AARP and the photographers of Magnum Photos look at older people living in new ways around the world in A New Age.

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Nat'l Kidney Foundation Bullied and Threatened Into Rewording Fluoridation Endorsement

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651241 - This false claim has already been addressed by David 08-17-2018 09:44 PM.

 

In 2007, an attorney, Robert Reeves, sent the NKF an unconscionable letter threatening lawsuits against the then current and past members of the NKF Board of Directors, both collectively and against their personal assets, as well as against the NKF staff, if NKF did not remove its name from the list of organizations which support fluoridation.  The  NKF is a charitable organization which provides much needed services and activities on behalf of kidney patients.   Rather than waste its limited resources and subjecting its Boards and staff to protracted and expensive litigation fighting an antifluoridationist attorney with nothing to lose,  the NKF prudently decided to simply remove its name from the list.

https://americanfluoridationsociety.org/wp-content/uploads/2017/03/2007-Letter-from-Attorney-Reeves-...


It is important to note that neither the NKF, nor any other credible organization in the world opposes fluoridation, which the NKF would most certainly do if it deemed fluoridation to be any danger to kidney patients.

 

Since Osmunson and CarryAnne are apparently not able or willing to answer the questions I have asked them several times, perhaps you could take a stab at answering a few of them


~> Q1 If the anti-F claims are actually supported by legitimate scientific evidence, why have you and the other fluoridation opponents (FOs) been completely unsuccessful for 70+ years in changing the scientific consensus that CWF is a safe and effective public health initiative? 

 

~> Q2 What is your opinion of the importance of the scientific consensus in making science and health related decisions – both in general and specifically with respect to CWF? 

 

~> Q3 If you don’t accept the scientific consensus as a legitimate representation of the majority position on relevant issues, what is your alternative explanation and terminology?

 

~> Q4 What is your explanation for the fact that virtually all the major science and health organizations continue to publically recognize the benefits of CWF – and their members & representatives have not mutinied?  


~> Q5 Do you accept as true CarryAnne’s representations of the ADA, EPA and ATA and their members as “[affected by] financial benefit, ignorant, willful blindness, morally corrupt, cowards &/or sociopaths"? (Demand -08-22-2018 06:59 AM), (D-08-19-2018 01:05 PM), (D-07-25-2018 11:30 PM) & (D-07-25-2018 11:30 PM)  Do you believe those are accurate descriptions of all members of the 100+ organizations in the world who either publically recognize the benefits of CWF or have not publically spoken out against it?


~> Q6 Do you accept as true Dr. Osmunson’s Demand-07-09-2018 09:09 PM claim about the CDC, ADA and AAP, “Johnny, the credibility of those so called "scientific" organizations has been seriously tarnished.  They do not protect the public.  They are lemmings, followers, part of a herd, not scientists.  Scientists question and do not assume and base their science on trust”? 
If you accept Dr. Osmunson’s explanation, how would his additional claim “Yes, they are the best in their field and experts, but not in fluoridation”  be even remotely justifiable?


~>  Q7 If the representatives of those health organizations that publically recognize the benefits of fluoridation have not publically denounced CWF, and they have completely ignored &/or misinterpreted the body of evidence you believe proves CWF to be a dangerous practice, and they have followed each other like lemmings, how can any of them possibly be considered the best in their field and experts in any other areas of their practices?


I, for one, find it impossible to imagine that a majority of scientists and health professionals who are committed to carefully evaluating understanding evidence and who are responsible for the health of citizens would ignore or dismiss the accusations of FOs without examining the evidence.

 

~>  Q8 Do you believe Dr. Osmunson’s explanations apply to the other 100+ organizations that do not publically denounce fluoridation and their hundreds of thousands of representatives? These organizations include: The World Health Organization which represents 191 countries, the British Dental Association (around 22,000 members), the British Medical Association (over 156,000 members), the Irish Dental Association (over 1,800 members), the American  Dental Association (over 114,000 members), the American Medical Association (over 200,000 members), the American Academy of Pediatrics (around 64,000 members), the Canadian Dental Association (over 16,000 members), the Canadian Medical Association (80,000 members), The Australian Dental Association (over 11,000 members), the Australian Medical Association (over 28,000 members), the New Zealand Dental Association (2,026 members), and so on… 

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Nat'l Kidney Foundation Drops Fluoridation Endorsement

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The National Kidney Foundation withdrew its support of water fluoridation citing the 2006 National Research Council (NRC) report indicating that all kidney patients, not just those on dialysis, are more susceptible to fluoride’s bone and teeth-damaging effects

.

The kidney-impaired retain more fluoride and risk skeletal fluorosis (an arthritic-type bone disease), fractures and severe enamel fluorosis, which may increase the risk of dental decay, reports the NRC.

 

 

The National Kidney Foundation’s (NKF) former fluoridation position statement also carried surprising cautions.  The NKF advised monitoring children’s fluoride intake along with patients with chronic kidney impairment, those with excessive fluoride intake, and those with prolonged disease.

 

But NKF now admits, "exposure from food and beverages is difficult to monitor, since FDA food labels do not quantify fluoride content."  

 

The NKF’s April 15, 2008 statement goes further: "Individuals with CKD [Chronic Kidney Disease] should be notified of the potential risk of fluoride exposure."

 

"There is consistent evidence that impairment of kidney function results in changes to the way in which fluoride is metabolized and eliminated from the body, resulting in an increased burden of fluoride," concludes Kidney Health Australia. in a paper NKF recommends reading  

 

On June 20, 2008, it was reported that the ADA was forced to finally drop the NKF as a fluoridation supporter

 

However, even the ADA reports in its Fluoridation "Facts" booklet  that "decreased fluoride removal may occur among persons with severely impaired kidney function who may not be on kidney dialysis."

 

Even the CDC has expressed concern about fluoride's adverse effects to those with impaired kidney funciton. http://fluoridedangers.blogspot.com/2014/11/cdc-misleads-legislators-about.html

 

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Re: The scientific consensus continues to support CWF

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RandyJ asks BillO, "If you believe your interpretation of the “evidence” actually supports the conclusion that optimally fluoridated water is obviously and dangerously carcinogenic, why on earth are you presenting this devastating news and “evidence” on a public forum instead of demanding a meeting with members of the American Cancer Society, the Canadian Cancer Society (and other relevant expert organizations) to instruct them on your “correct way” to evaluate the evidence."

