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APPENDICES for The Case Against Fluoride

The Case Against Fluoride
How Hazardous Waste Ended Up in Our Drinking Water
and the Bad Science and Powerful Politics That Keep It There

By Paul Connett, James Beck and H.S. Micklem
Published by Chelsea Green, 2010

See also: ENDNOTES

Fluoride and the Brain

Twenty-three human studies that report an association of lowered IQ with fluoride exposure.

Y. Chen, F. Han, Z. Zhou, et al., “Research on the Intellectual Development of Children in High Fluoride Areas,” Fluoride 41, no. 2 (2008): 120–24, (originally published in 1991 in Chinese Journal of Control of Endemic Diseases), http://www.fluorideresearch.org/412/files/FJ2008_v41_n2_p120-124.pdf

X. Guo, R. Wang, C. Cheng, et al., “A Preliminary Investigation of the IQs of 7–13 Year Old Children from an Area with Coal Burning-Related Fluoride Poisoning,” Fluoride 41, no. 2 (2008): 125–28 (originally published in 1991 in Chinese Journal of Endemiology), http://www.fluorideresearch.org/412/files/FJ2008_v41_n2_p125-128.pdf

F. Hong, Y. Cao, D. Yang, and H. Wang, “Research on the Effects of Fluoride on Child Intellectual Development Under Different Environmental Conditions,” Fluoride 41, no. 2 (2008): 156–60 (originally published in 2001 in Chinese Primary Health Care), http://www.fluorideresearch.org/412/files/FJ2008_v41_n2_p156-160.pdf

X. S. Li, J. L. Zhi, and R.O. Gao, “Effect of Fluoride Exposure on Intelligence in Children,” Fluoride 28, no. 4 (1995): 189–92, http://fluoridealert.org/scher/li-1995.pdf

Y. Li, X. Jing, D. Chen, L. Lin, and Z. Wang, “Effects of Endemic Fluoride Poisoning on the Intellectual Development of Children in Baotou,” Fluoride 41, no. 2 (2008): 161–64 (origi­nally published in 2003 in Chinese Journal of Public Health Management), http://www.fluorideresearch.org/412/files/FJ2008_v41_n2_p161-164.pdf

F. F. Lin, Aihaiti, H. X. Zhao, et al., “The Relationship of a Low-Iodine and High-Fluoride Environment to Subclinical Cretinism in Xinjiang,” Xinjiang Institute for Endemic Disease Control and Research; Office of Leading Group for Endemic Disease Control of Hetian Prefectural Committee of the Communist Party of China; and County Health and Epidemic Prevention Station, Yutian, Xinjiang, Iodine Deficiency Disorder Newsletter 7, (1991): 3, http://fluoridealert.org/scher/lin-1991.pdf -also see http://www.fluoridealert.org/IDD.htm

S. Liu, Y. Lu, Z. Sun, et al., “Report on the Intellectual Ability of Children Living in High-Fluoride Water Areas,” Fluoride 41, no. 2 (2008): 144–47 (originally published in 2000 in Chinese Journal of Control of Endemic Diseases), http://www.fluorideresearch.org/412/files/FJ2008_v41_n2_p144-147.pdf

Y. Lu, Z. R. Sun, L. N. Wu, et al., “Effect of High-Fluoride Water on Intelligence in Children,” Fluoride 33, no. 2 (2000): 74–78, http://www.fluorideresearch.org/332/files/FJ2000_v33_n2_p74-78.pdf

L. Qin, S. Huo, R. Chen, et al., “Using the Raven’s Standard Progressive Matrices to Determine the Effects of the Level of Fluoride in Drinking Water on the Intellectual Ability of School-Age Children,” Fluoride 41, no. 2 (2008): 115–19 (originally published in 1990 in Chinese Journal of the Control of Endemic Disease), http://www.fluorideresearch.org/412/files/FJ2008_v41_n2_p115-119.pdf

D. Ren, K. Li, and D. Liu, “A Study of the Intellectual Ability of 8–14 Year-Old Children in High Fluoride, Low Iodine Areas,” Fluoride 41, no. 4 (2008): 319–20 (originally published in 1989 in Chinese Journal of Control of Endemic Diseases), http://www.fluorideresearch.org/414/files/FJ2008_v41_n4_p319-320.pdf

D. Rocha-Amador, M. E. Navarro, L. Carrizales, et al., “Decreased Intelligence in Children and Exposure to Fluoride and Arsenic in Drinking Water,” Cadernos de Saúde Pública 23, suppl. 4 (2007): S579–87.

B. Seraj, M. Shahrabi, M. Falahzade, et al., “Effect of High Fluoride Concentration in Drinking Water on Children’s Intelligence,” Journal of Dental Medicine 19, no. 2 (2007): 80–86. Note: English translation forwarded by lead author (B. Seraj, department of pediatric dentistry, faculty of dentistry, Tehran University of Medical Sciences), http://fluoridealert.org/scher/seraj-2007.trans.pdf

M. H. Trivedi, R. J. Verma, N. J. Chinoy, et al., “Effect of High Fluoride Water on Intelligence of School Children in India,” Fluoride 40, no. 3 (2007): 178–83, http://www.fluorideresearch.org/403/files/FJ2007_v40_n3_p178-183.pdf

G. Wang, D. Yang, F. Jia, and H. Wang, “A Study of the IQ Levels of Four- to Seven-Year-Old Children in High Fluoride Areas,” Fluoride 41, no. 4 (2008): 340–43 (originally published in 1996 in Endemic Diseases Bulletin [China]), http://www.fluorideresearch.org/414/files/FJ2008_v41_n4_p340-343.pdf

S. Wang, H. Zhang, W. Fan, et al., “The Effects of Endemic Fluoride Poisoning Caused by Coal Burning on the Physical Development and Intelligence of Children,” Fluoride 41, no. 4 (2008): 344–48 (originally published in 2005 in Journal of Applied Clinical Pediatrics [China]), http://www.fluorideresearch.org/414/files/FJ2008_v41_n4_p344-348.pdf

