Osteoporos Int (2005) 16: 1576–1582
DOI 10.1007/s00198-005-1870-z
O R I GI N A L A R T IC L E
Assessment of teeth as biomarkers for skeletal fluoride exposure
A.P.G.F. Vieira Æ M. Mousny Æ R. Maia Æ R. Hancock
E.T. Everett Æ M.D. Grynpas
Received: 16 July 2004 / Accepted: 1 February 2005 / Published online: 30 March 2005
International Osteoporosis Foundation and National Osteoporosis Foundation 2005
Abstract Skeletal fluorosis and dental fluorosis are diseases related to fluoride (F) ingestion. Bone is the largest
storage site of F in our body. Therefore, bone F concentrations are considered biomarkers for total F body
burden (exposure). However, difficult accessibility limits
its use as a biomarker. Thus, a more accessible tissue
should be considered and analyzed as a biomarker for
total F body burden. The objective of this study, which
was divided into two parts, was to evaluate teeth as a
biomarker for skeletal F exposure. In part 1 of the study,
70 mice of three different strains (SWR/J, A/J and
129P3/J) were exposed to different levels of water fluoridation (0, 25, 50 and 100 ppm). Bone (femora and
vertebrae) and teeth from these mice were then analyzed
for F concentration using Instrumental Neutron Activation Analysis (INAA). In part 2 of the study, human
teeth (enamel and dentin) and bone from 30 study subjects were collected and analyzed for F concentration
using INAA. Study subjects lived in areas with optimum
levels of water fluoridation (0.7 and 1 ppm) and under-
A.P.G.F. Vieira Æ M.D. Grynpas
Faculty of Dentistry, University of Toronto,
Toronto, Ontario, Canada
A.P.G.F. Vieira Æ M.D. Grynpas (&)
Samuel Lunenfeld Research Institute,
Mount Sinai Hospital, 600 University Avenue Room 840,
Toronto, Ontario, M5G 1X5, Canada
E-mail: [email protected]
Tel.: +1-416-5864464
Fax: +1-416-5861554
M. Mousny
Department of Orthopedic Surgery,
Université Catholique de Louvain, Louvain, Belgium
R. Maia
Universidade Federal do Ceara, Ceara, Brazil
R. Hancock
Department of Chemical Engineering and Applied Chemistry,
University of Toronto, Toronto, Ontario, Canada
E.T. Everett
Schools of Dentistry and Medicine,
Indiana University, Indianapolis, Indiana, USA
went therapeutic extraction of their unerupted third
molars. The values of bone and teeth F concentration
were correlated for parts 1 and 2 of this study. The results showed that in the animal model, where animals
were exposed to a wide range of F in their drinking
water, tooth [F] correlated with bone [F]. However, no
correlation was seen between bone and enamel F concentrations or between bone and dentin F concentrations in the human samples. Therefore, teeth are not
good biomarkers for skeletal F exposure in humans
when exposure is confined to optimum levels of F in the
drinking water.
Keywords Biomarker Æ Dentin Æ Enamel Æ Fluoride Æ
Mouse model
Introduction
The addition of fluoride to community drinking water
will stand as a major public health measure by substantially reducing dental caries and tooth loss and is
hallmarked as one of the most successful public health
disease prevention programs ever initiated [1]. Fluoride
(F) can be found at varying concentrations in water
(naturally present or supplemented), food, and dental
products. It is ‘‘virtually impossible to find ‘nonfluoridated’ communities, due to the many opportunities for
exposure to fluoride’’ [2].
Fluoride is a natural component of the biosphere, the
13th most abundant element in the earth’s crust [3], and
is used in the treatment of osteoporosis [4]. Among its
characteristics, F has a high affinity for mineralized tissues, which means it can be found in teeth and bone
(Those contain approximately 99% of the body burden
of fluoride F) [5].
