Sodium Monofluorophosphate Research Articles

Treatment of postmenopausal osteoporosis with sodium monofluorophosphate and calcium carbonate

Treatment of postmenopausal osteoporosis with sodium monofluorophosphate and calcium carbonate

Effects of combination therapy with bisphosphonate and sodium monofluorophosphate on bone mass in osteoporosis

Effects of combination therapy with bisphosphonate and sodium monofluorophosphate on bone mass in osteoporosis

Most of resistant cases to sodium fluoride therapy can be made responders by using sodium monofluorophosphate

Most of resistant cases to sodium fluoride therapy can be made responders by using sodium monofluorophosphate

The value of anti-caries and anti-plaque dentifrices at a community level.

Although dentifrices (in a modern sense) were first introduced at the turn of the century, it was not until the advent of fluoride-containing compounds that any of therapeutic value was produced. In the early post-war years, formulation compatibility difficulties occurred, with the result that none was demonstrated to have clinically proven efficacy until stannous fluoride was successfully incorporated in the "Crest" formulation of 1955. Thereafter, sodium monofluorophosphate (SMFP) appeared, to be followed by organic and acid-phosphate fluoride preparations, most of which were shown to produce clinical benefit over placebo controls. Since the late 1970's, however, such studies have been deemed unethical in many countries in view of the almost universal availability of efficacious fluoride dentifrices. While an NaF formulation was the first to be tested (albeit unsuccessfully) by Bibby (1945), there was a considerable time period before the arrival of both stable and effective silica-based systems in the early 1980's. Results of studies have varied, but the largest ever double-blind NaF/SMFP head-to-head dentifrice trial yet published (Stephen et al., 1994) has indicated a 6.4% significant benefit in favor of NaF (in silica) over SMFP. With respect to the effect of dentifrice fluoride levels, above 1000 ppm dose-response caries reductions have been obtained, but the efficacy of preparations containing 500 ppm F or less has yet to be demonstrated. In relation to root caries, Jensen and Kohout (1988) reported a 41.4% DFS significant reduction in subjects who used a NaF/silica dentifrice at 1100 ppm F, over a one-year period.

Monofluorophosphate increases lumbar bone density in osteopenic patients: A double-masked randomized study

To assess the efficacy of combined sodium monofluorophosphate and calcium therapy (FC) in increasing lumbar bone mineral density (BMD) in patients with low bone mass, we conducted a prospective double-masked randomized study in 94 patients aged 50-70 years. Patients were selected on the basis of a lumbar BMD at least 2 standard deviations (SD) below the young adult mean (T-score) but without evidence of previous vertebral fracture (severe osteopenia). They were randomly assigned to receive for 2 years, twice a day, either FC (13.2 mg F-, i.e. 100 mg sodium monofluorophosphate, and 500 mg Ca2+) or C (500 mg Ca2+). Vertebral BMD was measured by dual photon absorptiometry from L2 to L4. Comparison at final assessment in the 76 eligible patients (Student's t-test) showed a statistically significant difference between the two groups in the mean BMD increase in favour of FC. Furthermore, Student's t-test showed a significantly greater increase in lumbar BMD in FC-treated patients at 1 year, at 18 months and after 2 years (mean increase of 7.1%/year). These results were confirmed by ANOVA at 1 year, at 18 months and after 2 years of treatment. Of the FC-treated patients, 71.4% were considered to have responded (i.e. they showed an increase in lumbar BMD of more than 0.034 g/cm2). The dosage of 26.4 mg fluoride ion/day (i.e. 200 mg monofluorophosphate/day) therefore appears to be safe and to increase the BMD effectively in patients with low bone mass prior to vertebral fracture.

The diffusion and enzymic hydrolysis of monofluorophosphate in dental plaque.

Although the ability of dental plaque to hydrolyze sodium monofluorophosphate (MFP) has been known for some time, its effect on the F- concentration at the plaque-enamel interface is undefined. We have determined enzyme kinetic values for MFP hydrolysis and diffusion coefficients so that the penetration and degradation of MFP in plaque can be modeled by computer. The KM and Vmax values for natural human plaque were 1.77 mmol/L and 41.4 nmol/min/mg protein, respectively, at pH 8.0. At pH 6.0, the Vmax was lower, 15.6 nmol/min/mg, but KM was not significantly different. Competitive inhibition by orthophosphate gave a Ki of 4.55 mmol/L. The diffusion coefficient for MFP in artificial plaque was 1.91 x 10(-6) cm2/sec. When these data were used for mathematical modeling of the effects of rinsing with MFP and F- solutions, compared with an equivalent NaF application, the concentration of F- from MFP was lower at the inner surface of plaque, and the peak occurred later. Both pH and plaque thickness had a marked effect on the amount of MFP that could penetrate: At pH 8.0, almost none reached the inner surface of a 1-mm-thick plaque intact. At pH 6.0, however, more MFP was able to penetrate, due to lower MFPase activity. While MFP diffusion is inherently slower than that of F-, enzymic degradation increases the gradient for inward diffusion. If the conventional view that MFP in toothpaste acts as a source of F- is true, then MFP toothpaste should be formulated to optimize MFPase activity in dental plaque.

