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16th Jun 2001: BMJ
BMJ 2001;322:1486 (16 Jun )
Letters - Water
fluoridation
- Meta-analysis of
fluoridation and fractures has been done
- Critical
difference was overlooked
- Clearer evidence
of benefits and risks is needed
- Government
should meet commitment made in white paper
- Authors' reply
- Results should
be viewed with concern rather than applause
- Authors' reply
- Little is known
about the safety of fluoridation
- Ireland has less
decay in non-fluoridated communities
Meta-analysis of
fluoridation and fractures has been done
EDITOR The article
by McDonagh et al is valuable but not necessarily
new in the area of fractures.1 They conclude that
the evidence relating fluoridation to fractures is
weak and shows no significant effect either way.
This is identical to the conclusion that we
published in a 1999 meta-analysis not cited by
McDonagh et al but listed on Medline.2 This study
located 26 studies in this area, compared with their
20, and reported a relative risk for fracture of
1.02 (95% confidence interval 0.96 to 1.09).
Interestingly, sex, urbanicity index, and the
quality (but not duration) of the study explained
25% of the variation between studies in
meta-regression.
Further work in
this area will need to be done at an individual
level to advance this field, but even this is
problematic given the paper by Phipps et al in the
same issue of the journal, which reports on a very
large cohort of women.3 Nevertheless, it seems
unlikely that water fluoridation to 1 ppm has any
significant effect on the incidence of fractures at
a population level based on the current (albeit
weak) evidence.
Graeme Jones,
senior research fellow.
Menzies Centre for
Population Health research, GPO Box 252-23, Hobart,
Tasmania, Australia G.Jones@utas.edu.au
Competing
interests: None declared.
1. McDonagh MS,
Whiting PF, Wilson PM, Sutton AJ, Chestnutt I,
Cooper J, et al. Systematic review of water
fluoridation. BMJ 2000; 321: 855-859[Abstract/Full
Text]. (7 October.)
2. Jones G, Riley
M, Couper D, Dwyer T. Water fluoridation, bone mass
and hip fracture: a quantitative overview of the
literature. Aust N Z J Public Health 1999; 23:
34-40[Medline].
3. Phipps KR,
Orwoll ES, Mason JD, Cauley JA. Community water
fluoridation, bone mineral density, and fractures:
prospective study of effects in older women. BMJ
2000; 321: 860-864[Abstract/Full Text]. (7 October.)
Critical
difference was overlooked
EDITOR I wish to
comment on the paper by McDonagh et al on
fluoridation and the study by Phipps et al on bone
fracture. 1 2 Although the paper by McDonagh et al
deals a very serious blow to fluoridation on the
basis of their findings of a much lower benefit for
caries reduction than previously claimed and a much
higher level of dental fluorosis than is acceptable,
the authors do not make it clear that dental
fluorosis is an indication of a toxic effect of
fluoride, in a similar way that the blue line on
gums is an indicator of lead poisoning. This raises
the question of what other enzymes and proteins
might be poisoned. The paper by McDonagh et al is
only a partial scientific analysis. They did not
consider work on the pineal or thyroid gland or many
animal experiments showing an effect of fluoride on
the brain.
On the basis of
their meta-analysis, McDonagh et al claim that there
is no evidence of a relation between hip fracture in
elderly people and fluoridation but mischaracterise
some of the key studies. For example, they indicated
that Li et al showed no association.3 Li et al
showed, however, that at above 1.5 ppm hip fracture
rates were doubled and above 4 ppm they were
tripled. Although I pointed this out to McDonagh et
al twice, they still report no association.
The most disturbing
aspect of the study by Phipps et al is how much
attention is given to the decrease in hip fracture
incidence and how little to the increase in wrist
fracture. The ostensible reason for this is that the
32% increase in wrist fracture is deemed
insignificant. However, the supposed insignificance
is based upon the fact that the 95% confidence
interval is given as 1.00 to 1.71. Had the interval
been 1.01 to 1.71, the increase would have been
deemed significant. Bearing in mind that this result
is achieved after many adjustments, the claim that
long term exposure to fluoridated drinking water
does not increase the risk of fracture is cavalier.
It is also intriguing that McDonagh et al reported
the study by Phipps et al about wrist fractures as
significant with a confidence interval of 1.02 to
1.71.