Humans and animals are typically exposed to the F ion
without any adverse effect. Fluoride can be therapeutically used in low doses for dental caries prevention or in
high doses for the treatment of osteoporosis [4, 6].
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However, when very high doses of F (higher than the
doses used for the treatment of osteoporosis) are used,
skeletal fluorosis can develop [5]. Another undesirable
effect of high levels of F is dental fluorosis [5]. High and
potentially harmful F levels may occur in air, soil, and
water [7].
Dental fluorosis (DF) can occur when greater than
optimal fluoride is ingested during critical periods of
tooth enamel formation. This exposure can be either
short term and coincide with amelogenesis or chronic,
which encompasses a larger window of opportunity [8, 9,
10]. It is a disturbance primarily affecting enamel during
formation, but can also affect dentin [11]. Microscopically, fluorotic enamel shows a subsurface porosity,
whereas the clinical appearance varies from slight white
lines to irregular cloudy areas [12]. With increasing
severity, the white areas merge, and loss of the enamel
may occur [13].
Skeletal fluorosis (SF) is a more serious condition
compared to DF. The most common feature of SF is the
irregular thickening of the bones in the central skeleton,
due to periosteal sleeves of abnormally structured osseous tissue, osteophytosis, mineralization of tendons and
muscle attachments, and bridging between the edges of
the vertebral bodies [7]. In SF, fluoride is ingested during
periods of bone modeling (growth) and/or remodeling.
Bone is the largest pool of F in our body [14].
Therefore, bone F concentration is considered a marker
for total F body burden (biomarker of exposure).
However, this tissue is difficult to access, and the simplicity of the collection is an important advantage when
choosing a biomarker of exposure [15]. Consequently, a
more accessible tissue should be considered as a historic
(long-term) biomarker for total F body burden. Some
studies have been developed looking into the use of
fingernails as a biomarker for F exposure [16]. However,
nails, as well as hair, are recent (median term) biomarkers [17]. Teeth can be more accessible than bone.
Additionally, the apparent similarity between the F
concentrations in bone and dentin is intriguing and deserves further research attention [14].
Dentin, especially coronal, may be the best marker
for the estimation of chronic F intake and the most
suitable indicator of total F body burden. Dentin contains only the F that has been incorporated through
systemic ingestion. It does not normally undergo
resorption and continues to accumulate F throughout
life. As well, dentin is more easily obtained than bone
and is also protected from F exposure in the oral cavity
and surrounding bone by the covering enamel and
cementum [18, 19]. The objective of this study is to
evaluate the use of tooth structure, especially dentin, as a
biomarker for skeletal F exposure.
Materials and methods
This study was divided in two parts: (1) an animal model
study and (2) a human study. In the animal model, a
wide range of drinking water F concentration was
investigated, while in the human part of this study, a
more narrow range of drinking water F concentration
was observed.
Part 1: animal model study
A total of 72 male mice, from three different strains (SWR/
J, 129P3/J and A/J), were submitted to four different levels
of F treatment (0, 25, 50 and 100 ppm of F in the drinking
water) from weaning (4 weeks of age) for a period of
42 days. Mice were fed regular laboratory rodent diet that
contained a F concentration ranging from 5 to 8 lg/gm.
Mice were allowed water and food ad libitum. Each
treatment group originally consisted of six male mice.
After the F treatment, the mice were killed, and their
femora, lumbar vertebrae and upper central incisors
were analyzed for F concentration using instrumental
neutron activation analysis (INAA). Samples were
cleaned of soft tissue. In INAA, each sample is bombarded with thermal neutrons that produce short-lived
radioisotopes from the elements in the sample. These
radioisotopes decay with specific half-lives, emitting
gamma rays of discrete and characteristic energies. The
relative amounts of gamma rays detected are proportional to the concentrations of the elements in the
sample [20]. INAA is capable of measuring F concentration above 50 ppm (0.05%) to the 10 ppm level
(0.01%). Its typical precision and accuracy vary from
±2 to ±10%, depending on the element, the nature of
the sample matrix and the absolute concentration of the
element [21].
