Abstract
Receptor activator of nuclear factor kappa-B ligand (RANKL) acting on osteoblasts is an essential cytokine for osteoclast formation. Recent studies have shown that fluoride (F) can stimulate RANKL expression of osteoblasts. However, the effect of F under various levels of RANKL on osteoclast formation is not clear. In this study, stem cell technology was used to observe the effect of F on osteoclast formation at different levels of treatment with RANKL. Our results show that F significantly inhibits the formation of osteoclasts treated with 50 ng/mL RANKL. The number of osteoclasts in the 0.5 mg/L F group fell to about 60% of the control group with no further significant change at the higher fluoride concentrations used (2 and 8 mg/L). On the other hand, F had no effect on the formation of osteoclasts treated with 100 ng/mL RANKL. In fact, the number of osteoclasts formed at 100 ng/mL RANKL was significantly higher than at the 50 ng/mL RANKL level. However, F significantly decreased the activity of osteoclast bone resorption even at a low level of 0.5 mg/L F, and the higher the F concentration was, the lower the activity of bone resorption became. Therefore we conclude that the main effect of F on osteoclasts was the inhibition of their capacity for bone resorption, thus resulting in osteosclerosis as the major clinical manifestation in patients with skeletal fluorosis.
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The pathogenesis of endemic fluorosis: Research progress in the last 5 years.
Fluorine is one of the trace elements necessary for health. It has many physiological functions, and participates in normal metabolism. However, fluorine has paradoxical effects on the body. Many studies have shown that tissues and organs of humans and animals appear to suffer different degrees of damage after long-term direct
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Histopathological assessment of endemic skeletal fluorosis
Nine patients with skeletal fluorosis were subjected to iliac crest biopsy because they presented with stiffness and bone pains. The histopathological findings are correlated with the clinical course, X-ray and laboratory data. All but one of the patients showed an increase in bone surfaces lined by osteoid and in these
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Experimental fluorosis in rats: NaF induced changes of bone and bone marrow
The results of our experiments suggest that increased doses of NaF cause more extensive osteosclerosis due to the decrease in number and/or activity of osteoclasts. Therefore oateosclerosis is caused primarily, not by increased bone formation but, by the inhibition of bone resorption. This view is supported by the fact that
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Is the severity of osteosclerosis of fluorosis proportional to the dose of fluoride intake?
Histomorphometric study was made on a series of sections of undecalcified epiphyseal femoral specimens from rats with experimental fluorosis. The results revealed osteosclerosis in Group A (5 ppm) being more severe than that in Group B (25 ppm). With the increase of fluoride dose, the parameters fell down instead of
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Aberrant methylation-induced dysfunction of p16 is associated with osteoblast activation caused by fluoride.
Chronic exposure to fluoride continues to be a public health problem worldwide, affecting thousands of people. Fluoride can cause abnormal proliferation and activation of osteoblast and osteoclast, leading to skeletal fluorosis that can cause pain and harm to joints and bones and even lead to permanent disability. Nevertheless, there is
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Fluoride & Osteoarthritis
While the osteoarthritic effects that occurred from fluoride exposure were once considered to be limited to those with skeletal fluorosis, recent research shows that fluoride can cause osteoarthritis in the absence of traditionally defined fluorosis. Conventional methods used for detecting skeletal fluorosis, therefore, will fail to detect the full range of people suffering from fluoride-induced osteoarthritis.
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"Pre-Skeletal" Fluorosis
As demonstrated by the studies below, skeletal fluorosis may produce adverse symptoms, including arthritic pains, clinical osteoarthritis, gastrointestinal disturbances, and bone fragility, before the classic bone change of fluorosis (i.e., osteosclerosis in the spine and pelvis) is detectable by x-ray. Relying on x-rays, therefore, to diagnosis skeletal fluorosis will invariably fail to protect those individuals who are suffering from the pre-skeletal phase of the disease. Moreover, some individuals with clinical skeletal fluorosis will not develop an increase in bone density, let alone osteosclerosis, of the spine. Thus, relying on unusual increases in spinal bone density will under-detect the rate of skeletal fluoride poisoning in a population.
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Skeletal Fluorosis: The Misdiagnosis Problem
It is a virtual certainty that there are individuals in the general population unknowingly suffering from some form of skeletal fluorosis as a result of a doctor's failure to consider fluoride as a cause of their symptoms. Proof that this is the case can be found in the following case reports of skeletal fluorosis written by doctors in the U.S. and other western countries. As can be seen, a consistent feature of these reports is that fluorosis patients--even those with crippling skeletal fluorosis--are misdiagnosed for years by multiple teams of doctors who routinely fail to consider fluoride as a possible cause of their disease.
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Skeletal Fluorosis in the U.S.
Although there has been a notable absence of systematic studies on skeletal fluorosis in the U.S., the available evidence indicates that the consumption of artificially fluoridated water is likely to cause skeletal fluorosis and other forms of bone disease in people with kidney disease and other vulnerable populations.
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Fluoride Magnifies Impact of Repetitive Stress on Joints
Research has repeatedly found that fluoride's effect on the skeleton is most pronounced in the bones and joints that undergo the greatest strain. Indeed, both the symptoms of fluorosis (i.e., joint pain and stiffness) as well as the radiological findings (e.g., exostoses, interosseuous membrane calcification) have been found to occur earliest, and most severely, in the joints
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