Overall, it is
unfortunate that McDonagh et al have managed to
convey the message that there is no evidence of harm
from fluoridation, when in fact there is mixed
evidence of harma critical difference.
Paul Connett,
professor of chemistry.
St Lawrence
University, Canton, New York, NY 13617, USA
Competing
interests: PC is a founding member of the Fluoride
Action Network, an international coalition of
citizens and scientists seeking an end to
fluoridation worldwide. With his son he runs the web
page www.fluoridealert.org.
1. McDonagh MS,
Whiting PF, Wilson PM, Sutton AJ, Chestnutt I,
Cooper J, et al. Systematic review of water
fluoridation. BMJ 2000; 321: 855-859[Abstract/Full
Text]. (7 October.)
2. Phipps KR,
Orwoll ES, Mason JD, Cauley JA. Community water
fluoridation, bone mineral density, and fractures:
prospective study of effects in older women. BMJ
2000; 321: 860-864[Abstract/Full Text]. (7 October.)
3. Li Y, Liang C,
Siemenda C, Ji R, Sun S, Gao J, et al. Effect of
long term exposure to fluoridation in drinking water
on risks of bone fractures. 1999. (Unpublished
report, submitted by author.)
Clearer evidence
of benefits and risks is needed
EDITOR The
systematic review by McDonagh et al indicates that
the benefits and risks of water fluoridation balance
each other in that a median of six people would need
to receive fluoridated water for one to benefit
while six people would have to be exposed to it for
one additional person to develop dental fluorosis.1
It also shows that in artificially fluoridated areas
on average 48% of the population has this condition.
Since dental fluorosis, whether of aesthetic concern
or not, is the first visible sign of poisoning by
fluoride, which is as toxic as arsenic and lead,
this shows that about half the population in these
areas is suffering from some degree of harm. This
suggests that water fluoridation is an unacceptable
method of reducing dental decay.
The benefits may be
overestimated whereas the risks may be grossly
underestimated. A confounding factor that was
repeatedly pointed out to the review panel but not
taken into account is that fluoride delays tooth
eruption. In comparing children of similar age, this
biases the results in favour of fluoride.2
The review by
McDonagh et al does point out the possibility of
adverse effects of fluoride on the thyroid gland.
Fluorine displaces iodine from its compounds and may
be at least one of the factors, if not the major
one, in causing the delay in tooth eruption. It may
also be a factor in the increased neonatal death
rate described by Schatz in a fluoridated area of
Chile,3 a paper that was submitted to the review but
does not seem to have been commented on. Birmingham
and the West Midlands, fluoridated since the early
1960s, have one of the highest neonatal death rates
in Britain,4 and an exceptionally high rate of
diabetes.5
Since the
established view is that water fluoridation is
perfectly safe, little research into possible
adverse effects has been carried out on human
populations drinking artificially fluoridated water,
and correlations are not made between increasing
prevalences of illness and water fluoridation. There
is, however, a large body of experimental and animal
evidence, studies that fell outside the remit of the
review by McDonagh et al, which attest to the toxic
effects of fluoride on the stomach, kidneys,
pancreas, thyroid, brain and immune system, as well
as on bones and teeth. Since animal studies are the
gold standard of drug safety testing, this evidence
should also be considered before mass medicating any
further sections of the community. If the York
review shows anything, it is that there should be a
moratorium on all current fluoridation schemes until
clearer evidence of benefits and risks becomes
available.
Sheila L M Gibson,
hospital practitioner.
Robin G Gibson,
consultant physician.
Glasgow Homeopathic
Hospital, Glasgow G12 0XQ
Competing
interests: SLMG is medical adviser to the National
Pure Water Association and member of an advisory
panel to the systematic review of water
fluoridation. RGG none declared.
1. McDonagh MS,
Whiting PF, Wilson PM, Sutton AJ, Chestnutt I,
Cooper J, et al. Systematic review of water
fluoridation. BMJ 2000; 321: 855-859[Abstract/Full
Text]. (7 October.)
2. Gibson SLM,
Gibson RG. Water fluoridation and tooth decay in 5
year olds. BMJ 1998; 316: 231.
