Fluoridation of bone

Fluoride stimulates bone formation by protein kinase activation mediated effects on osteoblasts. Fluorides have been used in the treatment of osteoporosis, but their anti-fracture effect is not undisputed. 

Turner, R. T., Francis, R., Brown, D., Garand, J., Hannon, K. S. Bell, N. H. (1989). The effects of fluoride on bone implant histomorphology in growing rats. Journal of Bone Mineralogy Research, 4, 477-84. 

Bone is a porous tissue composite material containing a fluid phase, a calcified bone mineral, hydroxyapatite (HA), and organic components (mainly, collagen type). The variety of cellular and noncellular components consist of approximately 69% organic and 22% inorganic material and 9% water. The principal constiments of bone tissue are calcium (Ca ), phosphate (PO ), and hydroxyl (OH ) ions and calcium carbonate. There are smaller quantities of sodium, magnesium, and fluoride. The major compound, HA, has the formula Caio(P04)g(OH)2 in its unit cell. The porosity of bone includes membrane-lined capillary blood vessels, which function to transport nutrients and ions in bone, canaliculi, and the lacunae occupied in vivo by bone cells (osteoblasts), and the micropores present in the matrix. 

Fluoride ions may be relatively abundant in groundwater at one location and practically absent in that at another site hence the rate of fluoridation of the bone (the rate of increase in the relative amount of fluorine in the bone) varies from site to site. For instance, bones buried for a short time at a site in which the groundwater is rich in fluoride may acquire much more fluorine than bones buried for a very long time at a place where there is little fluoride in the groundwater. Therefore, fluorine analysis does not provide a tool for estimating the absolute age of buried bone, but only for dating bones at the same site, comparative to each other. The relative amount of fluoride in buried bone at a particular site thus provides a clue as to the length of time the bone has been buried. 

The problem of bone mineral loss, which accompanies aging of both men and women, has recently received much attention of the scientific community because the proportion of the elderly in the population is increasing especially in Western Europe and North America (J, 2). Among the various factors which affect the integrity of the skeleton are habitual intakes of mineral nutrients such as calcium, phosphorus and fluoride. Here we report the results of our investigations on the interactions between these minerals in relation to bone and soft tissues. 

Table IV. Effect of fluoride on bone composition and strength...

Whereas much attention has been paid to the effects of dietary fluoride on the skeleton of domestic and experimental animals and man (T8), knowledge about the accumulation of fluoride in soft tissues such as heart, liver or kidney is scarce. The results in Table X indicate that the fluoride content of the kidneys of mice increased with age when the dietary Ca was low and fluoride feeding resulted in much higher levels at 653 days of age irrespective of the dietary Ca content. It is likely that such high fluoride levels had an adverse effect on kidney function. In cases of chronic fluoride intoxication, kidney function was reported to be impaired in the majority of cases (18). It should be noted that fluoride accumulated in the kidneys of mice even though the capacity of bone to store fluoride (5000 yg/g dry weight) without skeletal damage was not reached. 

Fluoride, Fluoride Is contained In water and In the diet (22,23) Also, fluoride stabilizes the bone crystal (24) and has been shown to decrease bone resorption (25), For these reasons, fluoride has been recommended for the treatment for osteoporosis (26-28), The Importance of the role of fluoride on maintaining the normal bone structure Is also Indicated by a survey which showed that the Incidence of osteoporosis was lower In naturally high fluoride areas than In areas where the fluoride content of the drinking water was low (29) This observation would Indicate that the Intake of certain amounts of fluoride throughout life may be necessary for the maintenance of the normal skeleton, and that fluoride may protect the skeleton from the development of bone loss which leads to osteoporosis with advancing age, particularly In females. 

Repeated exposure to excessive concentrations of fluoride over a period of years results in increased radiographic density of bone and eventually may cause skeletal fluorosis. Crip-... 

Repeated exposure to excessive concentrations of hydrogen fluoride over a period of years may result in an increased radiographic density of bone and eventually may cause crippling fluorosis (osteosclerosis due to deposition of fluoride in bone)/ The early signs of increased bone density from fluoride deposition are most apparent in the lumbar spine and pelvis and can be detected by X ray. 