 

Response:  Probably because it is easier to convince lay persons and a few conspiracy theorists who have graduated from the University of Google that controversy exists where there is no controversy,  than it would be to convince knowledgeable  people with legitimate scientific training.

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Diet Not Fluoride Prevents Tooth Decay

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Despite 73 years of water fluoridation, a US study finds Food insecurity linked to poor oral health https://t.co/PoQbKAzDsr

In FiJi, dentists see much less decay in poor children because they eat healthy diets in a more remote Fiji island http://www.fijitimes.com/dentists-discover-tooth-decay-trend/

In the 2004 JADA, it was reported that cavities occur in sixty-percent of U.S. preschool children, and more often in the poorly nourished, Plus federal statistics indicate that poor health is closely associated to bad teeth regardless of fluoridation levels.

About 2/3 of Americans drink fluoridated water. But those skipping breakfast and fruits and vegetables still have more cavities, according to researchers, Dye et al.

Because skipped breakfast is associated with higher caloric intake, poor nutrient intake and obesity, Dye and colleagues used "skipped daily breakfast" as an indicator of poor nutrition along with not eating required 5 fruits and vegetables daily.

Over sixty years ago, dental researcher Weston Price in his book "Nutrition and Physical Degeneration" examined various countries' inhabitants and their food choices. He discovered that bad teeth are created by poor diets

In their zeal to promote fluoride, dentistry, ignoring diet, may have helped create a billion-dollar toothpaste industry while enabling an appalling tooth decay national epidemic to fester and grow like the unfilled cavities in Medicaid patients who are often refused dental treatment

In the year 2000, the surgeon general decared tooth decay a national epidemice. Despite millions of dollars poured into fluoridation campaigns, meetings, conferences, etc, the problem persists. In fact, in 2015 Senator Bernie Sanders reported that the dental crisis persists because all Americans don't have access to dental care - https://www.sanders.senate.gov/newsroom/press-releases/dental-crisis-in-america

Americans are fluoride-overdosed and dentist deficient.

Dental care is the largest unmet health need of school age children, according to the American Dental Association (ADA).( "1985 was the year that the ADA stoped funding diet-related caries research, which may reflect a lack of interest but not a lack or an excess of knowledge," according to "Caries Research," (38,S1,04)

Federal statistics support the poor health/more tooth loss association, regardless of fluoridation levels.

Dental crises are occuring in most fluoridated cities http://www.FluorideNews.Blogspot.com

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Re: Fluoride - Demand AARP Take Action

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It seems necessary to discuss what is meant by scientific consensus and better define the difference between "endorsements" and statements of consensual science.

An endorsement is what Tiger Woods might do with respect to some brand of golf-clubs.

Reports of consensual science source are composed by teams of distinguished scientists, panels of experts, who are selected on the basis of their knowledge, professional reputation and experience to look at all facets of scientific issues.  Supported by librarians who collect the pertinent high quality literature, and support staff, the experts debate the evidence and draft a final report and recommendations.   These are large and often expensive undertakings.

Advocacy statements from organizations like the American Academy of Pediatricians (AAP), the American Association of Family Practitioners (AAFP) and the British Medical Association (BMA) are founded upon evidence based science and reflect both the specific expertise of the organization's members and the findings of systematic reviews.

These are but three of prestigious organizations of the approximately 150 that the Canadian National Institute of Public Health lists as supporting fluoridation

Water Fluoridation:  An Analysis of the Health Benefits and Risks
Scientific Advisory
Institut national de santé publique
Quebec , June 2007, p 47
http://www.inspq.qc.ca/pdf/publications/705-WaterFluoration.pdf

All science including for example, theoretical physics, molecular biology, climatology and public health rely on such consensus of legitimate experts.   It is the only reasonable choice anyone has.

Systematic Reviews are at the top of evidence-based information hierarchy and are a most useful place to determine what is the consensus of recognized experts

https://www.researchgate.net/figure/The-traditional-hierarchy-of-evidence-based-medicine-The-higher-...

Harvard science historian Naomi Orestes in a TED talk well explains the fundamental importance of consensus to the scientific endeavor:

http://www.ted.com/talks/naomi_oreskes_why_we_should_believe_in_science#t-29637

With respect to the cancer issue raised, no systematic review has found fluoridation causes cancer.  Many recent systematic reviews could be quoted .  Here's the conclusion from the 2010 European Scientific Committee on Health and Environmental Risks:  "SCHER agrees that epidemiological studies do not indicate a clear link between fluoride in drinking water, and osteosarcoma and cancer in general. There is no evidence from animal studies to support the link, thus fluoride cannot be classified as carcinogenic."

Any single study or series of arguments that may be posted in a public forum like the AARP's are distractions from the real science compared to easily verified expert consensus.

For what it is worth, Hardy Limeback, a dentist like Dr. Osmunson who opposes fluoridation, is unwilling to claim fluoridation is related to cancer.  As you know he was on the National Research Council's Committee on Fluoride in Drinking Water.  Here is Dr. Limeback's statement from a public record submission to the Juneau City Council which was considering fluoridation in 2006.  Dr. Limeback well reflects the complexity of these data and the importance of technical and professional expertise in arriving at consensus.

"I'm not in a position to discuss the cancer data. No one should be critical or supportive of the fluoride and cancer literature without having some experience in epidemiology, toxicology, cancer risk assessment, clinical design and interpretation and years of experience. We had people that fit that description on the NAS committee. If you have any questions about the conclusions of the NAS report, I suggest you contact people who can address your concerns. .."

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The scientific consensus continues to support CWF

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Thank you Dr. Haynie for your succinct response to Dr. Osmunson’s CWF causes cancer claims 09-04-2018 03:14 PM.  He is still avoiding my request that he explain his earlier comments 08-27-2018 01:40 AM, redefining the Scientific Consensus as an “Endorsement Consensus”, claiming 08-19-2018 02:18 AM that “Endorsements are not science”, claiming 07-09-2018 09:09 PM that “Most endorsements are not backed by a good scientific review of all sides of the literature” and making accusations of the CDC, ADA and AAP that, “None reviewed the science. All the so called "scientific" organizations were all puppets of each other with fluoridation.