S. X. Wang, Z. H. Wang, X. T. Cheng, et al., “Arsenic and Fluoride Exposure in Drinking Water: Children’s IQ and Growth in Shanyin County, Shanxi Province, China,” Environmental Health Perspectives 115, no. 4 (2007): 643–47, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1852689/

Q. Xiang, Y. Liang, L. Chen, et al., “Effect of Fluoride in Drinking Water on Children’s Intelligence,” Fluoride 36, no. 2 (2003): 84–94, http://www.fluorideresearch.org/362/files/FJ2003_v36_n2_p84-94.pdf - Also see Q. Xiang, Y. Liang, M. Zhou, and H. Zang, “Blood Lead of Children in Wamiao -Xinhuai Intelligence Study” (letter), Fluoride 36, no. 3 (2003): 198–99, http://www.fluorideresearch.org/363/files/FJ2003_v36_n3_p198-199.pdf

L. B. Zhao, G. H. Liang, D. N. Zhang, and X. R. Wu, “Effect of High-Fluoride Water Supply on Children’s Intelligence,” Fluoride 29, no. 4 (1996): 190–92, http://fluoridealert.org/scher/zhao-1996.pdf

The following five Chinese I.Q. studies have not yet been translated:

J. A. An, S. Z. Mei, A. P. Liu, et al., “Effect of High Level of Fluoride on Children’s Intelligence” (article in Chinese), Zhong Guo Di Fang Bing Fang Zhi Za Zhi 7, no. 2 (1992): 93–94.

Z. X. Fan, H. X. Dai, A. M. Bai, et al., “Effect of High Fluoride Exposure on Children’s Intelligence” (article in Chinese), Huan Jing Yu Jian Kang Za Zhi 24, no. 10 (2007): 802–3.

Y. L. Xu, C. S. Lu, and X. N. Zhang, “Effect of Fluoride on Children’s Intelligence” (article in Chinese), Di Fang Bing Tong Bao 9 (1994): 83–84.

L. M. Yao, Y. Deng, S. Y. Yang, et al., “Comparison of Children’s Health and Intelligence Between the Fluorosis Area with Altering Water Source and Those without Altering Water Source” (article in Chinese), Yu Fang Yi Xue Wen Xian Xin Xi 3, no. 1 (1997): 42–43.

J. W. Zhang, H. Yao, and Y. Chen, “Effect of High Level of Fluoride and Arsenium on Children’s Intelligence” (article in Chinese), Zhong Guo Gong Gong Wei Sheng Xue Bao 17, no. 2 (1998): 119.
Animal and biochemical studies in chronological order
(This is a list of some of the studies that have been published.)

S. Ochoa, “‘Coupling’ of Phosphorylation with Oxidation of Pyruvic Acid in Brain,” The Journal of Biological Chemistry 138 (1941): 751–73, http://www.jbc.org/content/138/2/751.full.pdf+html

E. Racker and H. Kabat, “The Metabolism of the Central Nervous System in Experimental Poliomyelitis,” The Journal of Experimental Medicine 76, no. 6 (1942): 579–85, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2135281/

D. Nachmansohn and A. L. Machado, “The Formation of Acetylcholine. A New Enzyme: ‘Choline Acetylase,’” Journal of Neurophysiology 6 (1943): 397–403.

G. Cimasoni, “Inhibition of Cholinesterases by Fluoride In Vitro,” The Biochemical Journal 99, no. 1 (1966): 133–37, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1264967/

J. P. Perkins and M. M. Moore, “Adenyl Cyclase of Rat Cerebral Cortex. Activation of Sodium Fluoride and Detergents,” The Journal of Biological Chemistry 246, no. 1 (1971): 62–68, http://www.jbc.org/content/246/1/62.long

R. A. Johnson and E. W. Sutherland, “Detergent-Dispersed Adenylate Cyclase from Rat Brain. Effects of Fluoride, Cations, and Chelators,” The Journal of Biological Chemistry 248, no. 14 (1973): 5114–21, http://www.jbc.org/content/248/14/5114.long

S. Katz and A. Tenenhouse, “The Relation of Adenyl Cyclase to the Activity of Other ATP Utilizing Enzymes and Phosphodiesterase in Preparations of Rat Brain; Mechanism of Stimulation of Cyclic AMP Accumulation by NaF,” British Journal of Pharmacology 48, no. 3 (1973): 505–15, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1776132/pdf/brjpharm00545-0143.pdf

K. Czechowicz, A. Osada, and B. Slesak, “Histochemical Studies on the Effect of Sodium Fluoride on Metabolism in Purkinje’s Cells,” Folia Histochemica et Cytochemica (Krakow) 12, no. 1 (1974): 37–44.

L. I. Popov, R. I. Filatova, and A. S. Shershever, “Aspects of Nervous System Affections in Occupational Fluorosis” (article in Russian), Gigiena Truda I Professional’nye Zabolevaniia, no. 5 (1974): 25–27.

S. L. Manocha, H. Warner, and Z. L. Olkowski, “Cytochemical Response of Kidney, Liver and Nervous System to Fluoride Ions in Drinking Water,” Histochemical Journal 7, no. 4 (1975): 343–55.

C. O. Brostrom, M. A. Brostrom, and D. J. Wolff, “Calcium-Dependent Adenylate Cyclase from Rat Cerebral Cortex. Reversible Activation by Sodium Fluoride,” The Journal of Biological Chemistry 252, no. 16 (1977): 5677–85, http://www.jbc.org/content/252/16/5677.long

V. I. Tokar’ and O. N. Savchenko, “Effect of Inorganic Fluorine Compounds on the Functional State of the Pituitary-Testis System” (article in Russian), Problemy E’ndokrinologii (Mosk) 23, no. 4 (1977): 104–7.

M. Hebdon, H. Le Vine III, N. Sahyoun, et al., “Properties of the Interaction of Fluoride- and Guanylyl-5’-Imidodiphosphate-Regulatory Proteins with Adenylate Cyclase,” Proceedings of the National Academy of Sciences of the United States of America 75, no. 8 (1978): 3693–97, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC392852/pdf/pnas00020-0163.pdf

C. F. Hongslo, J. K. Hongslo, and R. I. Holland, “Fluoride Sensitivity of Cells from Different Organs,” Acta Pharmacologica et Toxicologica 46, no. 1 (1980): 73–77.