Part 2: human study
Patients from Toronto, Canada (drinking fluoridated
water at 1 ppm F) and Fortaleza, Brazil (drinking
fluoridated water at 0.7 ppm F), who were scheduled for
surgical removal of their unerupted third molars, were
recruited for this study. Patients were asked to donate
their extracted teeth and the alveolar bone that was removed in order to extract successfully the impacted
teeth. Additionally, patients were asked to answer a
questionnaire about their place of residence. Ethical
approval for this research was granted by the University
of Toronto ethical committee and by the Federal University of Paraiba.
Teeth collected in Canada were kept frozen ()20C)
between collection and analysis. However, teeth originating from Brazil were sent to Canada (where analysis
was performed) wrapped in gauze (soaked in thymol)
and were subsequently frozen at )20C.
Teeth were defrosted at room temperature overnight,
embedded in epoxy resin (Epoxycure resin, Buehler,
Markham, Canada) and sectioned using a low speed saw
(Isomet, Buehler Ltd., Lake Bluff, Ill.) as previously
described [22] (Fig. 1).
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Fig. 1 Tooth preparation
Each patient had between two and four third molars
extracted. Each patient, but not each extraction site, was
utilized as a unit of analysis. Therefore, dentin samples
from the buccal and lingual side of all extracted teeth for
each patient were pooled and collectively analyzed for F
concentration using INAA. The same procedure was
used for enamel samples. The bone collected from each
patient, obtained from all extraction sites, was also
collectively analyzed using INAA. An average of 160 mg
of dentin, 290 mg of enamel and 120 mg of bone per
subject was sent for analysis.
Statistics
Descriptive statistics, Spearman’s correlation and
Kruskal-Wallis test were used when appropriate. Significant values were set at P £ 0.05. Statistical analysis
was done with the use of statistical analysis software
(SPSS for Windows, SPSS Inc., Chicago, Ill.).
Results
Part 1
The collected incisor teeth, vertebrae and femora from
the 12 treatment groups (three mouse strains and four
fluoride levels) were analyzed independently for F concentration. The overall tooth F concentration from all
12 groups varied between 76 and 2,385 ppm, while F
concentration in mice vertebrae varied between 71 and
2,114 ppm and between 85 and 3,071 in mice femur.
Table 1 presents the descriptive statistics for part 1.
As the data were not normally distributed, the
Spearman correlation test (non-parametric) was utilized
to evaluate the correlation between incisor F concentration, vertebrae F concentration and femur F concentration. Correlation was also performed between F
treatment (water F concentration) and tooth and bone F
concentration.
A strong and significant correlation was found between teeth F concentration and vertebrae F concentration (rs=0.930, P <0.001), as well as between teeth F
concentration and femur F concentration (rs=0.943, P
<0.001). The F treatment group (level of F in drinking
water) also correlated very strongly with the teeth F
concentration (rs=0.952, P <0.001), vertebrae F concentration (rs=0.957, P <0.001) and femur F concentration (rs=0.962, P <0.001) (Table 2). The
Kruskal-Wallis test also showed, confirming the results
from the correlation test, a significant difference among
all the F treatment groups (0, 25, 50 and 100 ppm) when
compared to teeth and bone F concentration
(P >0.001). The data showed that the higher values of F
in the drinking water presented the higher values in teeth
and bone F concentration.
When strains were evaluated separately, the correlation between teeth F concentration and bone F concentration (vertebrae and femora) was also significantly
present; however, the rs values were slightly lower for the
129P3/J strain (Table 3).
When only the mice with no fluoride supplementation
in the water but with regular F ingestion through laboratory rodent diet (0 ppm F treatment group) were
analyzed, no correlation was found between teeth F
concentration and vertebrae (rs=0.183, P =0.47) and
femur (rs=0.176, P =0.48) F concentration. Tooth F
concentration varied between 76 and 196 ppm, while
vertebrae F concentration varied between 71 and
136 ppm and femora F concentration varied between 85
and 187 ppm.