 

Dr. Osmunson – Let’s look at your statement 09-04-2018 02:04 PM, “Lets talk science rather consensus.  Remember, the masses can be wrong.  Marketing can change public opinion” just before you dumped over 16,000 words into the discussion in an apparent attempt to support your claim that drinking optimally fluoridated water is a significant risk factor for causing cancer.  That was one of the most remarkable examples of Gish Gallop I have ever seen… 

 

If you believe your interpretation of the “evidence” actually supports the conclusion that optimally fluoridated water is obviously and dangerously carcinogenic, why on earth are you presenting this devastating news and “evidence” on a public forum instead of demanding a meeting with members of the American Cancer Society, the Canadian Cancer Society (and other relevant expert organizations) to instruct them on your “correct way” to evaluate the evidence.

 

Following protocols that are even remotely scientific would first and foremost require presenting legitimate scientific evidence to the relevant experts and convincing them that your interpretations are legitimate.  But that’s the whole issue with these anti-F opinions, isn’t it?  Relevant experts have evaluated the evidence you just presented and have not accepted your anti-F conclusions. 

 

In fact, the ACS states, “In 1993, the Subcommittee on Health Effects of Ingested Fluoride of the National Research Council, part of the National Academy of Sciences. … The Subcommittee concluded that none of the data demonstrated an association between fluoridated drinking water and cancer” and “A 1999 report by the CDC supported these findings. The CDC report concluded that studies to date have produced “no credible evidence” of an association between fluoridated drinking water and an increased risk for cancer” and “In 2011, researchers examined the possible relationship between fluoride exposure and osteosarcoma in a new way. … The analysis showed no difference in bone fluoride levels between people with osteosarcoma and people in a control group who had other malignant bone tumors.” and “More recent population-based studies using cancer registry data found no evidence of an association between fluoride in drinking water and the risk of osteosarcoma or Ewing sarcoma.”

 https://www.cancer.gov/about-cancer/causes-prevention/risk/myths/fluoridated-water-fact-sheet#r6

 

The CCS publically states, “Based on current evidence, CCS believes it is unlikely that adding fluoride to water raises the risk of cancer, including osteosarcoma, in humans. At the same time, we know that there are many benefits to water fluoridation, especially for people who have less access to dental care. We will continue to watch this area of research and update our information as we learn more.”

http://www.cancer.ca/en/prevention-and-screening/reduce-cancer-risk/make-informed-decisions/know-you...

 

Does the fact that neither of these organizations supports your outlier interpretation of the cancer-related evidence mean that you extend your 07-09-2018 09:09 PM accusations of the CDC, ADA and AAP to the ACS and CCS? 

 

That libelous claim reads in part, the “CDC references the ADA and AAP,  and the ADA and AAP reference each other and the CDC.  Circular referencing.”, and “the credibility of those so called 'scientific' organizations has been seriously tarnished.  They do not protect the public.  They are lemmings, followers, part of a herd, not scientists.  Scientists question and do not assume and base their science on trust”, and “Yes, they are the best in their field and experts, but not in fluoridation“.

 

So, do you believe members of the ACS and CCS are "the best in their fields", but they can’t get it right when evaluating the carcinogenic risks of community water fluoridation (CWF) - Really?

You still have not addressed my questions about the necessity of the scientific consensus to protect the public from rampant fear-mongering by anti-science activists (ASAs).

Actually, challenging the current Scientific Consensus (or Expert Consensus) with new, legitimate evidence is a critical element of the scientific method.

Naomi Oreskes: Why we should trust scientists:

https://www.youtube.com/watch?v=RxyQNEVOElU
https://vialogue.wordpress.com/2014/06/26/ted-naomi-oreskes-why-we-should-trust-scientists/

 

Nor have you provided a rational explanation (besides claiming everyone who disagrees with you is a lemming) to explain why only a small group of outlier, alternative health organizations support the anti-F opinions – in contrast to all major science and health organizations (and their members) that either publically recognize the benefits of CWF or have not made public statements that CWF is a harmful public health measure.

 

Nor have you provided a logical alternative to replace accepting the scientific consensus when the public is evaluating complex, scientific conclusions.  Unfortunately two of your claims are true, “Marketing can change public opinion

 

Nor have you provided a logical alternative to replace accepting the scientific consensus when the public is evaluating complex, scientific conclusions.  Unfortunately two of your claims are true, “Marketing can change public opinion – ASAs simply throw out masses of fear-laced misinformation and misdirection and try to scare the public into trusting their conclusions, and because of that mistaken trust, “the masses can be wrong“, which reminds me of Kaa's attempt to hypnotize Mowgli into trusting him. 

https://www.youtube.com/watch?v=vDs57R6MYsY

 

Randy Johnson

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Re: Fluoride and Cancer

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Message 857 of 1,372

BillO, 

 

We must consider the fact that there have been over 4000 studies on fluoride alone.  Some studies are peer-reviewed, some studies have been debunked.

 

It is odd isn't it.  When one looks at the discussion presented by the American Cancer Society on water fluoridation, ( https://www.cancer.org/cancer/cancer-causes/water-fluoridation-and-cancer-risk.html ) one would think water fluoridation does not lead to any kind of cancer.  In the studies the ACS presents there is either No Evidence, (For example:  "In 2011, the state of California’s Carcinogen Identification Committee (CIC) reviewed the evidence and concluded that “fluoride and its salts has not been clearly shown to cause cancer.”), or there is No Strong Evidence for any link between the two.  

 

On the other hand, when one looks at your cherry-picked non-peer reviewed studies, one would think that osteosarcoma and other forms of bone cancer are almost a certainty.

 

Considering the fact that there are roughly 400 cases of the bone cancer, osteosarcoma, per year in the U.S., and considering the fact that hundreds of millions of people enjoy the health benefits of optimally fluoridated water on a daily basis, you would think, according to your cherry-picked studies, that hospitals would be over-run with these bone-cancer victims.  But they aren't are they.

 

The American Cancer does not accept funding from unethical alternative health businesses which routinely receive warning letters from the FDA.  Fluoride Alert, & the Fluoride Action Network do.  The sole existence of the American Cancer Society does not depend on the creation of some controversy, where no controversy actually exists.  The existence of Fluoridealert does. 

 

Perhaps that is why we see such different interpretations between the American Cancer Society & Fluoridealert when it comes to water fluoridation and cancer. 

 

Dr. Bill, have you ever had any relationship with the Fluroide Action Network? 