M. M. Rasenick and M. W. Bitensky, “Partial Purification and Characterization of a Macromolecule which Enhances Fluoride Activation of Adenylate Cyclase,” Proceedings of the National Academy of Sciences of the United States of America 77, no. 8 (1980): 4628–32, http://fluoridealert.org/re/rasenick-1980.pdf

T. Nanba, M. Ando, Y. Nagata, et al., “Distribution and Different Activation of Adenylate Cyclase by NaF and of Guanylate Cyclase by NaN3 in Neuronal and Glial Cells Separated from Rat Cerebral Cortex,” Brain Research 218, no. 1–2 (1981): 267–77.

T. Tomomatsu, “Hygienic Study on Fluoride (4). Physiological Effects of Fluoride on Rat,” J Tokyo Med Coll. 39, no. 3 (1981): 441–60.

G. Janiszewska, L. Lachowicz, and R. Wojtkowiak, “Effect of Certain Agents on Subcellular cAMP Level in Different Areas of Rat Brain,” Acta Physiologica Polonica 35, no. 3 (1984): 199–206.

M. G. Soni, M. S. Kachole, and S. S. Pawar, “Alterations in Drug Metabolising Enzymes and Lipid Peroxidation in Different Rat Tissues by Fluoride,” Toxicology Letters 21, no. 2 (1984): 167–72.

F. Geeraerts, G. Gijs, E. Finne, and R. Crokaert, “Kinetics of Fluoride Penetration in Liver and Brain,” Fluoride 19, no. 3 (1986): 108–12.

Z. Z. Guan, “Morphology of the Brain of the Offspring of Rats with Chronic Fluorosis” (article in Chinese), Zhonghua Bing Li Xue Za Zhi 15, no. 4 (1986): 297–99.

A. R. Kay, R. Miles, and R. K. Wong, “Intracellular Fluoride Alters the Kinetic Properties of Calcium Currents Facilitating the Investigation of Synaptic Events in Hippocampal Neurons,” The Journal of Neuroscience 6, no. 10 (1986): 2915–20, http://www.jneurosci.org/cgi/reprint/6/10/2915

I. Litosch, “Guanine Nucleotide and NaF Stimulation of Phospholipase C Activity in Rat Cerebral-Cortical Membranes. Studies on Substrate Specificity,” The Biochemical Journal 244, no. 1 (1987): 35–40, http://www.biochemj.org/bj/244/0035/2440035.pdf

P. P. Godfrey and S. P. Watson, “Fluoride Inhibits Agonist-Induced Formation of Inositol Phosphates in Rat Cortex,” Biochemical and Biophysical Research Communications 155, no. 2 (1988): 664–69.

R. S. Jope, “Modulation of Phosphoinositide Hydrolysis by NaF and Aluminum in Rat Cortical Slices,” Journal of Neurochemistry 51, no. 6 (1988): 1731–36.

R. S. Jope and K. M. Lally, “Synaptosomal Calcium Influx is Activated by Sodium Fluoride,” Biochemical and Biophysical Research Communications 151, no. 2 (1988): 774–80.

W. X. Liu, “Experimental Study of Behavior and Cerebral Morphology of Rat Pups Generated by Fluorotic Female Rat” (article in Chinese), Zhonghua Bing Li Xue Za Zhi 18, no. 4 (1989): 290–92.

H. Machida, “The Rabbit Thermo-Regulatory System. Effects of High Dose of Sodium Fluoride” (article in Japanese), Shikwa Gakuho 89, no. 3 (1989): 607–26.

E. Claro, M. A. Wallace, and J. N. Fain, “Dual Effect of Fluoride on Phosphoinositide Metabolism in Rat Brain Cortex. Stimulation of Phospholipase C and Inhibition of Polyphosphoinositide Synthesis,” The Biochemical Journal 268, no. 3 (1990): 733–37, http://www.biochemj.org/bj/268/0733/2680733.pdf

I. M. Gardiner and J. de Belleroche, “Modulation of Gamma-Aminobutyric Acid Release in Cerebral Cortex by Fluoride, Phorbol Ester, and Phosphodiesterase Inhibitors: Differential Sensitivity of Acetylcholine Release to Fluoride and K+ Channel Blockers,” Journal of Neurochemistry 54, no. 4 (1990): 1130–35.

P. P. Li, D. Sibony, and J. J. Warsh, “Guanosine 5’-O-Thiotriphosphate and Sodium Fluoride Activate Polyphosphoinositide Hydrolysis in Rat Cortical Membranes by Distinct Mechanisms,” Journal of Neurochemistry 54, no. 4 (1990): 1426–32.

G. Tiger, P. E. Björklund, G. Brannstrom, and C. J. Fowler, “Multiple Actions of Fluoride Ions Upon the Phosphoinositide Cycle in the Rat Brain,” Brain Research 537, no. 1–2 (1990): 93–101.

G. Tiger, P. E. Björklund, R. F. Cowburn, et al., “Effect of Monovalent Ions upon G Proteins Coupling Muscarinic Receptors to Phosphoinositide Hydrolysis in the Rat Cerebral Cortex,” European Journal of Pharmacology 188, no. 1 (1990): 51–62.

S. J. Publicover, “Brief Exposure to the G-Protein Activator NaF/AlCl3 Induces Prolonged Enhancement of Synaptic Transmission in Area CAl of Rat Hippocampal Slices,” Experimental Brain Research 84, no. 3 (1991): 680–84.

S. D. Yuan, K. Q. Song, Q. W. Xie, and F. Y. Lu, “An Experimental Study of Inhibition on Lactation in Fluorosis Rats” (article in Chinese), Sheng Li Xue Bao (Acta Physiologica Sinica) 43, no. 5 (1991): 512–17.