Part 2
A total of 30 patients from Toronto, Canada, and
Fortaleza, Brazil, were included in this study. Patients
ranged in age between 13 and 24 years, with 18 years
being the average age. Forty percent of the subjects were
males.
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Enamel F concentration varied between 0 and
192 ppm, while dentin F concentration varied between
59 and 374 ppm, and bone F concentration varied between 0 and 396 ppm. Table 4 presents the descriptive
statistics for part 2.
The Spearman correlation test was performed, and
no correlation was seen between bone F concentration
and enamel (rs=0.069, P =0.72) or dentin (rs=0.234, P
=0.21) F concentrations. The only significant correlation observed was between enamel and dentin F concentration in the same tooth (rs=0.651, P<0.001)
(Table 5).
Discussion
This is the first study to evaluate the use of tooth (enamel and dentin) F concentration as a long-term biomarker for skeletal F exposure in humans. Short-term
biomarkers (e.g., hair and nail) for F exposure have already been studied in the literature [16, 23, 24]. In North
America, third molars (wisdom teeth) are routinely removed from young adult patients. These teeth have the
potential to be used as a screening tool for patients at
risk (e.g., patients living in endemic fluorosis areas).
Table 1 Descriptive statistics.
Tooth [F]
Drinking
water [F]
Mouse strain
No.
Mean
SD
Range
0
All strains
A/J
129P3/J
SWR/J
All strains
A/J
129P3/J
SWR/J
All strains
A/J
129P3/J
SWR/J
All strains
A/J
129P3/J
SWR/J
18
6
6
6
16
6
4
6
18
6
6
6
18
6
6
6
131.3
147.8
132.5
113.7
505.2
444.2
584.0
513.7
829.9
944.3
633.0
912.3
1,847.9
2,110.3
1,632.7
1,800.8
40.8
44.0
45.3
31.0
118.9
79.0
193.9
64.1
217.8
35.1
204.3
219.0
294.1
219.5
213.9
243.2
76–196
97–196
81–189
76–150
341–872
341–560
456–872
439–591
264–1,317
894–1,001
264–817
718–1317
1,377–2,385
1,827–2,385
1,377–1,927
1,472–2,183
All strains
A/J
129P3/J
SWR/J
All strains
A/J
129P3/J
SWR/J
All strains
A/J
129P3/J
SWR/J
All strains
A/J
129P3/J
SWR/J
18
6
6
6
16
6
4
6
18
6
6
6
18
6
6
6
101.4
90.7
116.2
97.5
488.9
384.3
454.3
513.7
850
667.0
787.5
1097.3
1,613.3
1,596.7
1,530.8
1,712.3
17.8
15.7
14.4
14.2
132.5
32.7
52.9
64.1
209.1
71.7
83.0
134.7
263.0
243.7
274.4
283.4
71–136
71–119
100–136
72–109
351–841
351–435
405–526
439–591
568–1,302
568–747
655–889
947–1,302
1,241–2,114
1,413–1,957
1,241–1,950
1,320–2,114
All strains
A/J
129P3/J
SWR/J
All strains
A/J
129P3/J
SWR/J
All strains
A/J
129P3/J
SWR/J
All strains
A/J
129P3/J
SWR/J
18
6
6
6
16
6
4
6
18
6
6
6
18
6
6
6
139.7
119.3
176.8
122.8
730.7
557.3
748.3
892.3
1,273.5
1,138.5
1,099.5
1,582.5
2,441.2
2,433.7
2,438.5
2,451.3
31.1
21.0
7.5
17.3
170.9
63.4
46.0
121.2
275.9
76.7
102.1
264.0
375.0
505.4
320.1
346.5
85–187
85–143
165–187
95–142
483–1,063
483–659
716–814
745–1,063
937–2,071
1,046–1,261
937–1,195
1,288–2,071
1,531–3,071
1,530–3,071
2,056–2,891
2,139–3,046
25
50
100
Vertebrae [F]
0
25
50
100
Femur [F]
0
25
50
100
Part 1: mouse study. [F] =
fluoride concentration (ppm)
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Table 2 Correlation table (Spearman correlation test). Part 1:
mouse study. [F] = fluoride concentration (ppm). *Two mice from
the 129P3/J strain (25 ppm F treatment group) died before the end
of the F treatment; thus, only 70 mice were evaluated in this study
(only 4 in the 129P3/J 25 ppm F treatment group)
[F]
teeth
[F] teeth
[F] vertebrae
Correlation
coefficient (rs)
Sig. (2-tailed)
No.