HF solutions in contact with skin result in marked tissue destruction undissociated FIF readily penetrates skin and deep tissue, where the corrosive fluoride ion can cause necrosis of soft tissues and decalcification of bone the destruction produced is excruciatingly painful.Fluoride ion also attacks enzymes (e.g., of glycolysis) and cell membranes. The process of tissue destruction and neutralization of the hydrofluoric acid is prolonged for days, unlike other acids, which are rapidly neutral-ized. ° Because of the insidious manner of penetration, a relatively mild or minor exposure can cause a serious burn. When skin contact is with solutions of less than 20%, the burn manifests itself by pain and erythema with a... 

Fluoride is the salt, such as sodium fluoride, of the element fluorine. It is readily absorbed by the intestine and is incorporated into bone or tooth enamel. When incorporated into teeth, fluoride strengthens the outer layers of enamel, thus reducing dental caries. It is generally accepted that addition of fluoride to the drinking water (approximately 1 ppm) is beneficial for the reduction in childhood dental caries. 

F]-Fluoride-PET Imaging of bone metastases [ F]FET-PET Imaging with amino acids [ F]Fluorodopa-PET Imaging with amino precursors Acknowledgments References Note from the Editors... 

Schirrmeister et al. prospectively evaluated the clinical value of planar bone scans, SPECT and [ F]-labeled sodium fluoride in 53 patients with newly diagnosed lung cancer [193], Twelve of the 53 patients turned out to have bone metas-tases. [ F]-fluoride-PET detected all patients with bone metastases, whereas bone scan and SPECT produced false-negative results (6 vs. 1). An area under the curve analysis (ROC) proved p F]-fluoride-PET to be the most accurate whole-body imaging modality for screening of bone metastases in this study. 

In another study by the same group, [ F]-fluoride-PET/CT was compared with [ F]-fluoride-PET, bone scintigraphy and SPECT in 44 patients with high-risk prostate cancer [195]. For detection of skeletal metastatic spread [ F]-fluoride-PET/CT revealed to be significantly more sensitive and specific than bone scintigraphy (p < 0.05) and SPECT (p < 0.05), and significantly more specific than [i F]-fluoride-PET (p < 0.001). 

G.M. Blake, S.J. Park-Holohan, G.J. Cook, I. Fogelman, Quantitative studies of bone with the use of F-fluoride and 99mTc-methylene diphosphonate, Semin. Nucl. Med. 31(1) (2001) 28-49. 

E. Even-Sapir, U. Metser, E. Mishani, G. Lievshitz, H. Lerman, I. Leibovitch, The detection of bone metastases in patients with high-risk prostate cancer 99mTc-MDP planar bone scintigraphy, single- and multi-field-of-view SPECT, F-fluoride PET, and F-fluoride PET/CT, J. Nucl. Med. 47(2) (2006) 287-297. 

W. Langsteger, M. Heinisch, I. Fogelman, The role of fluorodeoxyglucose, F-dihydroxyphenylalanine, F-choline, and F-fluoride in bone imaging with emphasis on prostate and breast, Semin. Nucl. Med. 36(1) (2006) 73-92. 

Two processes have been proposed to explain the mitogenic effect of fluoride on bone cells involving either fluoride ions directly or the AIF complex (Fig. 11). Fluoride ions have been shown to directly inhibit an enzyme (tyrosine phophory-lase phosphatase) resulting in an enhancement of the tyrosine phosphorylation part of the mitogen-activated protein kinase system (MARK) [177], The other activation pathway involves a complex of aluminium and fluoride which activates the G-protein and stimulates tyrosine phophorylation resulting in an enhanced mitogenic effect [176]. 

K.H. Lau, T.K. Freeman, D.J. Baylink, A proposed mechanism of the mitogenic action of fluoride on bone cells. Inhibition of the activity of an osteoblastic acid phosphatase, Metabolism 38 (1989) 858-868. 

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