B. E. Hawes, J. E. Marzen, S. B. Waters, and P. M. Conn, “Sodium Fluoride Provokes Gonadotrope Desensitization to Gonadotropin-Releasing Hormone (GnRH) and Gonadotrope Sensitization to A23187: Evidence for Multiple G Proteins in GnRH Action,” Endocrinology 130, no. 5 (1992): 2465–75.

A. Shashi, “Studies on Alterations in Brain Lipid Metabolism Following Experimental Fluorosis,” Fluoride 25, no. 2 (1992): 77–84, http://fluoridealert.org/re/shashi-1992.pdf

T. J. Shafer, W. R. Mundy, and H. Tilson, “Aluminum Decreases Muscarinic, Adrenergic, and Metabotropic Receptor-Stimulated Phosphoinositide Hydrolysis in Hippocampal and Cortical Slices from Rat Brain,” Brain Research 629, no. 1 (1993): 133–40.

B. M. Ross, M. McLaughlin, M. Roberts, et al., “Alterations in the Activity of Adenylate Cyclase and High Affinity GTPase in Alzheimer’s Disease,” Brain Research 622, no. 1–2 (1993): 35–42.

A. Shashi, J. P. Singh, and S. P. Thapar, “Effect of Long-Term Administration of Fluoride on Levels of Protein, Free Amino Acids and RNA in Rabbit Brain,” Fluoride 27, no. 3 (1994): 155–59, http://fluoridealert.org/re/shashi-1994.pdf

X. L. Zhao, W. H. Gao, and Z. L. Zhao, “Effects of Sodium Fluoride on the Activity of Ca2+Mg(2+)-ATPase in Synaptic Membrane in Rat Brain” (article in Chinese), Zhonghua Yu Fang Yi Xue Za Zhi 28, no. 5 (1994): 264–66.

N. A. Breakwell, T. Behnisch, S. J. Publicover, and K. G. Reymann, “Attenuation of High-Voltage-Activated Ca2+ Current Run-Down in Rat Hippocampal CA1 Pyramidal Cells by NaF,” Experimental Brain Research 106, no. 3 (1995): 505–8.

P. J. Mullenix, P. K. Denbesten, A. Schunior, and W. J. Kernan, “Neurotoxicity of Sodium Fluoride in Rats,” Neurotoxicology and Teratology 17, no. 2 (1995): 169–77.

T. Pushpalatha, M. Srinivas, and P. Sreenivasula Reddy, “Exposure to High Fluoride Concentration in Drinking Water will Affect Spermatogenesis and Steroidogenesis in Male Albino Rats,” Biometals 18, no. 3 (1995): 207–12. Note: sodium fluoride administered orally to adult male rats at a dose level of 4.5 ppm and 9.0 ppm for 75 days caused significant decrease in the body weight, brain index, and testicular index.

X. Li, L. Song, and R. S. Jope, “Cholinergic Stimulation of AP-1 and NF Kappa B Transcription Factors Is Differentially Sensitive to Oxidative Stress in SH-SY5Y Neuroblastoma: Relationship to Phosphoinositide Hydrolysis,” The Journal of Neuroscience 16, no. 19 (1996): 5914–22.

V. V. Frolkis, S. A. Tanin, and Y. N. Gorban, “Age-Related Changes in Axonal Transport,” Experimental Gerontology 32, no. 4–5 (1997): 441–50.

Z. Z. Guan, Y. Wang, and K. Xiao, “Influence of Experimental Fluorosis on Phospholipid Content and Fatty Acid Composition in Rat Brain” (article in Chinese), Zhonghua Yi Xue Za Zhi 77, no. 8 (1997): 592–96.

R. L. Isaacson, J. A. Varner, and K. F. Jensen, “Toxin-Induced Blood Vessel Inclusions Caused by the Chronic Administration of Aluminum and Sodium Fluoride and Their Implications for Dementia,” Annals of the New York Academy of Sciences 825 (1997): 152–66.

E. T. Koh and S. L. Clarke, “Effects of Fluoride and Aluminum Exposure to Dams Prior to and During Gestation on Mineral Compositions of Bone and Selected Soft Tissues of Female Mice Dams and Pups,” FASEB Journal 11, no. 3 (1997): A406.

Y. Wang, Z. Guan, and K. Xiao, “Changes of Coenzyme Q Content in Brain Tissues of Rats with Fluorosis” (article in Chinese), Zhonghua Yu Fang Yi Xue Za Zhi 31, no. 6 (1997): 330–33.

Z. Z. Guan, Y. N. Wang, K. Q. Xiao, et al., “Influence of Chronic Fluorosis on Membrane Lipids in Rat Brain,” Neurotoxicology and Teratology 20, no. 5 (1998): 537–42.

V. Paul, P. Ekambaram, and A. R. Jayakumar, “Effects of Sodium Fluoride on Locomotor Behavior and a Few Biochemical Parameters in Rats,” Environmental Toxicology and Pharmacology 6, no. 3 (1998): 187–91.

S. A. Plesneva, N. N. Nalivaeva, and I. A. Zhuravin, “Adenylate Cyclase System of the Rat Striatum: Regulatory Properties and the Effects of Gangliosides,” Neuroscience and Behavioral Physiology 28, no. 4 (1998): 392–96.

J. A. Varner, K. F. Jensen, W. Horvath, and R. L. Isaacson, “Chronic Administration of Aluminum-Fluoride or Sodium-Fluoride to Rats in Drinking Water: Alterations in Neuronal and Cerebrovascular Integrity,” Brain Research 784, no. 1–2 (1998): 284–98; extended excerpts at http://www.fluoride-journal.com/98-31-2/31291-95.htm

X. L. Zhao and J. H. Wu, “Actions of Sodium Fluoride on Acetylcholinesterase Activities in Rats,” Biomedical and Environmental Sciences 11, no. 1 (1998): 1–6.

S. Bolea, E. Avignone, N. Berretta, et al., “Glutamate Controls the Induction of GABA-Mediated Giant Depolarizing Potentials Through AMPA Receptors in Neonatal Rat Hippocampal Slices,” Journal of Neurophysiology 81, no. 5 (1999): 2095–102.