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Re: Fluoride and Cancer

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Procter and Gamble:

Procter & Gamble, releases the findings of its own rat study of fluoride and cancer they conducted between 1981-1983.  While Procter and Gamble’s study finds several bone tumors in the fluoride-treated animals (versus none in the controls), the results do not achieve statistical significance and Proctor & Gamble’s scientists dismiss them as random. According to the published report:

“All bone neoplasms were considered to be incidental and spontaneous and not related to fluoride treatment, because of their low incidence and random distribution”[10]

In 1991, the FDA publishes a review of Procter & Gamble’s rat study. The FDA identifies two additional osteosarcomas in the fluoride-treated rats which were not identified in Procter & Gamble’s published report. The FDA states:

“The adequacy of the gross examination at necropsy was questioned based upon the rat tumors that were not identified by the contract (Procter & Gamble) laboratory” (FDA 1991).

The FDA notes that the incidence of bone tumors in the Procter & Gamble study still do not achieve statistical significance. The FDA thereby concurs with Procter & Gamble that the bone tumors are incidental.

Contributes to Osteomas: Maurer 1993, the FDA also reviews Procter & Gamble’s mouse study.  Among both sexes of the fluoride-treated mice, there is a significant, dosedependent increase in osteomas, although no osteosarcomas. The occurrence of the osteomas is believed to be related to the presence of a virus in the mice; however, the FDA finds:

“Active virus was found in the osteomas but not in animals that did not have osteomas. It is clear, nonetheless, that if [the virus] had a role it was only in the presence of fluoride.”

Known Osteosarcoma Association: Cohn 1992.  The New Jersey Department of

Health conducts a study of osteosarcoma occurrence in Central New Jersey,  “An Epidemiologic Report on Drinking Water and Fluoridation.” The study finds a statistically significant relationship between fluoridation and osteosarcoma among males less than 20 years old: 

“Recently, a national study of drinking water fluoridation at the country level found a significant association with osteosarcoma incidence among males under 20 years of age (Hoover et al., 1991). However, the meaning of the association was questioned by the authors because of the absence of a linear trend of association with the duration of time for which the water supplies were fluoridated… As a follow-up to the study by Hoover et al., a small study of similar design was initiated by the New Jersey Department of Health to compare drinking water fluoridation at the municipal level with the municipal residence of osteosarcoma cases at the time of diagnosis… The study observed an association between fluoridation of water and osteosarcomas among males under 20 years of age in seven Central New Jersey counties.”

 

Known Carcinogenic: Lee[1] 1993 Reported 6.9 times higher osteosarcoma incidence for males aged 10-19 years old when comparing fluoridated and non-fluoridated seven counties in the central New Jersey area.

Known Carcinogenic: Yiamouyiannis, 1993, analyzes the National Cancer Institute’s data in addition to two other databases containing fluoride exposure/ osteosarcoma information. Like NCI’s investigators (Hoover 1991), Yiamouyiannis finds osteosarcoma rates to be higher among young males under 20 in fluoridated versus unfluoridated areas. To quote:

“Recent studies showing substantial increases in the incidence of bone cancer and osteosarcoma in males (but not females) exposed to fluoride gave us the unique opportunity of using females as a control group to determine whether there is a link between fluoridation and bone cancer in males. Using three different data bases, we found that 

  • the bone cancer incidence rate was as much as 0.95 cases a year per 100,000 population higher in males under age 20 living in fluoridated areas;
  • the osteosarcoma incidence rate was 0.85 new cases a year per 100,000 population higher in males under age 20 living in fluoridated areas; and
  • for males of all ages, the bone cancer death rate and bone cancer incidence rate was as much as 0.23 and 0.44 cases higher per 100,000 population, respectively, in fluoridated areas. These findings indicate that fluoridation is linked to an increase in bone cancer and deaths from bone cancer in human populations among males under age 20 and that this increase in bone cancer is probably all due to an increase in osteosarcoma caused by fluoride.”

Genotoxic Mihashi 1996 report fluoride is genotoxic to rat bone. The authors note that the fluoride-induced genotoxicity in bone reinforce the biologic plausibility of a fluorideosteosarcoma connection. The authors used the same type of rat (F344/N) used in NTP’s cancer bioassay.

“Because the origin of osteosarcoma is considered to be osteoblastic/osteogenic cells, the ability of sodium fluoride to induce chromosome aberrations in these cells provides a mechanistic basis for the occurrence of osteosarcomas observed in sodium fluoride treated animals in the NTP study. Ingested fluoride is accumulated in bone, suggesting that osteoblastic/osteogenic cells in the bone microenvironment can be exposed to high levels of fluoride during bone formation. Our data and the NTP findings provide evidence that bone can be an organ for NaF carcinogenesis.”[2]

 

Gandhi (2017)[3] “Oxidative stress is reported to negatively affect osteoblast cells. Present study reports oxidative and inflammatory signatures in fluoride-exposed human osteosarcoma (HOS) cells, and their possible association with the genes involved in osteoblastic differentiation and bone development pathways. HOS cells were challenged with sublethal concentration (8 mg/L) of sodium fluoride for 30 days and analyzed for transcriptomic expression. In total, 2632 transcripts associated with several biological processes were found to be differentially expressed. Specifically, genes involved in oxidative stress, inflammation, osteoblastic differentiation, and bone development pathways were found to be significantly altered. Variation in expression of key genes involved in the abovementioned pathways was validated through qPCR. Expression of serum amyloid A1 protein, a key regulator of stress and inflammatory pathways, was validated through western blot analysis. This study provides evidence that chronic oxidative and inflammatory stress may be associated with the fluoride-induced impediment in osteoblast differentiation and bone development.” 

 Note: Although the 8 mg/L Gandhi used is sublethal, it is much higher than blood concentrations but not out of range for bone fluoride concentrations which can reach higher, over 800 ppm.   Gandhi (2017) appears to dovetail with Wei (2014) below.

Wei (2014)[4] Chronic excessive fluoride intake may cause fluorosis, which chiefly manifests as bone damage (or skeletal fluorosis). However, the molecular mechanism of skeletal fluorosis has not been clarified up to the present. The objective of this study was to analyze the effects of fluoride treatment on two of bone morphogenetic protein family member (BMP-2 and BMP-3) expression and cell viability using human osteosarcoma MG-63 cells as a model. Sodium fluoride (NaF) had pro-proliferation effects at relatively moderate concentration, with 5 × 10(3) μmol/L having the best effects. At 2 × 10(4) μmol/L, NaF inhibits cell proliferation. BMP-2 and BMP-3 expression was significantly induced by 5 × 10(3) μmol/L NaF and, to lesser extent, by 2 × 10(4) μmol/L NaF. Correspondingly, mothers against decapentaplegic homolog 1 (Smad-1) increased at both doses of NaF, which indicated the BMP signaling pathway was activated. Notable increases in secreted alkaline phosphatase (ALP) were observed when cells were treated with 5 × 10(3) μmol/L NaF. A BMP specific inhibitor LDN193189 suppressed cell proliferation induced by 5 × 10(3) μmol/L NaF. Also, 2 × 10(4) μmol/L NaF induced apoptosis but likely through a mechanism unrelated to the BMP pathway. Collectively, data show that NaF had dose-dependent effects on cell proliferation as well as BMP-2 and BMP-3 expression in MG-63 cells and suggested that cell proliferation enhanced by NaF-induced BMP members may be a molecular mechanism underlying skeletal fluorosis.

