NOTE: The following article, while providing an insightful examination of skeletal fluorosis, contains a significant piece of outdated information. According to the article: "Most experts in skeletal fluorosis agree that ingestion of 20 mg of fluoride a day for 20 years or more can cause crippling skeletal fluorosis. " This view has changed however since the publication of this article.

In 1993, the National Research Council stated that crippling fluorosis may be caused by as little as 10 mg/day of fluoride. To quote:

"Crippling skeletal fluorosis might occur in people who have ingested 10-20 mg of fluoride per day for 10-20 years."

Excerpt from:

CHEMICAL & ENGINEERING NEWS

August 1, 1988

Fluoridation of Water
Questions about health risks and benefits remain after more than 40 years

Bette Hileman,
C&EN Washington

Skeletal Fluorosis

One solidly established concept in environmental health is that the effects of toxic agents fall on a continuum of biological change, ranging from undetectable effects at the lowest levels of exposure to severe health damage at very high doses. As exposure to an agent increases, the first detectable effect may be a subtle biochemical change, such as a decrease in the activity of an enzyme. At somewhat higher doses, measurable changes in some physiological functions may occur, but these often are not linked to clear symptoms or adverse effects, and may not be harmful. But as dosage increases, adverse effects begin to appear-at first mild ones, then moderate ones, and finally severe ones.

Most environmental health experts believe that the subtlest detectable effects-those with no outward symptoms, which are not clearly harmful-should be considered "precursors" of more serious effects. By this logic, people who show such subtle changes should be considered at risk for more serious effects if exposure continues.

Skeletal fluorosis, a complicated illness caused by the accumulation of too much fluoride in the bones, has a number of stages. The first two stages are preclinical-that is, the patient feels no symptoms but changes have taken place in the body. In the first preclinical stage, biochemical abnormalities occur in the blood and in bone composition; in the second, histological changes can be observed in the bone in biopsies. Some experts call these changes harmful because they are precursors of more serious conditions. Others say they are harmless.

In the early clinical stage of skeletal fluorosis, symptoms include pains in the bones and joints; sensations of burning, pricking, and tingling in the limbs; muscle weakness; chronic fatigue; and gastrointestinal disorders and reduced appetite. During this phase, changes in the pelvis and spinal column can be detected on x-rays. The bone has both a more prominent and more blurred structure.

In the second clinical stage, pains in the bones become constant and some of the ligaments begin to calcify. Osteoporosis may occur in the long bones, and early symptoms of osteosclerosis (a condition in which the bones become more dense and have abnormal crystalline structure) are present. Bony spurs may also appear on the limb bones, especially around the knee, the elbow, and on the surface of tibia and ulna.

In advanced skeletal fluorosis, called crippling skeletal fluorosis, the extremities become weak and moving the joints is difficult. The vertebrae partially fuse together, crippling the patient.

Most experts in skeletal fluorosis agree that ingestion of 20 mg of fluoride a day for 20 years or more can cause crippling skeletal fluorosis (SEE NOTE ABOVE). Doses as low as 2 to 5 mg per day can cause the preclinical and earlier clinical stages. The situation is complicated because the risk of skeletal fluorosis depends on more than the level of fluoride in the water. It also depends on nutritional status, intake of vitamin D and protein, absolute amount of calcium and ratio of calcium to magnesium in drinking water, and other factors.

In parts of India, China, Africa, Japan, and the Middle Fast, large numbers of people have skeletal fluorosis from drinking naturally fluoridated water. In India about a million people have this disease. Most of the victims live in areas where the water fluoride level is 2 ppm or above, but some cases are found in communities with natural fluoride levels below 1 ppm.

In the U.S., more than a dozen cases of skeletal fluorosis have been reported. Some have occurred at high fluoride levels, others at levels lower than 4 ppm when aggravating conditions were present, such as diabetes or impaired kidney function.

In setting the recommended maximum contaminant level for fluoride in drinking water in 1986, EPA considered only crippling skeletal fluorosis as a health effect and established little or no margin of safety, even for this disease. (A margin of safety is a difference between the maximum contaminant level and the level at which health effects first occur in the most susceptible individuals.) According to a Department of Agriculture survey, about 3% of the U.S. population drinks 4 L or more or water per day. Therefore, about 3 % of the people who live in areas where the water contains the natural fluoride level of 4 ppm allowed by EPA -- such as certain communities in Texas or South Carolina -- are ingesting at least 16 mg of fluoride a day, not including the fluoride they derive from other sources, such as toothpaste, food, or air.

Also, because a more or less constant percent of intake is accumulated in bone, persons who consume 8 mg a day for 50 years accumulate about the same amount of fluoride in their bones as those who consume 20 mg a day for 20 years. Therefore, for people who drink 2 L or more per day of water with 4 ppm fluoride throughout their lives, there appears to be no margin of safety even for crippling fluorosis. In its regulations for most other drinking water contaminants, EPA has included safety factors of 10 to 100 and has calculated intakes in terms of a lifetime—that is, 70 years instead of 20.

Joseph A. Cotruvo, director of the criteria and standards division of EPA’s Office of Drinking Water, says the fact that so few people in the U.S. have actually developed crippling skeletal fluorosis indicates that fluoride levels found in U.S. water are safe and that there is therefore an observed margin of safety. But critics of EPA’s standard speculate that there probably have been many more cases of fluorosis-even crippling fluorosis-than the few reported in the literature because most doctors in the U.S. have not studied the disease and do not know how to diagnose it.