E. Sarri and E. Claro, “Fluoride-Induced Depletion of Polyphosphoinositides in Rat Brain Cortical Slices: A Rationale for the Inhibitory Effects on Phospholipase C,” International Journal of Developmental Neuroscience 17, no. 4 (1999): 357–67.

G. B. van der Voet, O. Schijns, and F. A. de Wolff, “Fluoride Enhances the Effect of Aluminium Chloride on Interconnections Between Aggregates of Hippocampal Neurons,” Archives of Physiology and Biochemistry 107, no. 1 (1999): 15–21.

C. Zhang, B. Ling, J. Liu, and G. Wang, “Effect of Fluoride-Arsenic Exposure on the Neurobehavioral Development of Rats Offspring” (article in Chinese), Wei Sheng Yan Jiu 28, no. 6 (1999): 337–38.

J. Chen, X. Chen, and K. Yang, “Effects of Selenium and Zinc on the DNA Damage Caused by Fluoride in Pallium Neural Cells of Rats” (article in Chinese), Wei Sheng Yan Jiu 29, no. 4 (2000): 216–17.

X. H. Lu, G. S. Li, and B. Sun, “Study of the Mechanism of Neurone Apoptosis in Rats from the Chronic Fluorosis,” Chinese Journal of Endemiology 19, no. 2 (2000): 96–98 (as abstracted in Fluoride 34, no. 1 (2001): 82).

Q. Shao, Y. Wang, and Z. Guan, “Influence of Free Radical Inducer on the Level of Oxidative Stress in Brain of Rats with Fluorosis” (article in Chinese), Zhonghua Yu Fang Yi Xue Za Zhi 34, no. 6 (2000): 330–32.

M. L. Vani and K. P. Reddy, “Effects of Fluoride Accumulation on Some Enzymes of Brain and Gastrocnemius Muscle of Mice,” Fluoride 33, no. 1 (2000): 17–26, http://www.fluorideresearch.org/331/files/FJ2000_v33_n1_p17-26.pdf

Y. M. Shivarajashankara, A. R. Shivashankara, P. G. Bhat, et al., “Effect of Fluoride Intoxication on Lipid Peroxidation and Antitoxidant Systems in Rats,” Fluoride 34, no. 2 (2001): 108–13, http://www.fluorideresearch.org/342/files/FJ2001_v34_n2_p108-113.pdf

M. Trabelsi, F. Guermazi, and N. Najiba Zeghal, “Effect of Fluoride on Thyroid Function and Cerebellar Development in Mice,” Fluoride 34, no. 3 (2001): 165–73, http://www.fluoride-journal.com/01-34-3/343-165.pdf

Z. Zhang, X. Shen, and X. Xu, “Effects of Selenium on the Damage of Learning-Memory Ability of Mice Induced by Fluoride” (article in Chinese), Wei Sheng Yan Jiu 30, no. 3 (2001): 144–46.

M. Bhatnagar, P. Rao, J. Sushma, and R. Bhatnagar, “Neurotoxicity of Fluoride: Neurodegeneration in Hippocampus of Female Mice,” Indian Journal of Experimental Biology 40, no. 5 (2002): 546–54.

J. Chen, X. Chen, K. Yang, et al., “Studies on DNA Damage and Apoptosis in Rat Brain Induced by Fluoride” (article in Chinese), Zhonghua Yu Fang Yi Xue Za Zhi 36, no. 4 (2002): 222–24.

I. Ihnatovych, J. Novotny, R. Haugyicoya, et al., “Ontogenetic Development of the G Protein-Mediated Adenylyl Cyclase Signalling in Rat Brain,” Brain Research: Developmental Brain Research 133, no. 1 (2002): 69–75.

Y. G. Long, Y. N. Wang, J. Chen, et al., “Chronic Fluoride Toxicity Decreases the Number of Nicotinic Acetylcholine Receptors in Rat Brain,” Neurotoxicology and Teratology 24, no. 6 (2002): 751–57.

Y. M. Shivarajashankara, A. R. Shivashankara, and P. G. Bhat, et al., “Histological Changes in the Brain of Young Fluoride-Intoxicated Rats,” Fluoride 35, no. 1 (2002): 12–21, http://www.fluorideresearch.org/351/files/FJ2002_v35_n1_p12-21.pdf

Y. M. Shivarajashankara, A. R. Shivashankara, P. G. Bhat, and S. H. Rao, “Brain Lipid Peroxidation and Antioxidant Systems of Young Rats in Chronic Fluoride Intoxication,” Fluoride 35, no. 3 (2002): 197–203, http://www.fluoride-journal.com/02-35-3/353-197.pdf

J. Chen, K. R. Shan, Y. G. Long, et al., “Selective Decreases of Nicotinic Acetylcholine Receptors in PC12 Cells Exposed to Fluoride,” Toxicology 183, no. 1–3 (2003): 235–42.

I. Inkielewicz and J. Krechniak, “Fluoride Content in Soft Tissues and Urine of Rats Exposed to Sodium Fluoride in Drinking Water,” Fluoride 36, no. 4 (2003): 263–66, http://www.fluoride-journal.com/03-36-4/364-263.pdf

A. Shashi, “Histopathological Investigation of Fluoride-Induced Neurotoxicity in Rabbits,” Fluoride 36, no. 2 (2003): 95–105, http://www.fluorideresearch.org/362/files/FJ2003_v36_n2_p95-105.pdf

J. X. Zhai, Z. Y. Guo, C. L. Hu, et al., “Studies on Fluoride Concentration and Cholinesterase Activity in Rat Hippocampus” (article in Chinese), Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 21, no. 2 (2003): 102–4.

P. G. Borasio, F. Cervellati, B. Pavan, and M. C. Pareschi, “‘Low’ Concentrations of Sodium Fluoride Inhibit Neurotransmitter Release from the Guinea-Pig Superior Cervical Ganglion,” Neuroscience Letters 364, no. 2 (2004): 86–89.

A. Lubkowska, D. Chlubek, A. Machoy-Mokrzy´nska, et al., “Concentrations of Fluorine, Aluminum and Magnesium in Some Structures of the Central Nervous System of Rats Exposed to Aluminum and Fluorine in Drinking Water” (article in Polish), Annales Academiae Medicae Stetinensis 50, suppl. 1 (2004): 73–76.