Correlation
coefficient (rs)
Sig. (2-tailed)
No.
[F]
vertebrae
[F]
femora
0.930
0.943
0.001
70*
0.930
0.001
70*
0.964
0.001
70*
0.001
70*
Additionally, the loss of teeth in the elderly (e.g., periodontal diseases) is not uncommon. Therefore, lost teeth
from osteoporotic patients treated with fluoride could be
used as an indicator of fluoride body burden.
Dentin F concentration profiles change with age and
appear to be similar to those of cortical bone [14, 25].
Dentin has been proposed as a biomarker for the body
burden of F in bone for at least a decade [14]. However,
this hypothesis has never been tested.
This study showed that in humans and mice exposed
to narrow ranges of F ingestion, no correlation exists
between tooth F concentration and bone F concentration. In mice exposed to a wide range of F in their diet,
tooth F concentration correlated with bone F concentration, confirming the use of tooth as a biomarker for
skeletal F exposure. The levels of F to which humans
were exposed (0.7–1.0 ppm of F) are considered optimum levels for caries prevention.
One of the explanations for the lack of correlation
between bone and tooth F concentration in humans may
rely on the fact that there was a small range of F concentration in their mineralized tissue, which was due to a
limited exposure of this group to fluoride. Bone F concentration in part 1 (mice study) varied between 71 and
3,071 ppm, while bone F concentration in part 2 (human
study) varied between 0 and 395 ppm. Additionally, in
mice when the range of bone F concentration is reduced
(mice exposed to water with no F added to it and with a
range of bone F concentration similar to humans), no
Table 3 Correlation table (Spearman correlation test). Three different mice strains (part 1). [F] = fluoride concentration (ppm)
Tooth [F]
Mouse strain
[F] vertebrae
[F] femora
Correlation
coefficient (rs)
Sig. (2-tailed)
No.
Correlation
coefficient (rs)
Sig. (2-tailed)
No.
A/J
129P3/J
SWR/J
0.971
0.902
0.968
0.001
24
0.967
0.001
24
0.895
0.001
24
0.975
0.001
24
0.001
24
0.001
24
Table 4 Descriptive statistics (part 2). Human study. [F] = Fluoride concentration (ppm)
Bone [F]
Enamel [F]
Dentin [F]
No.
Mean
SD
Range
30
30
30
175.7
102.8
215.3
88.2
53.3
75.0
0–396
0–192
59–374
correlation was seen between tooth F concentration and
bone F concentration.
The effects of F on bone have been studied in different animal models. There are some variations in the
reported results, which may be due to a different response to F according to the species [26]. These variations could be confirmed in our study. Mice were
exposed to water F concentration varying from 0 to
100 ppm, while humans were exposed to optimum (for
caries prevention) water F concentration (0.7 and
1 ppm). However, despite the water F levels in the mice
study being approximately 100 times larger than in the
human study, the range of bone F concentration in mice
was only eight times larger than in humans. This suggests that humans and mice respond differently to F,
which may then explain why a correlation is seen between bone and teeth in mice and not in humans.