3. Schatz A.
Increased death rates in Chile associated with
artificial fluoridation of drinking water, with
implications for other countries. Journal of the
Arts, Science and Humanities 1976; 2: 1-17.
4. Settatree R,
Wyldes M, Tonks A. Stillbirth and neonatal death
1991-1994. Report of national, regional, district
and unit mortality rates. Solihull: West Midlands
Perinatal Audit, 1996.
5. Regional
Director of Public Health. Partners in health.
Birmingham: West Midlands Regional Health Authority,
1992:21-35. (Public health report.)
Government
should meet commitment made in white paper
EDITOR The
systematic review by McDonagh et al confirmed that
fluoridation of the water supplies is effective in
reducing dental caries and has no detrimental
effects on public health.1 It is now time for the
government to meet its commitment made in the white
paper Saving Lives: Our Healthier Nation, published
in July 2000, to require water companies to
fluoridate where there is strong local support for
doing so.
The method used,
however, limits the information that should be
considered by health and local authorities when
deciding whether or not to implement this important
pubic health measure. The stringent criteria used to
measure effectiveness failed to evaluate the full
benefits. The benefits of fluoridation are
cumulative over a lifetime for those who consume
fluoridated water over that period.2 To ignore the
evidence of value to the adult population
underestimates the true impact of the public health
measure.
The only adverse
effect that the review discovered was that of
cosmetically unacceptable fluorosis. The estimates
of the prevalences of cosmetically unacceptable
fluorosis, while based on the international
literature, appear too high for the situation in the
United Kingdom. For example, the estimate of 10% of
the population in fluoridated communities suffering
from cosmetically unacceptable fluorosis runs
against best current evidence for this country,
which suggests that this affects only 3%.3
Those who will be
called on to make decisions on this very important
matter deserve to have the full picture,
particularly as it is relevant to this country, on
which to decide.
P J Holloway,
emeritus professor.
Turner Dental
School, University of Manchester, Manchester M15 1FH
Competing
interests: None declared.
1. McDonagh MS,
Whiting PF, Wilson PM, Sutton AJ, Chestnutt I,
Cooper J, et al. Systematic review of water
fluoridation. BMJ 2000; 321: 855-859[Abstract/Full
Text]. (7 October.)
2. Thomas FD,
Kassab JY. Fluoridation in Anglesey: a clinical
study of dental caries in mothers at term. Brit Dent
J 1992; 181: 36-140.
3. Tabari ED,
Ellwood R, Rugg-Gunn AJ, Evans DJ, Davies RM. Dental
fluorosis in permanent incisor teeth in relation to
water fluoridation, social deprivation and
toothpaste use in infancy. Brit Dent J 2000; 189:
216-220[Medline].
Authors' reply
EDITOR Our study
was a review of primary studies; hence the
meta-analysis by Jones et al was not cited. We were
aware of their work, however, and did screen the six
studies included in their analysis and not in ours.
We excluded these studies because they did not meet
our inclusion criteria. Both Connett and Gibson
comment on our lack of describing fluorosis as an
indication of a toxic effect of fluoride. In fact in
our analysis, fluorosis is considered an individual
negative outcome, as is, for example, bone fracture
or cancer. Regarding Connett's comment about the
lack of consideration of thyroid and pineal studies,
we emphasise that any study meeting inclusion
criteria was included (as were two thyroid studies).
Animal studies were excluded because they provide
less reliable estimates of effect and where human
data are available we think these should not bear
significant weight on decisions about interventions.
Connett also indicates that we have misrepresented a
study by Li et al.1 Our analysis of bone fracture
relates to water fluoridation levels close to 1 ppm
(the relevant concentration for artificial
fluoridation). At 1 ppm, the risk of fracture found
by Li et al was not increased.
We agree with
Holloway that the effect of fluoridation should be
examined over time, which is one reason we excluded
cross sectional studies of positive effects. We did
not exclude studies of adults, but only one met the
inclusion criteria. Holloway further states that our
estimates of fluorosis seem too high for the United
Kingdom. The advantage of a systematic review is to
bring together as much evidence as possible to get a
clearer picture of the true effect. Rather than
depend on a single study, we have more confidence in
the pooled studies. In the meta-regression analysis,
geographical location was not found to be
significantly associated with fluorosis; neither
were other geographically specific variables such as
temperature and altitude.