Treatment of bone in elderly subjects: calcium, vitamin D, fluor, bisphosphonates, calcitonin.

Several approaches may be suggested for prevention or treatment of senile osteoporosis. In elderly patients, an association of calcium and vitamin D supplementation has been shown to reduce nonvertebral fractures up to 40% over an 18-month period. Calcitonin, given parenterally or nasally, may prevent further bone loss and has been reported to significantly decrease vertebral and hip fractures. This hormone also possesses an important analgesic effect. Fluoride salts are the most effective way to significantly increase bone mass, mainly at the trabecular site. The optimal doses and regimens remain to be clearly established. The use of new formulations like sodium monofluorophosphate are likely to facilitate the search of the optimal therapeutic window. Bisphosphonates are potent inhibitors of bone resorption. They have been shown to significantly increase trabecular bone mass without impairment of cortical bone. Their use may be associated with a significant decrease in vertebral fractures, mainly in patients with severe osteoporosis. The new, second and third generation of bisphosphonates (tiludronate, risedronate, alendronate) look extremely promising but their widespread use will only be possible after a confirmation of the absence of a deleterious effect on bone quality (alendronate) and after demonstration of a reduction in vertebral and/or hip fractures following a prolonged use.

Long Term Stability of Sodium Monofluorophosphate

AbstractThis paper reports data on the long term stability of the phosphorus-fluorine bond of sodium monofluorophosphate (MFP). Spontaneous hydrolysis of the drug in bulk form follows first order kinetics. Chemical stability, expressed as its t1/2, was found to differ with different MFP preparations (t1/2 = 35 to 114 months). Chemical stability of MFP in tablets appears dependent upon the method employed in their preparation. The long term stability of aqueous solutions is affected, as expected, by pH and temperature.

A biopharmaceutic approach in designing a controlled release tablet of sodium monofluorophosphate: 1. in vitro and in vivo studies in beagle dogs

The purpose of this study was to develop a controlled release tablet (CRT) of sodium monofluorophosphate (NaMFP) based on biopharmaceutic and pharmacokinetic principles. NaMFP was introduced in the early eighties to treat osteoporosis. The required dose size (200 mg of NaMFP) and time of drug delivery (8.3 h) were theoretically determined based on the pharmacokinetic parameters of fluoride (F-). A CRT was formulated with ethyl cellulose (EC) by the direct compression method. The ratio of drug to polymer was adjusted 1:1, after studying the in vitro release profiles. The release mechanism from the developed dosage form followed the square root of time relationship. This dosage form was evaluated for its in vivo performance in dogs. The pharmacokinetics of F-, after the IV and PO administration of NaMFP, was determined to standardize the animal model. F- followed a two-compartment model and no significant differences were found between the two routes of administration. The bioavailability in dogs was only 60%. The reason for this poor bioavailability was postulated to be the delivery of drug extended beyond the principal sites of absorption of the gastrointestinal tract. Hence, we decided to characterize the absorption sites of NaMFP and to modify the CRT.

Studies on Plaque Fluoride After Use of F-Containing Dentifrices

Increased fluoride levels in plaque and saliva have been associated with improved protection against dental caries for dentifrices which contained sodium monofluorophosphate (Duckworth et al., 1992). The main aim of the present work was to test whether oral fluoride retention depended on F source after use of dentifrices containing either NaF or Na2FPO3. In study 1, plaque samples were collected from 474 subjects who had been using one of six test dentifrices for two years, and analyzed by F extraction with water. The dentifrices contained 1000 or 1500 micrograms F/g as either NaF or Na2FPO3. Significantly more fluoride was found in plaque from subjects who were using the NaF dentifrices than in plaque from subjects who were using Na2FPO3 dentifrices of the same F content. Subsets of plaque samples were large enough to divide into two parts for extraction by both acid and water. No significant difference was found between mean fluoride contents, indicating that the majority of fluoride retained in plaque from these conventional dentifrices appears to be relatively labile. The results of two small-scale human enamel studies showed that NaF dentifrices gave elevated F concentrations in plaque and saliva, respectively, compared with Na2FPO3 dentifrices of equivalent F content, consistent with the main plaque study 1. These findings demonstrate that oral F retention from dentifrices is dependent on the source of ionic fluoride and support the view that NaF dentifrices may be more clinically effective than dentifrices which contain the same amount of F as Na2FPO3.