Additionally, mice continually erupt their incisors
and, unlike humans, mice bones do not have harvesian
remodeling. Mice grow continuously, albeit at a greatly
reduced velocity following maturity. In humans, dentin
(secondary dentin) continues to be deposited throughout
life, although very slowly after tooth eruption. Human
bone constantly models and remodels throughout life;
however, in young individuals modeling (growing) is
more important than remodeling, while in older individuals (mature), remodeling is more important than
modeling.
However, the lack of correlation in the human study
is probably due to the limited range of F intake and F
concentration in human mineralized structure, rather
than to the difference in response to F and/or the difference in bone and teeth formation and maturation in
both species. High levels of F, in the levels used for the
treatment of osteoporosis, have shown increased bone
mineral density [4], while the F levels used for caries
Table 5 Correlation table (Spearman correlation test). Part 2 (human study). [F] = fluoride concentration (ppm)
Bone [F]
Bone [F]
Enamel [F]
Correlation
coefficient (rs)
Sig. (2-tailed)
No.
Correlation
coefficient (rs)
Sig. (2-tailed)
No.
Enamel [F]
Dentin [F]
0.069
0.234
0.717
30
0.069
0.213
30
0.651
0.717
30
0.001
30
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prevention have been shown to have very little affect on
the bone fracture rate [27].
While it seems that 42 days (the time in which the
mice were exposed to F) is a short period, it is important
to know that humans and mice were exposed to F for a
fairly long time (chronic exposure). The life span of mice
is about 2 years (104 weeks), while the human life span
is about 80 years. Mice were exposed to F for 42 days
(6 weeks) from the age of 4 weeks. Therefore, mice were
71 days old (10 weeks) when they were killed. Transforming mice age into ‘‘human years,’’ we can see that
the mice exposure to F was not acute, but rather
chronic. Additionally, this chronic exposure was present
during the time of tooth formation. In relative ‘‘human
years,’’ mice started to receive F when they were about
3 years of age and were killed when they were 8 years of
age, receiving F for 5 years.
Regarding human exposure to F, it is important to
know that water F concentration of 4 ppm or higher is
common in communities with a high prevalence of
dental fluorosis [5, 7]. For the treatment of osteoporosis,
patients normally ingest 50 to 90 mg of NaF a day. A
50-mg dose of NaF has 22.6 mg of F, whereas 90 mg of
NaF represents 40.1 mg of F.
It is interesting to note that the high F doses received
by mice represent doses to which individuals living in
endemic areas of dental fluorosis and receiving F treatment for osteoporosis are exposed. Rodents need a F dose
five times higher than humans to get the same serum F
level in their blood stream [28]. Therefore, water F concentration of 100 ppm for mice is equivalent to a water F
concentration of 20 ppm for humans. If an individual is
ingesting fluoridated water at 20 ppm (equivalent to
100 ppm in mice), a total dose of 40 mg of F a day can be
expected [20·2 (liter of water a day)]. With this information in mind, it is apparent that mice ingesting water
with a F concentration between 50 and 100 ppm (equivalent to 20 and 40 mg/day of F for humans) are, in fact,
ingesting F levels similar to the treatment of osteoporosis
in humans (between 22.6 and 40.1 mg/day). Furthermore, mice ingesting water with 25 ppm of F are ingesting
a human dose equivalent to 5 ppm of F (commonly found
in areas of endemic dental fluorosis).
The most challenging aspects of this study were to
obtain bone and teeth from the same patient as well as to
collect tooth samples that had not been exposed to
topical F (e.g., erupted teeth in contact with the oral
environment). In order to overcome these difficulties, the
unerupted third molar (wisdom tooth) model was used.
