Ca→F group resulted in significantly higher fluoride concentrations when compared with the F-only group for all variables at almost all collection times. The exception was the fluoride concentrations in the biofilm fluid and clarified saliva 15 min after the rinses, when the 2 groups were not significantly different from each other. Importantly, the 2 treatments continued to significantly differ from each other in all variables even 2 h after the rinses.

Figure 2.

Figure 2.

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Fluoride concentration (geometric mean ± 95% CI) in the dental biofilm and saliva according to the treatments and time points, with the calculated area under the curve (AUC) shown on the right (the AUC was calculated only from samples with all time points available). Saliva samples were collected for 5 min, starting immediately after the collection of the biofilm samples (at approximately 16, 30, 61, 90, and 121 min after the rinses); these variations in collection time are not noted in the x-axes for simplification. At each time point, asterisks indicate when the treatment groups differed significantly (*P < 0.005, **P < 0.001). For details about the difference between time points within each group, please refer to Appendix 5. The comparison between the AUCs is shown as the mean of differences between paired data points (± 95% CI), with the P values shown on top.

Statistically significant differences were found for all variables in the AUC of fluoride concentration versus time, except for fluoride in the biofilm fluid (Fig. 2).

Discussion

This study was conducted between 2020 and 2021, under COVID-19 restrictions for seeing patients, especially older adults, in dental clinics. The recruitment of participants with hyposalivation was particularly challenging, with about two-thirds of participants screened for their reported dry mouth (xerostomia) having measured salivary flow in the normal range (Fig. 1). Both factors contributed to our final sample comprising 1 fewer individual with hyposalivation than planned. This emphasizes the disconnect between the subjective symptoms of xerostomia and actual hyposalivation (Thomson et al. 1999).

The results confirm that the use of a calcium treatment before a fluoride rinse can increase intraoral fluoride retention and result in sustained, increased levels of bioavailable (free) fluoride in saliva and the dental biofilm (Vogel, Chow, et al. 2006; Vogel, Shim, et al. 2006; Vogel, Chow, et al. 2008; Vogel, Schumacher, et al. 2008; Vogel et al. 2014). The current study in older adults with a range of salivary flow rates indicates the potential of this approach to affect caries progression in this population by improving intraoral fluoride retention. The increase in fluoride bioavailability by this approach was previously investigated only in clarified saliva samples or at only 1 time point after the rinse(s) (1 h or 12 h) (Vogel, Chow, et al. 2006; Vogel, Shim, et al. 2006; Vogel, Chow, et al. 2008; Vogel, Schumacher, et al. 2008; Vogel et al. 2014). In the present study, the analysis of total and free fluoride concentrations in the biofilm and saliva, for up to 2 h after the rinses, contributes additional information about the mechanism of increased fluoride retention. Also, no adverse events were observed in this study.

The vast difference between the 2 groups in the biofilm solids and whole saliva fluoride concentration (Fig. 2a, c) suggests that most of the fluoride is retained as insoluble particles (e.g., calcium fluoride precipitates) or bound to bacterial cells (Vogel 2011). An increase in calcium concentrations (Appendix 6) is also supportive of the formation of calcium fluoride (although the observed increase in calcium is smaller due to its greater oral concentrations when compared with fluoride). We have previously shown that calcium fluoride precipitates are not formed in the biofilm unless calcium is used prior to a fluoride rinse (Vogel et al. 2010, 2014) and that a significant boost in fluoride concentration in biofilm-like bacterial pellets is only achieved when calcium fluoride is formed (Nóbrega et al. 2019).

The use of calcium prior to a fluoride treatment can also increase the concentration of free, soluble fluoride in the oral fluids (Fig. 2b, d). At 15 min after the fluoride rinse, the groups did not differ in fluoride concentration in the biofilm fluid and clarified saliva, probably because free fluoride provided by the rinse itself is the main source of the ion at that time. However, the elevated fluoride concentration observed subsequently in the Ca→F group indicates that insoluble reservoirs (from biofilm solids and whole saliva) can provide free ions to these fluids. That explains why the use of calcium prior to a fluoride rinse is able to sustain increased free fluoride levels in the saliva and biofilm fluid (Vogel, Chow, et al. 2006; Vogel, Shim, et al. 2006; Vogel, Chow, et al. 2008; Vogel, Schumacher, et al. 2008; Vogel et al. 2014). Notably, 2 h after the rinses, fluoride concentrations were increased roughly 4 and 3.5 times, respectively, in the biofilm fluid and clarified saliva, when a calcium rinse was used before fluoride.

The increased fluoride concentrations declined differently in the biofilm and saliva. In whole saliva, a clear reduction of the fluoride concentration was observed in the Ca→F group over the course of 2 h, whereas in the biofilm solids, these concentrations did not decline over time (Appendix 5). Clearly, any insoluble fluoride is cleared away more quickly from saliva (or other intraoral sites that contribute to salivary fluoride, such as the oral mucosa; Zero et al. 1992; Duckworth 2013; Staun Larsen et al. 2019) than from the biofilm.