K. R. Shan, X.L. Qi, Y. G. Long, A. Nordberg, and Z. Z. Guan, “Decreased Nicotinic Receptors in PC12 Cells and Rat Brains Influenced by Fluoride Toxicity—a Mechanism Relating to a Damage at the Level in Post-Transcription of the Receptor Genes,” Toxicology 200, no. 2–3 (2004): 169–77.

X. Shen, Z. Zhang, and X. Xu, “Influence of Combined Iodine and Fluoride on Phospholipid and Fatty Acid Composition in Brain Cells of Rats” (article in Chinese), Wei Sheng Yan Jiu 33, no. 2 (2004): 158–61.

Y. Ge, H. Ning, S. Wang, and J. Wang, “Comet Assay of DNA Damage in Brain Cells of Adult Rats Exposed to High Fluoride and Low Iodine,” Fluoride 38, no. 3 (2005): 209–14, http://www.fluorideresearch.org/383/files/383209-214.pdf

J. Krechniak and I. Inkielewicz, “Correlations Between Fluoride Concentration and Free Radical Parameters in Soft Tissues of Rats,” Fluoride 38, no. 4 (2005): 293–96, http://www.fluorideresearch.org/384/files/384293-296.pdf

M. Tsunoda, Y. Aizawa, K. Nakano, et al., “Changes in Fluoride Levels in the Liver, Kidney, and Brain and in Neurotransmitters of Mice after Subacute Administration of Fluorides,” Fluoride 38, no. 4 (2005): 284–92, http://www.fluorideresearch.org/384/files/384284-292.pdf

M. Bhatnagar, P. Rao, A. Saxena, et al., “Biochemical Changes in Brain and Other Tissues of Young Adult Female Mice from Fluoride in their Drinking Water,” Fluoride 39, no. 4 (2006): 280–84, http://www.fluorideresearch.org/394/files/FJ2006_v39_n4_p280-284.pdf

Y. Ge, H. Ning, C. Feng, et al., “Apoptosis in Brain Cells of Offspring Rats Exposed to High Fluoride and Low Iodine,” Fluoride 39, no. 3 (2006): 173–78, http://www.fluorideresearch.org/393/files/FJ2006_v39_n3_p173-178.pdf

I. Bera, R. Sabatini, P. Auteri, et al., “Neurofunctional Effects of Developmental Sodium Fluoride Exposure in Rats,” European Review for Medical and Pharmacological Sciences 11, no. 44 (2007): 211–24.

K. Chirumari and P. K. Reddy, “Dose-Dependent Effects of Fluoride on Neurochemical Milieu in the Hippocampus and Neocortex of Rat Brain,” Fluoride 40, no. 2 (2007): 101–10, http://www.fluorideresearch.org/402/files/FJ2007_v40_n2_p101-110.pdf

T. Xia, M. Zhang, W. H. He, et al., “Effects of Fluoride on Neural Cell Adhesion Molecules mRNA and Protein Expression Levels in Primary Rat Hippocampal Neurons” (article in Chinese), Zhonghua Yu Fang Yi Xue Za Zhi 41, no. 6 (2007): 475–78.

M. Zhang, A. Wang, W. He, et al., “Effects of Fluoride on the Expression of NCAM, Oxidative Stress, and Apoptosis in Primary Cultured Hippocampal Neurons,” Toxicology 236, no. 3 (2007): 208–16.

L. R. Chioca, I. M. Raupp, C. Da Cunha, et al., “Subchronic Fluoride Intake Induces Impairment in Habituation and Active Avoidance Tasks in Rats,” European Journal of Pharmacology 579, no. 1–3 (2008): 196–201.

S. Chouhan and S. J. Flora, “Effects of Fluoride on the Tissue Oxidative Stress and Apoptosis in Rats: Biochemical Assays Supported by IR Spectroscopy Data,” Toxicology 254, no. 1–2 (2008): 61–67.

Q. Gao, Y. J. Liu, and Z. Z. Guan, “Oxidative Stress Might Be a Mechanism Connected with the Decreased ?7 Nicotinic Receptor Influenced by High-Concentration of Fluoride in SH-SY5Y Neuroblastoma Cells,” Toxicology in Vitro 22, no. 4 (2008): 837–43. (Corrigendum in Toxicology in Vitro 22 [2008]: 1814. The concentrations of fluoride should have been given as mM, instead of μM.)

Y. Li, X. Li, and S. Wei, “Effects of High Fluoride Intake on Child Mental Work Capacity: Preliminary Investigation into Mechanisms Involved,” Fluoride 41, no. 4 (2008): 331-5 (originally published in 1994 in The Journal of West China University of Medical Sciences), http://www.fluorideresearch.org/414/files/FJ2008_v41_n4_p331-335.pdf

R. Niu, Z. Sun, J. Wang, Z. Cheng, and J. Wang, “Effects of Fluoride and Lead on Locomotor Behavior and Expression of Nissl Body in Brain of Adult Rats,” Fluoride 41, no. 4 (2008): 276–82, http://www.fluorideresearch.org/414/files/FJ2008_v41_n4_p276-282.pdf

Z. R. Sun, F. Liu, L. Wu, et al., “Effects of High Fluoride Drinking Water on the Cerebral Functions of Mice,” Fluoride 41, no. 2 (2008): 148–51 (originally published in 2000 in the Chinese Journal of Epidemiology), http://www.fluorideresearch.org/412/files/FJ2008_v41_n2_p148-151.pdf

N. Wu, Z. Zhao, W. Gao, and X. Li, “Behavioral Teratology in Rats exposed to Fluoride,” Fluoride 41, no. 2 (2008): 129–133 (originally published in 1995 in Chinese Journal of Control of Endemic Diseases), http://www.fluorideresearch.org/412/files/FJ2008_v41_n2_p129-133.pdf

M. Zhang, A. Wang, T. Xia, and P. He, “Effects of Fluoride on DNA Damage, S-phase Cell-cycle Arrest and the Expression of NF-KappaB in Primary Cultured Rat Hippocampal Neurons,” Toxicology Letters 179, no. 1 (2008): 1–5.