Gibson, one of our
advisory panel members, comments that delayed
eruption of teeth potentially caused by fluoridation
was ignored. This issue was not ignored in our
review, but we found only one study that met
inclusion criteria. This is an area that may merit
further research. Counter to what Gibson writes, the
Schatz study of neonatal death was indeed included
in our review, and was commented on in our full
report.2 Our review of water fluoridation is
specific and appropriately narrow in focus. It is
not the answer to the question of whether or not to
fluoridate. Our review found a benefit in the form
of reduction in caries, balanced against a dose
related increase in fluorosis. We said that no clear
evidence of other potential negative effects was
found. We have been assiduous in our paper, our full
report, and our contacts with the media, not to
convey a message of no evidence of harm. We suggest
caution against overinterpretation of our results
and emphasise again that the quality of these data
on benefit and harm is only low to moderate.
Marian S McDonagh,
research fellow.
NHS Centre for
Reviews and Dissemination
Jos Kleijnen,
professor.
NHS Centre for
Reviews and Dissemination,University of York, York
YO10 5BB
Competing
interests: None declared.
1. Li Y, Liang C,
Siemenda C, Ji R, Sun S, Gao J, et al. Effect of
long term exposure to fluoridation in drinking water
on risks of bone fractures. 1999. (Unpublished
report, submitted by author.)
2. NHS Centre for
Reviews and Dissemination. A systematic review of
public water fluoridation. York: University of York,
2000. (Report 18.)
Results should
be viewed with concern rather than applause
EDITOR Phipps et al
state that a 95% confidence interval on relative
risk for wrist fracture of 1.00-1.71 due to
community water fluoridation is not significant and
surmise that it may be one of the most cost
effective methods for reducing the incidence of
fractures related to osteoporosis, on the basis of
reduced spine and hip fracture after adjustment for
a dozen factors in addition to age.1 These are
specific to bone mass density, and the changes in
bone mass density in table 3 (due to and correlated
with fluoride exposure) are congruent with changes
associated with fluoride treatment.2-4 In the 1994
guidelines of the Food and Drugs Administration
(published in 1997) for preclinical and clinical
evaluation of agents used in preventing or treating
postmenopausal osteoporosis, the relation between
increased bone mass density and reduced fracture
risk has been validated for patients receiving
oestrogens, but not fluoride. It is now recommended
that clinical trials be restricted to the axial
skeleton only, provided that the patient has good
peripheral bone density, renal function, and vitamin
D status, factors not considered in the multivariate
analysis of Phipps et al. Thus, the analysis is not
entirely cogent regarding fracture. Rather, the two
most significant trends for age adjusted only with
continuous exposure in figure 5 are again increased
wrist fracture (P=0.012) and maybe some decrease in
spine fracture (P=0.079).
The benefit (if
any) to the vertebra from increased bone mass is now
recognised to be at the expense of increased risk of
fracture to the parts of the skeleton that are
subject to forces other than compressive loading.
The new bone formed is weak and structurally
abnormal because of fluoride's alteration of the
normal remodelling process (FDA Consumer, April
1991), and this decrease in quality and strength
presents both clinically and experimentally (with
and without calcium supplementation). This
osteogenic effect occurs at plasma fluoride
concentrations associated with fluoridated areas,
with total accumulation being directly proportional
to total lifetime ingestion (unless exacerbated by
the onset of chronic renal insufficiency). The net
dosage increment associated with the age and weight
adjusted increase in five year relative fracture
risk comparing 1 mg/l with 4 mg/l fluoride in
drinking water is commensurate with 20 years of
community water fluoridation and clinical experience
has taught that denser bones are not necessarily
better bones. 4 5 Thus the 20 year changes in bone
mass density reported by Phipps et al should be
viewed with some concern rather than applause.
T C Schmidt,
director.
Clairemont Town
Council, San Diego, CA 92117-4038, USA
thomas.c.schmidt@lmco.com
Competing
interests: None declared. TCS agrees with Douglas
Carnall (BMJ 2000;321:904) that those who wish to
take fluoride should get it from toothpaste rather
than the water supply.