In this model, teeth that were not exposed to the oral
environment (unerupted teeth) and bone from the same
area could be collected simultaneously from each patient. Alveolar bone is normally removed to gain access
to the unerupted third molar [29]. The authors are aware
of the limitations of this study: (1) the narrow range of F
concentration to which individuals were exposed and (2)
the limitation on the site of bone collection (alveolar
bone). However, despite these limitations, the authors
cannot propose a better experimental approach to test
the hypothesis that teeth are good biomarkers for skeletal F burden.
The ideal study protocol would include areas where
the populations naturally ingest very high levels of F
(e.g., endemic areas of dental fluorosis). As these populations are commonly located in very underprivileged
areas, extraction of unerupted third molars is not a
common dental treatment. Offering this type of dental
treatment to those communities, together with a more
comprehensive dental treatment, would make this study
protocol possible. However, due to the economical
limitations of this approach (the costs involved), the
authors do not foresee this as a real possibility in these
communities in the short term.
A different approach would be to use erupted teeth
from older individuals in these communities (simple
extractions are common dental treatment in these communities) or from older individuals receiving F for the
treatment of osteoporosis. While there are some problems using erupted teeth while analyzing enamel, dentin
samples can be used to evaluate the F content in teeth.
However, during simple tooth extraction, bone is not
normally removed. It would be ethically inappropriate
to remove bone samples from these patients. Therefore,
once again, the authors cannot foresee this approach as
being feasible.
Therefore, despite the limitations of our study (narrow F intake in the human group), we believe that this
study has the most appropriate protocol possible at the
moment to evaluate the correlation between tooth and
skeletal F concentrations.
Nonetheless, the small range of F concentration in
the human mineralized tissues provides a baseline for
communities that are optimally fluoridated. The use of
mice in this study allowed us to have a larger range of F
exposure, enabling us to investigate more extreme F
exposure.
Only a few papers have investigated the F concentration in teeth and bone of rodents with different levels
of F ingestion [30, 31], but the correlation between F
levels in mice teeth and bones has not been evaluated.
The use of three different mice strains allowed us to
control for differences in genetic F susceptibility in this
model. Among the three strains, the 129P3/J showed a
lower correlation value between teeth and bone F concentration when compared with the other two strains.
This suggests that those mice strains react differently to
F intake; however, the differences between strains were
very limited. F susceptibility may play an important role
in the way humans respond to F ingestion. For example,
about 25% of patients undergoing treatment with F for
osteoporosis failed to respond adequately [7, 32, 33].
Additionally, some data suggest that dental fluorosis is
more prevalent among African-Americans than among
other ethnic groups in the same community [34, 35, 36].
It is also known that not all patients exposed to high
levels of F develop skeletal and/or dental fluorosis.
As different types of bone have different turnover
rates [37, 38], the site of bone collection is also important
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when evaluating bone F concentration [14]. However, F
concentration from different parts of the human skeleton has shown comparable F concentration [39]. In part
2 of this study (human study), only alveolar bone was
collected.
In conclusion, the results of this study showed that
when humans and mice are not being exposed to high
levels of F (narrow range of F exposure), teeth are not
good biomarkers for skeletal F exposure. However,
teeth can be used as a biomarker for skeletal F exposure
in mice treated with high levels of F (drinking water),
demonstrating the possibility of using teeth as a biomarker for skeletal F exposure in humans exposed to
greater than optimal levels of F. Further investigation
utilizing subjects exposed to higher levels of F is necessary to confirm the utilization of teeth F concentration
as a biomarker for skeletal F exposure in humans.
Acknowledgments We would like to thank the oral maxillo-facial
surgery departments at the Faculty of Dentistry at the University of
Toronto and Federal University of Ceara for the samples utilized
in this research. We would also like to thank Ms. Deidra Faust
for her technical assistance during this study and Dr. Angeles
Martienz-Mier for F analyses on food and water samples. This
work was funded by a grant from the Canadian Institute of
Health Research (CIHR) and by the NIH/NIDCR (R01DE014853) to ETE. AV is the recipient of Harron and Connaught
Scholarships.
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