Z. Zhang, X. Xu, X. Shen, and X. Xu, “Effect of Fluoride Exposure on Synaptic Structure of Brain Areas Related to Learning-memory in Mice,” Fluoride 41, no. 2 (2008): 139–43 (originally published in 1999 in Journal of Hygiene Research [China]), http://www.fluorideresearch.org/412/files/FJ2008_v41_n2_p139-143.pdf

V. K. Bharti and R. S. Srivastava, “Fluoride-induced Oxidative Stress in Rat’s Brain and Its Amelioration by Buffalo (Bubalus Bubalis) Pineal Proteins and Melatonin,” Biological Trace Element Research 130, no. 2 (2009): 131–40.

S. J. Flora, M. Mittal, and D. Mishra, “Co-exposure to Arsenic and Fluoride on Oxidative Stress, Glutathione Linked Enzymes, Biogenic Amines and DNA Damage in Mouse Brain,” Journal of the Neurological Sciences 285, no. 1–2 (2009): 198–205.

Q. Gao, Y. J. Liu, and Z. Z. Guan, “Decreased Learning and Memory Ability in Rats with Fluorosis: Increased Oxidative Stress and Reduced Cholinesterase Activity,” Fluoride 42, no. 4 (2009): 277–85, http://www.fluorideresearch.org/424/files/FJ2009_v42_n4_p277-285.pdf

E. A. García-Montalvo, H. Reyes-Pérez, and L. M. Del Razo, “Fluoride Exposure Impairs Glucose Tolerance Via Decreased Insulin Expression and Oxidative Stress,” Toxicology 263 (2009): 75–83. According to the authors, “Interestingly, values of F− in soft rat tissues (kidney, liver, brain and testis) were similar to those in urine (312 μmoll−1). According to this information, urinary F− level is a good indicator of the F− concentration in soft tissues. In cases of subchronic exposure, the level of F− in the plasma probably does not reflect the levels of F− distributed in soft tissues.”

T. Kaur, R. K. Bijarnia, and B. Nehru, “Effect of Concurrent Chronic Exposure of Fluoride and Aluminum on Rat Brain,” Drug and Chemical Toxicology 32, no. 3 (2009): 215–21.

N. Madhusudhan, P. M. Basha, S. Begum, and F. Ahmed, “Fluoride-induced Neuronal Oxidative Stress Amelioration by Antioxidants in Developing Rats,” Fluoride 42, no. 3 (2009): 179–87, http://www.fluorideresearch.org/423/files/FJ2009_v42_n3_p179-187.pdf

R. Niu, Z. Sun, Z. Cheng, Z. Li, and J. Wang, “Decreased Learning Ability and Low Hippocampus Glutamate in Offspring Rats Exposed to Fluoride and Lead,” Environmental Toxicology and Pharmacology 28 (2009): 254–58.

M. Pereira, P. A. Dombrowski, E. M. Losso, et al., “Memory Impairment Induced by Sodium Fluoride Is Associated with Changes in Brain Monoamine Levels, Neurotoxicity Research, December 2009 (in press).

B. P. Wann, B. D’Anjou, T. M. Bah, et al., “Effect of Olfactory Bulbectomy on Adenylyl Cyclase Activity in the Limbic System,” Brain Research Bulletin 79, no. 1 (2009): 32–36.

G. M. Whitford, J. L. Whitford, and S. H. Hobbs, “Appetitive-based Learning in Rats: Lack of Effect of Chronic Exposure to Fluoride,” Neurotoxicology and Teratology 31, no. 4 (2009): 210–15. Note: This study reported “no significant effect on appetitive-based learning.”

P. M. Basha and N. Madhusudhan, “Pre and Post Natal Exposure of Fluoride Induced Oxidative Macromolecular Alterations in Developing Central Nervous System of Rat and Amelioration by Antioxidants,” Neurochemical Research, March 2010: 1017–28.

H. Bouaziz, I. Ben Amara, M. Essefi, F. Croute, and N. Zeghal, “Fluoride-Induced Brain Damages in Suckling Mice,” Pesticide Biochemistry and Physiology 96 (2010): 24–29.

S. Chouhan, V. Lomash, and S. J. Flora, “Fluoride-induced Changes in Haem Biosynthesis Pathway, Neurological Variables and Tissue Histopathology of Rats,” Journal of Applied Toxicology 30, no. 1 (2010): 63–73.

Y. Ge, R. Niu, J. Zhang, and J. Wang, “Proteomic Analysis of Brain Proteins of Rats Exposed to High Fluoride and Low Iodine,” Archives of Toxicology (in press; online April 3, 2010).

C. Z. Gui, L. Y. Ran, J. Li, and Z. Z. Guan, “Changes of Learning and Memory Ability and Brain Nicotinic Receptors of Rat Offspring with Coal Burning Fluorosis,” Neurotoxicology and Teratology (in press; available online April 8, 2010).

H. Kaoud and B. Kalifa, “Effect of Fluoride, Cadmium and Arsenic Intoxication on Brain and Learning-Memory Ability in Rats,” Toxicology Letters 196, suppl. 1 (2010): S53 (abstract from the XII International Congress of Toxicology).

H. Li, H. Huang, Y. Xu, et al., “Toxic Effects of Fluoride on Rat Cerebral Cortex Astrocytes in Vitro” (article in Chinese), Wei Sheng Yan Jiu 39, no. 1 (2010): 86–88.

Y. J. Liu, Q. Gao, C. X. Wu, and Z. Z. Guan, “Alterations of nAChRs and ERK1/2 in the Brains of Rats with Chronic Fluorosis and Their Connections with the Decreased Capacity of Learning and Memory,” Toxicology Letters 192, no. 3 (2010): 324–29.

R. M. M. Sawan, G. A. S. Leite, M. C. P. Saraiva, et al., “Fluoride Increases Lead Concentrations in Whole Blood and in Calcified Tissues from Lead-Exposed Rats,” Toxicology 271, no. 1–2 (2010): 21–26.