1. Phipps KR,
Orwoll ES, Mason JD, Cauley JA. Community water
fluoridation, bone mineral density, and fractures:
prospective study of effects in older women. BMJ
2000; 321: 860-864[Abstract/Full Text]. (7 October.)
2. Bauer DC,
Browner WS, Cauley JA, Orwoll ES, Scott JC, Black
DM, et al. Factors associated with appendicular bone
mass in older women. The Study of Osteoporotic
Fractures Research Group. Ann Intern Med 1993; 118:
657-665[Medline].
3. Riggs BL,
Hodgson SF, O'Fallon WM, Chao EY, Wahner HW, Muhs JM,
et al. Effect of fluoride treatment on the fracture
rate in postmenopausal women with osteoporosis. N
Engl J Med 1990; 322: 802-809[Abstract].
4. Dequeker J,
Declerck K. Fluor(ide) in the treatment of
osteoporosis. An overview of thirty years clinical
research. Schweiz Med Wochenschr 1993; 123:
2228-2234[Medline].
5. Sowers MF, Clark
MK, Jannausch ML, Wallace RB. A prospective study of
bone mineral content and fracture in communities
with different fluoride exposure. Am J Epidemiol
1991; 133: 649-660[Abstract].
Authors' reply
EDITOR Connett
voiced his concern about our interpretation of
fracture risk associated with long term exposure to
community water fluoridation. After adjusting for
known confounders, we found a slight, yet
significant reduction in the risk of fracture of the
hip and spine and a trend towards an increased risk
of fracture of the wrist. Following standard
statistical convention, we reported that the
increase in the risk of wrist fracture was not
significant because the 95% confidence interval
included 1.0.
The decrease in the
risk of fractures in both spine and hip outweighs
the trend towards increased wrist fracture.
Fractures of the hip account for the major burden of
osteoporosis and can result in admission to nursing
homes and death. Wrist fractures, however, tend to
occur in healthy more active women and do not have
the economic or social burden associated with hip
fractures.1 Our conclusion that long term exposure
to fluoridated drinking water does not increase the
risk of fracture is also based on the fact that we
saw no association when we evaluated all
non-vertebral fractures (odds ratio 0.96, 95%
confidence interval 0.83 to 1.10). Connett also
refers to the fact that the fluoridation review of
the University of York quotes our confidence
interval for wrist fractures as 1.02 to 1.71. For
their review, the York team used our draft results
that were not fully adjusted for the known risk
factors for fracture.
Schmidt focuses on
the changes we found in bone mineral density and the
association between bone mass density and fracture
risk. He says that denser bones are not necessarily
better bones. We disagree with this statement and
cite the alendronate and raloxifene clinical trials
as prime examples. These trials found that
individuals taking raloxifene and alendronate had
increased spinal bone mass density along with a
decrease in vertebral fracture risk. 2 3 In
addition, trials testing time released or low dose
fluoride for the treatment of osteoporosis also
found both increased spinal bone mass density and
fewer vertebral fractures. 4 5 On the basis of the
increasing literature documenting a significant
correlation between increased bone mass density and
reduced fracture risk, we stand by our claim that
community water fluoridation does not increase the
risk of osteoporotic fractures in older women and
may actually slightly reduce the risk of hip and
vertebral fractures.
Kathy Phipps,
associate professor.
Eric Orwoll,
professor of medicine.
Jill Mason,
associate professor.
Oregon Health
Sciences University, Portland, OR 97201, USA
Jane Cauley,
associate professor of epidemiology.
University of
Pittsburgh, Pittsburgh, PA 15261, USA
Competing
interests: None declared.
1. Kelsey JL,
Browner WS, Seeley DG, Nevitt MC, Cummings SR. Risk
factors for fractures of the distal forearm and
proximal humerus. The Study of Osteoporotic
Fractures Research Group. Am J Epidemiol 1992; 135:
477-489[Abstract].
2. Hochberg MC,
Ross PD, Black D, Cummings SR, Genant HK, Nevitt MC,
et al. Larger increases in bone mineral density
during alendronate therapy are associated with a
lower risk of new vertebral fractures in women with
postmenopausal osteoporosis. Fracture Intervention
Trial Research Group. Arthritis Rheum 1999; 42:
1246-1254[Medline].