Sodium monofluorophosphate

Sodium monofluorophosphate

Effect of supervised use of a fluoride toothpaste on caries incidence in pre-school children.

Caries prevalence of children living in Helsinki is low and little further reduction has been seen during recent years. The aim of the study was to investigate whether a supervised daily brushing at school with a fluoride toothpaste containing 1.2% sodium monofluorophosphate reduced caries incidence in a well-controlled group of nursery-school children with low caries prevalence. A total of 87 children from two nursery schools formed the test group. A group of children matched for age, baseline dfs and follow-up time, who had attended the same nursery schools just before starting this prospective study and who had brushed their teeth daily at school without toothpaste, formed a retrospective control group. After the follow-up time (mean 1.4 years), the total number of new carious surfaces was 23 in the test group (mean 0.3) and 83 in the control group (mean 0.9); the difference was significant. In the test group 72% and in the control group 62% of children were caries-free after the follow-up period. The results suggest that the use of a fluoride toothpaste as an extra daily prophylaxis reduces caries incidence in pre-school children.

An in situ enamel section model for assessment of enamel re/demineralization potential.

An enamel-section-carrying intra-oral appliance to predict the results of double-blind anti-caries studies has been developed. Initial validation was against the F concentration effect attained in a clinical trial where three sodium monofluorophosphate (SMFP) dentifrices were used. Original appliance-based work showed significant differences in remineralization between non-F and F dentifrices, but not between different F dentifrices. However, it was shown later that acidified gel-prepared lesions were not as responsive as solution-prepared lesions to de- and remineralizing processes, and lesion remineralization rates were found to be dependent on initial lesion size. An in situ cross-over study was then repeated with use of acid-solution-created lesions, and seven volunteers completed the project. Each brushed twice daily x 2 min with either 0, 1000, or 2500 ppm F, as SMFP dentifrice. After a two-week wash-out, subjects wore the appliances for four weeks. Enamel mineral content was assessed at 0, two, and four weeks via microradiography/microdensitometry, and a statistically significant dose-response was obtained between non-F and F as well as between 1000 and 2500 ppm F pastes, i.e., as per the three-year clinical trial data. Hence, the model's suitability for pre-clinical screening was confirmed. It has also been used in caries microbiological studies, in root caries investigations, and currently in chewing gum cariogenicity experiments.

Gastric effects of sodium fluoride: Comparison with sodium monofluorophosphate

Gastric effects of sodium fluoride: Comparison with sodium monofluorophosphate

Erratum to : Relationship between the Phosphatase Activity of Mutans Streptococci and Sodium Monofluorophosphate (MFP) Decomposition

Erratum to : Relationship between the Phosphatase Activity of Mutans Streptococci and Sodium Monofluorophosphate (MFP) Decomposition

ミュータンス連鎖球菌のホスファターゼ活性とモノフルオロリン酸ナトリウム（ＭＦＰ）分解の関連性

The interaction of sodium monofluorophosphate (MFP) with artificial plaque and the underlying enamel was investigated. Streptococcus mutans Ingbritt (serotype c) and Streptococcus sobrinus 6715 (serotype g) cells were grown on windowed human enamel blocks to form artificial plaque. Plaque-covered enamel and clean enamel samples were incubated anaerobically with 5 ppm (as F-) of MFP or sodium fluoride (NaF) for 48 hr.Fluoride concentration in the enamel was significantly increased in plaque-covered enamel in the presence of both MFP and NaF. More than 60% of the acquired fluoride from MFP in the enamel at a depth of 5μm was KOH-soluble fluoride. More fluoride was acquired from MFP in the enamel covered with the plaque of S. sobrinus 6715 than in that covered with the plaque of S. mutans Ingbritt.Significant degradation of MFP was detected during the growth of S. sobrinus 6715 concomitant with the fall of broth pH around 5.4 within 48 hr incubation. Optimum MFP hydrolysis by S. sobrinus 6715 and S. mutans Ingbritt occurred at approximately pH 5.0, but no detectable MFP hydrolysis was found at alkaline pH. MFP hydrolyzing activity (MFPase) was sharply inhibited by low F- concentration and was not activated by Mg2+. These data indicated that acid phosphatase, and not alkaline phosphatase, is responsible for MFP hydrolysis in mutans streptococci.