Note: Wei (2014) reported specific effects at 5 × 10(3) μmol/L NaF, which is 9.5 mg/L (ppm), close to Gandhi’s 8 ppm.  

Sandhu (2011)[5]The present study was planned to analyze serum fluoride, sialic acid, calcium, phosphorus, and alkaline phosphatase levels in 25 patients of osteosarcoma and age- and sex-matched subjects with bone-forming tumours other than osteosarcoma and musculo-skeletal pain (controls, 25 each). . . Mean serum fluoride concentration was found to be significantly higher in patients with osteosarcoma as compared to the other two groups. The mean value of flouride in patients with other bone-forming tumors was approximately 50% of the group of osteosarcoma; however, it was significantly higher when compared with patients of group I. Serum sialic acid concentration was found to be significantly raised in patients with osteosarcoma as well as in the group with other bone-forming tumors as compared to the group of controls. There was, however, no significant difference in the group of patients of osteosarcoma when compared with group of patients with other bone-forming tumors. These results showing higher level of fluoride with osteosarcoma compared to others suggesting a role of fluoride in the disease.”

Huo (2013)[6] [Saos-2 cells are osteosarcoma cells] “We found that fluoride enhanced the proliferation of Saos-2 cells in a dose-dependent manner and 0.2 mM of fluoride resulted in a higher expression of osteoblast marker genes. In addition, immunofluorescence analysis showed that the promotion effects of 0.2 mM of fluoride on Saos-2 cells differentiation were associated with the activation of the BMP/Smad pathway.”

Huo (2013) Figure 1. “Growth curve of fluoride-treated Saos-2 cells. Saos-2 cells were seeded into 96-well plates and cultured with different concentrations of NaF for 24, 48, and 72 h as indicated in the “Materials and Methods.” The WST assay was performed to quantify the cytotoxicity of fluoride to Saos-2 cells. Asterisk indicate the significant differences.”

 

 

 

Huo (2013) Fig. 3

Content of Smad1 and p-Smad1/5 protein in fluoride-treated Saos-2 cells. Laser scanning confocal microscopy was used to detect expression of Smad1 and p-Smad1/5 proteins after exposure to NaF (200×). a, c Control (0 mM NaF) and b, d 0.2 mM NaF groups; a, b Smad1 and c, d p-Smad1/5. Three wells were assayed for each experimental treatment, and three separate experiments were performed

Note:  For comparison, 0.2 mM x 1,000 μmol/mM = 200 μmol X o.oo19 μmol/L NaF = 0.38 mg/L (ppm) sodium fluoride.

 

[1] Lee JR Fluoridation and Bone Cancer, Fluoride, Vol.26. No.2 1993   Accessed 4/25/2015 http://www.fluorideresearch.org/262/files/ FJ1993_v26_n2_p079-164.pdf

[2] (Mihashi M, Tsutsui T. (1996). Clastogenic activity of sodium fluoride to rat vertebral body-derived cells in culture. Mutation Research 368(1):7-13. May.)

[3] Gandhi D, Naoghare PK, Bafana A, Kannan K, Sivanesan S .Biol Trace Elem Res. Fluoride-Induced Oxidative and Inflammatory Stress in Osteosarcoma Cells: Does It Affect Bone Development Pathway?  2017 Jan;175(1):103-111. doi: 10.1007/s12011-016-0756-6. Epub 2016 May 28.

 

[4] Wei Y1, Wu Y, Zeng B, Zhang H.  Effects of sodium fluoride treatment in vitro on cell proliferation, BMP-2 and BMP-3 expression in human osteosarcoma MG-63 cells. Biol Trace Elem Res. 2014 Dec;162(1-3):18-25. doi: 10.1007/s12011-014-0148-8. Epub 2014 Oct 14.

[5] Sandhu R1, Lal H, Kundu ZS, Kharb S.  Serum fluoride and sialic acid levels in osteosarcoma. Biol Trace Elem Res. 2011 Dec;144(1-3):1-5. doi: 10.1007/s12011-009-8382-1. Epub 2009 Apr 24.

 

 

[6] Huo L1, Liu K, Pei J, Yang Y, Ye Y, Liu Y, Sun J, Han H, Xu W, Gao Y. Fluoride promotes viability and differentiation of osteoblast-like Saos-2 cells via BMP/Smads signaling pathway. Biol Trace Elem Res. 2013 Oct;155(1):142-9. doi: 10.1007/s12011-013-9770-0. Epub 2013 Aug 7.

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Re: Fluoride and Cancer

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  1. Concerns with NTP Review of Carcinogenicity of Fluoride

Despite criticism, the NTP maintains their assessment of “equivocal evidence.” In 1991, NTP scientists publish a paper which concludes:

“The current findings are weakly supportive of an association between sodium fluoride administration and the occurrence of osteosarcomas in male rats, but are not conclusive… [I]n view of the widespread exposure of the population to fluorides from a variety of sources it would appear prudent to re-examine previous animal and human epidemiologic studies, and perform further studies as needed to evaluate more fully any possible association between exposure to fluorides and the occurrence of osteosarcomas of bone.”[1]       

            NTP review comments on page 10, include:

  1. “Dr. Ashby, the second principal reviewer, agreed with the conclusions. However, he considered the definition for equivocal evidence of carcinogenic activity to be insufficiently precise for male rates. . . .” He suggested: “Taken together the current findings are inconclusive, but are weakly supportive of an association between sodium fluoride administration and the occurrence of osteosarcomas in male rats.”
  2. Silbergeld, “pointed out that the doses used were not orders of magnitude above human exposure levels. She supported further research on genotoxicity and on mechanisms of sex differences seen.”
  3. Gold noted that this was an unusual study in that there was not a zero control group.”
  4. “There was discussion by Dr. McKnight with Dr. J. Haseman, NIEHS, as to why data from paired (age-matched) controls were not used in primary data tables.
  5. Zeise “reiterated the need expressed by other Panel members for designing another study with higher top doses. Dr. Zeise noted that the fluoride concentrations in high-dose rats were within the range observed in humans and the differences in pharmacokinetics and deposition of fluoride in bone between humans and animals should be studied.”
  6. Yiamouyiannis said, “a dose-dependent relationship between fluoride and the number of male rats with oral squamous cell tumors and a dose-dependent relationship between oral squamous cell metaplasia dn tumors in female rats along with the increased incidence of osteosarcomas in male rats supported a finding of clear evidence of carcinogenic activity of fluoride in rats.”
  7. Those representing dentists and industry objected to the conclusions.