3. Ettinger B,
Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T,
Genant HK, et al. Reduction of vertebral fracture
risk in postmenopausal women with osteoporosis
treated with raloxifene: results from a 3-year
randomized clinical trial. Multiple Outcomes of
Raloxifene Evaluation (MORE) Investigators. JAMA
1999; 282: 637-645[Medline].
4. Reginster JY,
Meumans L, Zegels B, Rovati LC, Minne HW, Giacovelli
G, et al. The effect of sodium monofluorophosphate
plus calcium on vertebral fracture rate in
postmenopausal women with moderate osteoporosis. A
randomized, controlled trial. Ann Intern Med 1998;
129: 1-8[Medline].
5. Pak CY, Adams-Huet
B, Sakhaee K, Bell NH, Licata A, Johnston C, et al.
Comparison of nonrandomized trials with slow-release
sodium fluoride with a randomized placebo-controlled
trial in postmenopausal osteoporosis. J Bone Miner
Res 1996; 11: 160-168[Medline].
Little is known
about the safety of fluoridation
EDITOR Your
comments in "This week in the BMJ" and the editorial
by Hausen treated the study by Phipps et al on
community water fluoridation, bone mineral density,
and fractures, which you published alongside the
systematic review of water fluoridation by McDonagh
et al, as introducing new evidence that should
alleviate remaining concerns about the safety of
fluoridation.1-3 The paper by Phipps et al, which
seemed to show a slightly lower risk of fractures,
had been fully accounted for in the systematic
review by McDonagh et al, where it achieved the
lowest rating (high risk of bias), in common with
all but one of the studies on bone problems in the
world literature. It is therefore premature to
suggest that we know all the answers about fluoride
and bones, let alone about the safety of
fluoridation overall.
Baldwin of Bewdley.
House of Lords,
London SW1A OPW edward@baldwin.dircon.co.uk
Competing
interests: None declared. BB holds the honorary
position of vice president of the National Pure
Water Association
1. Hausen HW.
Fluoridation, fractures, and teeth. BMJ 2000; 321:
844-845[Full Text]. (7 October.)
2. Phipps KR,
Orwoll ES, Mason JD, Cauley JA. Community water
fluoridation, bone mineral density, and fractures:
prospective study of effects in older women. BMJ
2000; 321: 860-864[Abstract/Full Text]. (7 October.)
3. McDonagh MS,
Whiting PF, Wilson PM, Sutton AJ, Chestnutt I,
Cooper J, et al. Systematic review of water
fluoridation. BMJ 2000; 321: 855-859[Abstract/Full
Text]. (7 October.)
Ireland has less
decay in non-fluoridated communities
EDITOR I share
Carnall's views on fluoridation.1 The Republic of
Ireland has 73% water fluoridation. So what is its
dental experience? In the most recent figures
published by the World Health Organization for tooth
decay in Ireland, the country lies in only sixth
place for tooth quality.2 Of the five countries with
better teeth, four do not fluoridate and the United
Kingdom has only 10% fluoridation. In Ireland there
are more decay free teeth in non-fluoridated
communities.3
Fifty per cent of
our population has dental fluorosis. I see patients
daily in my surgery who are damaged by fluoride.
They do not smile, they are teased at school, and
they are traumatised by having "rotten" teeth. Is it
an acceptable cost-benefit payoff to cause a dental
disease in half of the population to reduce tooth
decay by a supposed 15%? The idea of mass medicating
an entire population is inherently flawed. When I
prescribe drugs I do so with the knowledge of the
patient's age, weight, and medical history. Water
fluoridation is prescribed by thirst. The more you
drink the more you get. Is this science?
Don Mac Auley,
dental surgeon.
Navan, County
Meath, Republic of Ireland dentist@esatclear.ie
1. Carnall D.
Website of the week: Water fluoridation. BMJ 2000;
321: 904[Full Text]. (7 October.)
2. Marthaler T. M.
The prevalence of dental caries in Europe 1990-1995.
Caries Res 1996; 30: 237-255[Medline].
3. WHO Oral Health
Country/Area Profile Programme. Ireland. Oral
disease prevalence. Available at:
www.whocollab.od.mah.se/euro/ireland/data/irelandcar.html;
accessed 6 June 2001.
© BMJ 2001
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