Effect of oral care habits on caries in adolescents.

Data on toothbrushing habits were collected during a 3-year caries clinical trial of sodium monofluorophosphate toothpastes in Lanarkshire, Scotland, involving 3,005 schoolchildren of mean age 12.5 years at baseline. Stated normal brushing frequency and oral rinsing method after brushing were recorded. Half the panel indicated they rinsed their mouths after toothbrushing using a beaker. The proportion of the panel brushing once per day or more increased during the trial. Differences in oral habits were observed between the sexes, with 42% of girls and 52% of boys being non-beaker rinsers and 73% of girls, but only 44% of boys, brushing their teeth at least twice per day. Twice-a-day brushers had a consistently lower caries increment than less frequent brushers. This was also seen in the baseline prevalence data, but did not account for all incremental differences noted. Subjects using beakers had consistently higher increments than non-beaker rinsers. Again, this difference could not be explained by variations in baseline prevalence. Differences in the caries increment were also observed between boys and girls, these appearing to be linked both to the cumulative effect of male/female habit variations plus a difference in the baseline caries prevalence. A dose response to the three fluoride levels, i.e 1,000, 1,500, and 2,500 ppm F, was seen for the different habit combinations which again could not be explained by differences in the baseline caries prevalence.

Clinical and Microbiological Effects of a Sanguinaria‐Containing Mouthrinse and Dentifrice With and Without Fluoride During 6 Months of Use

The purpose of this study was to test the efficacy and safety of sanguinaria-containing regimens with and without fluoride using the American Dental Association guidelines for evaluating chemotherapeutic agents. The study was a 6-month, double-blind, 4-cell, placebo-controlled, parallel investigation involving 120 subjects. Following screening procedures, subjects were randomly assigned to 4 groups. Group 1 received a dentifrice containing 0.075% sanguinaria extract (SaE) and 2.0% zinc chloride (ZnCl2) in a dicalcium phosphate base, plus an oral rinse containing 0.03% SaE and 0.2% ZnCl2. Group 2 received identical products without SaE or ZnCl2. Group 3 received a dentifrice containing 0.8% sodium monofluorophosphate, 0.075% SaE, and 0.05% ZnCl2 in a silica base, plus an oral rinse containing 0.03% SaE and 0.2% ZnCl2. Group 4 products were identical to those of Group 3 but without SaE and ZnCl2. Supragingival plaque and gingival inflammation were scored at 0, 1, 2, 1.5, 3, 4.5, and 6 months; bleeding upon probing was measured at 1, 1.5, 3, and 6 months. Microbiological samples were taken from plaque, tongue, and cheek areas. The active products produced statistically significantly lower scores than the placebo agents for all indices (P less than .0001). Six-month plaque scores were 13.1% lower for Group 1 and 17.4% lower for Group 3 compared to placebo products. When the Plaque Severity Index was applied, the percentage reductions were 33% for Group 1 and 41% for Group 3 compared to placebos. Gingival inflammation scores were 16.7% lower for Group 1 and 18.1% lower for Group 3 at 6 months compared to placebo scores.(ABSTRACT TRUNCATED AT 250 WORDS)

Dentine hypersensitivity: a review

Dentine hypersensitivity is a relatively common pain condition. Local pulpal inflammation, traumatic oral hygiene and dietary habits have been considered in the etiology of dentine hypersensitivity. Dentine hypersensitivity is probably caused by a change in fluid flow in the dentinal tubules, which in turn excites the nerve endings located at the pulp-dentine border. Consequently, treatment success would depend on the prevention of fluid flow across the dentinal tubules (sodium fluoride, stannous fluoride, sodium monofluorophosphate, strontium chloride, sodium citrate, potassium oxalate, and resins/adhesives), or on the desensitization of the nerve endings located at the pulp-dentine border (potassium nitrate). Although a wide variety of treatment methods have been available, clinical data is characterized with ambiguity, warranting further research of the factors which could possibly be implicated in the occurrence of dentine hypersensitivity.

Comparison between Evaluation Methods for the Anti-Caries Efficacy of Monofluorophosphate-Containing Dentifrices

A comparison is described of three methods of preclinical assessment of potential anti-caries efficacy for topical fluoride treatments. Methods are compared using dentifrices containing 1,000, 1,500 and 2,500 ppm F as sodium monofluorophosphate (SMFP). These formulations have been shown elsewhere to give a statistically significant dose response of increasing anti-caries efficacy [Stephen et al., 1988]. An in situ enamel insert model, oral fluoride pharmacokinetics and F uptake to demineralised enamel are all shown to correlate with clinical efficacy for the test dentifrices studied.