             

When fluoride damages DNA, is the damaged DNA make the offspring more

susceptible to cancer?   With the current research, objection to the NTP study should also be made to the lack of a “life-time” exposure from preconception with parents, throughout life of the offspring.   Starting the rats and mice at 5 and 4 weeks of age in the NTP study, did not demonstrate the effects of the fluoride on sperm, egg, fetus, and during a major growth period of their early lives. 

Downgrading by NTP of non-bone tumors (liver, oral, and thyroid) found with increased incidence among the fluoride-treated animals is controversial.  

Concerns with NTP study:  The journal Chemical & Engineering News reports:

“A number of other government officials who asked not to be identified also have told C&EN that they have concerns about the conclusions of the NTP study. They, too, believe that fluoride should have been placed in the “some evidence” category, in part because osteosarcoma is a very rare form of cancer in rodents.”

Cancer diagnosis upheld:    Battelle’s diagnosis of hepatocholangiocarcinoma was upheld by the scientist (Dr. Melvin Reuber) who first identified hepatocholangiocarcinoma as a distinct cancer. As noted by EPA toxicologist Dr. William Marcus:

“Melvin Reuber, M.D., a board certified pathologist and former consultant to EPA and part time EPA employee, reviewed some of [the] pathology slides and the Batelle report. . . . [Reuber] first published the work that identified hepatochangiocarcinoma as a pathologic entity. . . . Dr. Reuber reviewed the pathology slides and stated that these lesions are indeed hepatocholangiocarcinoma.”[2]

Despite Reuber’s concurrence, the NTP ultimately downgraded the hepatocholangiocarcinoma finding. The NTP did so through a two-step process. First, NTP’s “Quality Assurance” pathogist reclassified them as hepatoblastomas (another form of liver cancer). Then, while conducting their statistical analysis, NTP reclassified the hepatoblastomas as hepatocarcinomas – a more common form of tumor. Because there was no significant increase in hepatocarcinomas among the fluoride-treated animals, the NTP concluded that there was no effect.

            The NTP has issued the following statements about this analysis:

“During the pathology review procedures several of the tumors diagnosed originally as hepatocholangiocarcinomas were considered more apppropriately callled hepatoblastomas.”[3]

“The study pathologist (Battelle) diagnosed hepatocholangiocarcinomas in one special control female, one low dose male, one low dose female, one medium dose male, three high dose males, and three high dose females. The QA (Quality Assurance) pathologist confirmed the presence of these tumors but felt that most of them were more appropriately diagnosed as hepatoblastomas.”[4]

“The incidences of liver neoplasms in all groups of dosed and control male and female mice were higher than incidences previously seen in NTP studies, but did not appear related to chemical treatment. Several hepatoblastomas and hepatocholangiocarcinomas were diagnosed in male and female mice. Hepatoblastoma and hepatocholangiocarcinoma of mice are phenotypic variants of hepatocellular carcinoma with characteristic cell types and morphologic patterns. The hepatoblastomas contained a cell population which resembled embryonal liver cells as well as neoplastic cells characteristic of a typical hepatocellular carcinoma, whereas the hepatocholangiocarcinomas exhibited both hepatocyte and biliary differentiation. As phenotypic variants of hepatocellular carcinoma, the incidences of these neoplasms were combined with the other hepatocellular neoplasms for analysis. The appearance of these phenotypic variants in dosed animals is unusual, and the biologic significance, if any, is unknown.”[5]

Summary of NTP study by LANCET:

“The original study was directed from 1985 to 1987 by Dr John D. Toft II, manager of the pathology section at Battelle Memorial Institute in Columbus, Ohio. The Battelle study’s principal finding was the occurrence of an extremely rare liver cancer, hepatocholangiocarcinoma, in male and female mice. In 1989, the NTP asked Experimental Pathology Laboratories, of Sterling, Virginia, to review Battelle’s data. At this point, the liver cancer finding, along with a diagnosis of metaplastic and precancerous cells in the mouths of rats, was downgraded.

The only effect of fluoride that was left after these reclassifications and still another review by a board of pathologists and others was osteosarcoma. Dr Marcus believes the Battelle diagnosis of liver cancers was sound and should have been included in the NTP report. This, he says, would change “the (NTP) equivocal finding… to at least some evidence or clear evidence of carcinogenicity”.

NTP’s failure to emphasize another finding also figured in Dr Marcus’ critique. Three out of four in-vitro tests, he says, proved fluoride to be mutagenic, “supporting the conclusion that fluoride is a probable human carcinogen”. A careful reader can find this information in the text of the report, but the authors make no mention of these data in their conclusions.”[6]

Summary of NTP study by C&E News: 

“The final report for the study was prepared by the NTP staff, but the testing itself was done by Battelle Columbus Laboratories under contract to NTP. A report prepared by Battelle was audited by a quality assurance contractor, and a separate group of pathologists reviewed the studies. In the process, a number of positive findings in the original Battelle report were downgraded. Slides first diagnosed as showing a rare form of liver cancer called hepatochlolangiocarcinoma were later said to indicate hepatoblastoma, another type of rare malignant lesion, and finally to show the far more common cancer hepatocarcinoma. These hepatocarcinomas were combined with the other hepatocarcinomas found in both treated and control animals, Marcus said. In addition, dose-dependent oral lesions noted in the Battelle report were downgraded from dysplasia and metaplasia to degeneration. Some other liver carcinomas were eventually reclassified as nonmalignant lesions. Because of what he calls systematic downgrading of the slides, Marcus has written a memo to the director of the criteria and standards division in the office of drinking water asking that EPA assemble an independent board of pathologists to review the slides again.[7]

Summary of NTP by Yiamouyiannis: 

“In 1977, Congress instructed the U.S. Public Health Service to conduct animal studies to determine whether or not fluoride causes cancer. As a result, the National Toxicology Program retained the Battelle Memorial Institute in Columbus, Ohio to perform two studies, one on mice, and another on rats.