The very effective and yet simple approach used in this study has promising implications for caries control in older adults. They may be of an increased risk for root caries, irrespective of salivary flow, because root dentin is more soluble than enamel, and modest pH declines (prompted by low cariogenicity sugars such as starch and lactose) can cause mineral loss (Aires et al. 2002; Aires et al. 2008). Aging also brings changes in diet, access to care, and frailty, resulting in increased caries risk (Walls et al. 2000; Moynihan 2007; Bradbury et al. 2008; Ramsay et al. 2018; Hakeem et al. 2021). The effects observed here with older adults, in addition to other age ranges previously studied (Vogel, Chow, et al. 2006; Vogel, Chow, et al. 2008; Vogel, Schumacher, et al. 2008; Souza et al. 2016), suggest that the anticaries effect of fluoride can be improved by modifications of available therapies, without the need to increase their fluoride concentration. This strategy of fluoride delivery can also affect caries control in other vulnerable groups, such as children or patients under radiotherapy for head and neck cancer. Approaches to use the principles of intraoral fluoride retention explored here in 1 single treatment application have started to be explored, such as fluoride containing nanoparticles targeted to bind to the dental biofilm (Tenuta et al. 2022). Because the anticaries effect of fluoride increases at higher doses (Meyer-Lueckel et al. 2019; Walsh et al. 2019), a prolonged increase in intraoral fluoride ion concentration is desirable. However, before clinical recommendations can be made, the anticaries effect of the strategy tested here has to be confirmed in clinical studies measuring dental caries as the outcome.

Our study has limitations. 1) Participants were allowed to brush their teeth until the day before sampling, and many of them did not have enough biofilm for collection. The fact that we were still able to observe significant differences between groups for the biofilm variables suggests that the difference between them is strong enough to not be jeopardized by a reduced sample size. 2) Some participants had a low salivary flow rate, and in some time points, no saliva could be collected, which may have affected the results. A crossover design was chosen to reduce this potential interference in the study results. 3) We did not use a placebo rinse before the fluoride-only rinse, which could have allowed us to blind participants to the treatments, because we wanted to compare treatments that would be used by patients. Using a placebo before the fluoride rinse could have affected fluoride retention, impairing the comparison to the clinical use. 4) The tested rinses were made from pure chemicals, without any additives, and it is unclear which effect that flavoring and foaming agents (Vogel et al. 2015) could have on the results. 5) We did not acid-extract the whole saliva samples in order to dissolve all insoluble fluoride particles in it (Vogel et al. 2015). However, this should not affect our conclusions; our methodology may have reduced the amount of fluoride recovered in the whole saliva samples in the Ca→F group, and the difference between the 2 groups could be even bigger than what was observed here.

In summary, we showed that the use of a calcium prerinse before a fluoride rinse can improve the bioavailability of free fluoride in the oral fluids of older adults with a range of salivary flow rates. The effect seems associated with the formation of insoluble fluoride reservoirs that can release fluoride ions over time. This approach should be further investigated for its potential to enhance the anticaries effect of fluoride for high-caries risk groups.

Author Contributions

J. Baez-Polan, contributed to data acquisition, critically revised the manuscript; T. Danciu, D. Sweier, C. González-Cabezas, M. Fontana, contributed to data interpretation, critically revised the manuscript, L.M.A. Tenuta, contributed to conception, design, data acquisition, analysis and interpretation, drafted and critically revised the manuscript. All authors have their final approval and agree to be accountable for all aspects of work.

Supplemental Material

sj-pdf-1-jct-10.1177_23800844241252816 – Supplemental material for Enhancing Intraoral Fluoride Retention in Older Adults: A Randomized Crossover Study
sj-pdf-1-jct-10.1177_23800844241252816.pdf (159.4KB, pdf)

Supplemental material, sj-pdf-1-jct-10.1177_23800844241252816 for Enhancing Intraoral Fluoride Retention in Older Adults: A Randomized Crossover Study by J. Baez-Polan, T.E. Danciu, D. Sweier, C. González-Cabezas, M. Fontana and L.M.A. Tenuta in JDR Clinical & Translational Research

sj-pdf-2-jct-10.1177_23800844241252816 – Supplemental material for Enhancing Intraoral Fluoride Retention in Older Adults: A Randomized Crossover Study
sj-pdf-2-jct-10.1177_23800844241252816.pdf (976.2KB, pdf)

Supplemental material, sj-pdf-2-jct-10.1177_23800844241252816 for Enhancing Intraoral Fluoride Retention in Older Adults: A Randomized Crossover Study by J. Baez-Polan, T.E. Danciu, D. Sweier, C. González-Cabezas, M. Fontana and L.M.A. Tenuta in JDR Clinical & Translational Research

Acknowledgments

Ms. Savannah Price is acknowledged for the excellent technical support, and Ms. Taylor Cezon and Emily Yanca are acknowledged for the help with study coordination.

Footnotes

A supplemental appendix to this article is available online.

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

Funding: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by the Michigan Institute for Clinical & Health Research (MICHR), University of Michigan (UL1TR002240), and the University of Michigan Rackham Graduate School Fund for Graduate Students. The funders had no role in the study planning, execution, or interpretation of its results.

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Associated Data

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Supplementary Materials

sj-pdf-1-jct-10.1177_23800844241252816 – Supplemental material for Enhancing Intraoral Fluoride Retention in Older Adults: A Randomized Crossover Study
sj-pdf-1-jct-10.1177_23800844241252816.pdf (159.4KB, pdf)

Supplemental material, sj-pdf-1-jct-10.1177_23800844241252816 for Enhancing Intraoral Fluoride Retention in Older Adults: A Randomized Crossover Study by J. Baez-Polan, T.E. Danciu, D. Sweier, C. González-Cabezas, M. Fontana and L.M.A. Tenuta in JDR Clinical & Translational Research

sj-pdf-2-jct-10.1177_23800844241252816 – Supplemental material for Enhancing Intraoral Fluoride Retention in Older Adults: A Randomized Crossover Study
sj-pdf-2-jct-10.1177_23800844241252816.pdf (976.2KB, pdf)

Supplemental material, sj-pdf-2-jct-10.1177_23800844241252816 for Enhancing Intraoral Fluoride Retention in Older Adults: A Randomized Crossover Study by J. Baez-Polan, T.E. Danciu, D. Sweier, C. González-Cabezas, M. Fontana and L.M.A. Tenuta in JDR Clinical & Translational Research

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