Those who ingest much less than 20 mg of fluoride per day may still be at risk of developing less severe stages of skeletal fluorosis, such as preclinical forms or the subcrippling clinical stages. In its final report, the Surgeon General’s panel said that radiologic changes have been found in bone when fluoride exposure has been about 5 mg per day. Nearly all of those drinking water containing 4 ppm of fluoride and about 3% of the more than 124 million people whose water contains only 1 ppm would have intakes as high as this. It is not known, however, what fraction of those with low-level radiologic changes would suffer joint pains or other clinically obvious adverse health effects. In his landmark study of skeletal fluorosis in cryolite workers in the 1930s, the Danish scientist Kaj Roholm found that some of those with stage I of clinical skeletal fluorosis suffered joint pains and stiffness.

Although skeletal fluorosis has been studied intensely in other countries for more than 40 years, virtually no research has been done in the U.S. to determine how many people are afflicted with the earlier stages of the disease, particularly the preclinical stages. Because some of the clinical symptoms mimic arthritis, the first two clinical phases of skeletal fluorosis could be easily misdiagnosed. Skeletal fluorosis is not even discussed in most medical texts under the effects of fluoride; indeed, a number of texts say the condition is almost nonexistent in the U.S. Even if a doctor is aware of the disease, the early stages are difficult to diagnose.

The possibility that fluoride might cause skeletal abnormalities in children’s bones is of particular concern. In its April 1983 draft report, the Surgeon General’s committee wrote that moderate and severe dental fluorosis in children may be accompanied by skeletal changes. Although this statement was omitted from the final report in September 1983, the committee did urge more research into the skeletal effects of fluoride, particularly in children. It wrote: "The effects of various levels of fluoride intake on rapidly developing bone in young children are not well understood. Also, the modifying effects of total intake, length of exposure, other nutritional factors, and debilitating illness are not well understood." Since the committee’s report was written, PHS and EPA have undertaken no research in this area.

PHS has conducted several studies that it claims show that fluoride levels found in U.S. water supplies have had no clearly adverse effects on bones. But the majority of these studies either included a study population too small to detect rare effects or excluded people who would be most likely to suffer from skeletal fluorosis, such as those with kidney disease.

EPA’s approach to subtle, preclinical effects of fluoride on the skeleton differs from its usual approach to other environmental agents. For instance, when EPA assessed the health hazards of lead, it made an extraordinary effort to connect the observable effects of low-level exposure (inhibition of certain blood enzymes) with the known adverse effects of slightly higher exposure (decreased synthesis of hemoglobin, anemia, and possible neurotoxic effects). When it set its standard for lead in air, EPA argued that to prevent more serious effects, it needed to limit the more subtle biochemical changes that lead was provoking in millions of children.

By contrast, EPA’s assessment of fluoride in water took an almost opposite tack. By defining the most severe known hazard, crippling skeletal fluorosis, as the only effect it was concerned with preventing, EPA dismissed all degrees of fluoride-induced changes in bones less drastic than crippling fluorosis as not being health concerns...

Kidney disease

Two areas are of concern in regard to fluoride and kidneys. First, a fairly substantial body of research indicates that people with kidney dysfunction are at increased risk of developing some degree of skeletal fluorosis. Second, a small and inconclusive amount of research suggests that fluoride may actually cause or aggravate kidney disease.

D. Raja Reddy of the Gandhi Medical College in India claims, for example, that "patients suffering from chronic kidney diseases and those with transplanted kidneys do excrete fluoride, though in small quantities, but they are more vulnerable to osteofluorosis and even neurological complications than others." In its final report, the Surgeon General’s 1983 committee notes, "As renal function declines, due either to diseases or with aging, plasma and bone fluoride content both increase."

The National Kidney Foundation in its "Position Paper on Fluoridation-1980" also expresses concern about fluoride retention in kidney patients. It cautions doctors "to monitor the fluoride intake of patients with chronic renal impairment, but stops short of recommending the use of fluoride-free drinking water for all patients with kidney disease. It does recommend, however, that dialysis patients use fluoride-free water for their treatments.

Studies show that children with moderately impaired renal function (such as those who have diabetes insipidus), are at some risk of skeletal changes from consumption of fluoridated water, even if the fluoride level is no higher than 1 ppm. A number of researchers have found high concentrations of fluoride in the bones of patients who suffer from kidney disease and have found symptoms of skeletal fluorosis in some of these patients. However, there has been no systematic survey of people with impaired kidney function to determine how many actually suffer a degree of skeletal fluorosis that is clearly detrimental to their health.

Several animal studies suggest that fluoride may have direct adverse effects on the kidneys. For instance, cytological and enzyme changes have been found in the kidneys of squirrel monkeys drinking water with 5 ppm fluoride. It is not known how the changes affect kidney function in monkeys, nor is it known whether humans would suffer similar changes from relatively low levels of fluoride in drinking water. Impaired renal function, however, has been reported to be more common in areas of endemic skeletal fluorosis.

See also:

Fluoride & Arthritis - Fluoride Action Network September 2003

Skeletal Fluorosis: Recent Reports from India - Compilation of articles

The Effect of Fluorosis on Joints - FLUORIDE, January 1976