Doctor John T. Toft, II, manager of the Pathology Section at Battelle, was placed in charge of the NTP mouse study. On October 28, 1988, after a year of analyzing these results, Doctor Toft completed the pathology narrative and final report.

The most significant finding was the occurrence of an extremely rare form of liver cancer, hepatocholangiocarcinoma in fluoride-treated male and female rats — mice, excuse me.

Among male mice, no such cancers were observed among 79 in the control group. At 11 parts per million, the lowest dose used, one was observed among 50 male mice; and 45 parts per million, one was observed among 51 male mice and at seventy-nine parts per million three were observed among 80 male mice.

Using historical controls and doing a binomial analysis of this, the odds of these results occurring by chance are less than one in two million. Normally, we consider it significant one in twenty; this is one in two million.

Making these findings even more convincing are the results with female mice. In the control group, no hepatocholangiocarcinomas were observed among eighty. At 11 parts per million, one was observed among 52. At 45 (ppm), none were observed among 50. And at 79 parts per million, three were observed among 80 female mice — female mice.

Based on these findings, and these findings alone, there was clear evidence of the carcinogenic activity of the fluoride in mice receiving 11, 45, or 79 parts per million in drinking water for two years or less.”[8]

PHS confirms risk:    The Public Health Service and NCI in 1991 report that the incidence of osteosarcoma throughout the U.S. has increased at a greater rate among young males in fluoridated areas vs. unfluoridated areas. The NCI, however, dismisses this result because of an inability to demonstrate a linear-dose relationship between the duration of fluoridation and the increased osteosarcoma incidence in fluoridated areas:

“In summary, analysis of incidence data from the SEER program has revealed some age- and sexspecific increases over time for bone and joint cancers, and for osteosarcomas, which are more prominent in fluoridated than in non-fluoridated areas. However, on further analysis these increases are unrelated to the timing of fluoridation, and thus are not linked to the fluoridation of water supplies.” (Hoover 1991)

Calabrese[9] 1993 was requested by the East Bay Municipal Utility District to conduct an independent appraisal of the 1990 NTP report.  He found the NTP’s choice of the word “equivocal” to be confusing, inappropriate and not consistent with what most people would call equivocal, for the following reasons:

  1. Its own definition of equivocal is in disagreement with the generally accepted definition of equivocal.
  2. The findings with the male rat clearly exceeded marginal increases and are biologically plausible given the capacity for fluoride to both concentrate and be biologically active in bone.
  3. The statistical analysis for trend effects is stronger than pair-wise comparisons since it uses all available data not just data from two comparison groups, yet this point is never acknowledged.
  4. The basic reality is that humans can be exposed in critical target tissues to as much fluoride as the high dose rats while consuming water at the EPA maximum contaminant level of 4 mg/liter.

 

 

[1] Bucher JR, et al. (1991). Results and conclusions of the National Toxicology Programs rodent carcinogenicity studies with sodium fluoride. International Journal of Cancer 48(5):733-7. July 9.

[2] Marcus W. (1990). Memorandum from Dr. William Marcus,to Alan B. Hais, Acting Director Criteria & Standards Division Of... of Drinking Water, US EPA. May 1, 1990.

[3] Bucher J. (1990). Testimony at Board of Scientific Counselors, National Toxicology Program; Peer Review of Draft Techn... Report of Long-Term Toxicology and Carcinogenesis Studies and Toxicity Study, Sodium Fluoride; Research Triangle Park, North Carolina, Thursday, April 26, 1990.

[4] Hamilton BF. (1989). Carcinogenesis bioassay of sodium fluoride with dosed water in B6C3F1 mice: Quality Assessment Narrative. Experimental Pathology Laboratories, Inc. p. 26-27.

[5] Bucher JR, et al. (1991). Results and conclusions of the National Toxicology Programs rodent carcinogenicity studies with sodium fluoride. International Journal of Cancer 48: 733-737.

[6] Sibbison JB. (1990). USA: More About Fluoride. The Lancet 336(8717): 737. Sept 22.

[7] Hileman B. (1990). Fluoride bioassay study under scrutiny. Chemical & Engineering News September 17

[8] Yiamouyiannis J. (1990). Testimony before Board of Scientific Counselors, National Toxicology Program; Peer Review of Draft Technical Report of Long-Term Toxicology and Carcinogenesis Studies and Toxicity Study, Sodium Fluor...; Research Triangle Park, North Carolina, Thursday, April 26, 1990.

[9] Calabrese, EJ, Lee, JR, Evaluation of the National Toxicology Program (NTP) Cancer Bioassay on Sodium Fluoride, Fluoride 26

(1) 1993  Accessed 4/25/15 http://www.fluorideresearch.org/261/files/FJ1993_v26_n1_p001-078.pdf

[10] Maurer JK, et al. 1990. Two-year carcinogenicity study of sodium fluoride in rats. Journal of the National Cancer Institute 82(13): 1118-26. July 4.

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Re: Fluoride and Cancer

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Review of Levy (2012)

Levy 2012.   As evidence of fluoride’s lack of carcinogenicity, PHS 2015 cites at 77, Levy 2012. 

The Levy 2012 study concludes that water fluoridation in the U.S. is not associated with an increased risk of osteosarcoma. Levy 2012 use a notably crude measurement for determining fluoride exposure, the National Cancer Institute’s SEER data, average fluoridation rate of the child’s STATE of residence at the time of diagnosis rather than exposure a decade earlier. 

By contrast, when the NCI conducted its analysis of the SEER data in 1990 (in which NCI found elevated rates of osteosarcoma among young males in fluoridated areas), the NCI considered the fluoridation status on the COUNTY level — a smaller unit which is less prone to classification error.  A study without significance is not proof of safety.  The Levy study thus sheds little light on fluoride’s possible relationship to osteosarcoma.  

Blakey et al (2014) [1]

“The study objective was to examine whether increased risk of primary bone cancer was associated with living in areas with higher concentrations of fluoride in drinking water.” 

This is an ecological study where cases were obtained from cancer registries and fluoride levels in drinking water from regional companies, Drinking Water Inspectorate, and Scottish Water.  The record does not show total fluoride exposure, supplements, blood, bone, urine or any other fluoride concentration measurement, nor whether the cohorts were actually drinking the water or swallowing toothpaste.  “Other sources of fluoride are not taken into consideration.”  

In contrast with Bassin’s 2006 study, cases with Blakey 2014 were divided into three age groups, 0-14, 15-29 and 30-49 years of age at diagnosis.   Bassin’s study used each year of life and contacted each water source to ensure the address while growing up actually received fluoride in the water (10% reporting error) and the subject lived in that location.  Bassin found ingestion of fluoridated water during 6-8 years of age increased cancer several years later.  By including all ages 0-14 in one group and 15-29 in another group, Blakey would have “watered down the evidence” and not account for the high risk growth spurts reported by Bassin.  Blakey assumes fluoride consumption was consistent throughout the study time-frame.

Blakey 2014 reported, “The monitoring data suggests that levels in some AF areas were much lower than 1 ppm.  Indeed, 33% of AF WSZs were below 0.7 ppm. . . and 61% of AF SAUs had such a level.  This suggest that 35% of populations residing in AF areas were being supplied with AF water dosed below the optimal level.”  

Blakely 2014 states, “Furthermore, although the overall results contradict those from Bassin’s study, the use of total accumulated fluoride dose rather than a specific time in life course prevents any direct comparisons being made.”

Osteosarcoma is a rare cancer (Blakely 2.64/million) and unless a study is carefully controlled, the data can be easily diluted, negating significance.  

Blakely’s Table 1 is produced here for the purpose of understanding the importance of age.  In this study, an increase in osteosarcoma is evident during 15-29 years of age and over 49 years of age.  Studies must include age and measured fluoride serum, urine, and bone concentrations.  Perhaps the rate of bone turnover is reduced during middle age.  Fluoride accumulates with time and seniors have higher bone fluoride concentrations perhaps triggering risk.

Age-group (years)

!                                   

Number of osteosarcoma cases

!                                     

Number of Ewing sarcoma cases

Males

Females

Total

Males

Females

Total

0-14

406

411

817

356

303

659

15-29

821

494

1315

516

284

800

30-49

266

168

434

116

75

191

0-49

1493

1073

2566

988

662

1650

  

Gelberg et al (1994)

The PHS 2015 failed to consider Gelberg KH. (1994) reporting, “When fluoride exposure

increases, the following bone responses generally occur: 1) an increase in the number of osteoblasts, 2) an increase in the rate of bone formation, 3) an increase in the serum activity of alkaline phosphatase, and 4) an inhibition of osteoblastic acid phosphatase… The increase in osteoblast proliferation and activity may increase the probability that these cells will undergo malignant transformation.”[2]

The case-control study by Gelberg, published first as a PhD dissertation (Gelberg 1994) and then later in two peer-reviewed journals (Gelberg 1995, 1997), may represent the most substantive study on fluoride/osteosarcoma previous to Bassin’s 2001 analysis.

While Gelberg has errors, such as stating cases were females when they were males, and reversing cases and controls in the “Total Fluoride” and “Toothpaste” categories in Tables 2 and 3,  primary concerns with Gelberg’s work relates to the methods used to analyze her data.

Gelberg uses data from NY Cancer Registry and state rather than county fluoridation rates. Gelberg, like Hoover 1991,[3] never analyzes her data with subjects divided into a simple two-category model: exposed versus unexposed, but rather quartiles.

However, for males the lower “quartile” group shows a borderline statistically significant increased risk OR of 2.8 (95%CI 1.0-8.1). For females the OR is even higher and statistically significant at 10.5 (95%CI 1.2-91). For both males and females in the higher “quartiles” of exposure, the ORs are no longer significant, but the risk for osteosarcoma generally stays above 1.0. If, instead of breaking the data into “quartiles”, it had been broken into just “exposed” and “unexposed”, it is quite possible the exposed group would have a significantly elevated risk for osteosarcoma compared to the unexposed group.

In looking for other possible risk factors for osteosarcoma, Gelberg (1994) found that a history of exposure to dental x-rays was significantly related to the development of osteosarcoma (OR 4.0; 95%CI 1.3-12) . Dental x-rays were, in fact, one of the few variables Gelberg examined that had an effect reaching statistical significance.  

However, increased dental x-rays would indicate possibly more frequent dental visits which indicate  more frequent topical applications of fluoride (22,300 ppm fluoride) in the dental office.  The efficacy of fluoride varnish is mixed, and risks have not been studied. 

Bassin 2006; Cohn 1992; Hoover 1991 are consistent with the National Toxicology Program’s (NTP) cancer bioassay which raised concerns that fluoride-treated male rats had a dose-dependent increase in osteosarcoma. (Bucher 1991). Although a number of studies including PHS 2015 citations have failed to detect an association between fluoride and osteosarcoma, none of these studies have measured the risk of fluoride at specific windows in time, which is the critical question with respect to fluoride and osteosarcoma.

A report by the National Academy of Sciences (NAS), titled “Drinking Water and Health”, expresses concern about a possible connection between water fluoridation and osteosarcoma in young males:

“There was an observation in the Kingston-Newburgh (Ast et al, 1956) study that was considered spurious and has never been followed up. There was a 13.5% incidence of cortical defects in bone in the fluoridated community but only 7.5% in the non-fluoridated community… Caffey (1955) noted that the age, sex, and anatomical distribution of these bone defects are `strikingly’ similar to that of osteogenic sarcoma. While progression of cortical defects to malignancies has not been observed clinically, it would be important to have direct evidence that osteogenic sarcoma rates in males under 30 have not increased with fluoridation.” (NAS 1977)

 

[1] Blakey, K, Feltbower, R et al, Is fluoride a risk factor for bone cancer?  Small area analysis of osteosarcoma and Ewing sarcoma diagnosed among 0-49-year-olds in Great Britain, 1980-2005. Int J Epidemiol. 2014 Feb; 43(1): 224-234.

[2] Gelberg KH. (1994). Case-control study of osteosarcoma. Doctoral Thesis, Yale University. p. 13.

[3] Hoover R.N., Devesa S.S., Cantor K.P., Lubin J.H., Fraumeni J.F. (1991). Time trends for bone and joint cancers and osteosarcomas in the Surveillance, Epidemiology and End R.... National Cancer Institute. In: Review of Fluoride: Benefits and Risks Report of the Ad Hoc Committee on Fluoride of the Committee to Coordinate Environmental Health and Related Programs US Public Health Service.

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