J. Zhang, W. J. Zhu, X. H. Xu, and Z. G. Zhang, “Effect of Fluoride on Calcium Ion Concentration and Expression of Nuclear Transcription Factor Kappa-B Rho65 in Rat Hippocampus,” Experimental and Toxicologic Pathology (in press; available online March 19, 2010).

W. Zhu, J. Zhang, and Z. Zhang, “Effects of Fluoride on Synaptic Membrane Fluidity and PSD-95 Expression Level in Rat Hippocampus,” Biological Trace Element Research (in press; available online March 9, 2010).

Fluoride and Bone

Clinical trials on the treatment of osteoporosis with sodium fluoride

T. A. Bayley, J. E. Harrison, T. M. Murray, et al., “Fluoride-Induced Fractures: Relation to Osteogenic Effect,” Journal of Bone and Mineral Research 5, suppl. 1 (1990): S217–22.

M. A. Dambacher, J. Ittner, and P. Ruegsegger, “Long-Term Fluoride Therapy of Postmenopausal Osteoporosis,” Bone 7, no. 3 (1986): 199–205.

J. C. Gerster, S. A. Charhon, P. Jaeger, et al., “Bilateral Fractures of Femoral Neck in Patients with Moderate Renal Failure Receiving Fluoride for Spinal Osteoporosis,” British Medical Journal (Clinical Research Edition) 287, no. 6394 (1983): 723–25.

D. H. Gutteridge, R. I. Price, G. N. Kent, et al., “Spontaneous Hip Fractures in Fluoride-Treated Patients: Potential Causative Factors,” Journal of Bone and Mineral Research 5, suppl. 1 (1990): S205–15.

D. H. Gutteridge, G. O. Stewart, R. L. Prince, et al., “A Randomized Trial of Sodium Fluoride (60 mg) +/- Estrogen in Postmenopausal Osteoporotic Vertebral Fractures: Increased Vertebral Fractures and Peripheral Bone Loss with Sodium Fluoride; Concurrent Estrogen Prevents Peripheral Loss, but Not Vertebral Fractures,” Osteoporosis International 13, no. 2 (2002): 158–70.

L. R. Hedlund and J. C. Gallagher, “Increased Incidence of Hip Fracture in Osteoporotic Women Treated with Sodium Fluoride,” Journal of Bone and Mineral Research 4, no. 2 (1989): 223–25.

J. Inkovaara, R. Heikinheimo, K. Jarvinen, et al., “Prophylactic Fluoride Treatment and Aged Bones,” British Medical Journal 3, no. 5975 (1975): 73–4.

J. D. O’Duffy, H. W. Wahner, W. M. O’Fallon, et al., “Mechanism of Acute Lower Extremity Pain Syndrome in Fluoride-Treated Osteoporotic Patients,” American Journal of Medicine 80, no. 4 (1986): 561–66.

P. Orcel, M. C. de Vernejoul, A. Prier, et al., “Stress Fractures of the Lower Limbs in Osteoporotic Patients Treated with Fluoride,” Journal of Bone and Mineral Research 5, suppl. 1 (1990): S191–94.

B. L. Riggs, S. F. Hodgson, W. M. O’Fallon, et al., “Effect of Fluoride Treatment on the Fracture Rate in Post-Menopausal Women with Osteoporosis,” New England Journal of Medicine 322, no. 12 (1990): 802–9.

C. M. Schnitzler, J. R. Wing, K. A. Gear, and H. J. Robson, “Bone Fragility of the Peripheral Skeleton during Fluoride Therapy for Osteoporosis,” Clinical Orthopaedics no. 261 (1990): 268–75.

Animal studies showing fluoride weakens bones

D. F. Beary, “The Effects of Fluoride and Low Calcium on the Physical Properties of the Rat Femur,” The Anatomical Record 164, no. 3 (1969): 305–16.

A. Bohatyrewicz, “Bone Fluoride in Proximal Femur Fractures,” Fluoride 34, no. 4 (2001): 227–35, http://www.fluorideresearch.org/344/files/FJ2001_v34_n4_p227-235.pdf

A. Bohatyrewicz, “Effects of Fluoride on Mechanical Properties of Femoral Bone in Growing Rats,” Fluoride 32, no. 2 (1999): 47–54, http://fluoridealert.org/re/bohatyrewicz-1999.pdf

T. W. Burnell, E. R. Peo Jr., A. J. Lewis, and J. D. Crenshaw, “Effect of Dietary Fluorine on Growth, Blood and Bone Characteristics of Growing-Finishing Pigs,” Journal of Animal Science 63, no. 6 (1986): 2053–67.

M. M. Chan, R. B. Rucker, F. Zeman, and R. S. Riggins, “Effect of Fluoride on Bone Formation and Strength in Japanese Quail,” Journal of Nutrition 103, no. 10 (1973): 1431–40.

I. Gedalia, A. Frumkin, and H. Zukerman, “Effects of Estrogen on Bone Composition in Rats at Low and High Fluoride Intake,” Endocrinology 75 (1964): 201–5.

M. H. Lafage, R. Balena, M. A. Battle, et al., “Comparison of Alendronate and Sodium Fluoride Effects on Cancellous and Cortical Bone in Minipigs. A One-Year Study,” The Journal of Clinical Investigation 95, no. 5 (1995): 2127–33.

L. Mosekilde, J. Kragstrup, and A. Richards, “Compressive Strength, Ash Weight, and Volume of Vertebral Trabecular Bone in Experimental Fluorosis in Pigs,” Calcified Tissue International 40, no. 6 (1987): 318–22.

R. S. Riggins, R. C. Rucker, M. M. Chan, et al., “The Effect of Fluoride Supplementation on the Strength of Osteopenic Bone,” Clinical Orthopaedics, no. 114 (1976): 352–57.

R. S. Riggins, F. Zeman, and D. Moon, “The Effects of Sodium Fluoride on Bone Breaking Strength,” Calcified Tissue Research 14, no. 4 (1974): 283–89.

J. C. Robin, B. Schepart, H. Calkins, et al., “Studies on Osteoporosis III. Effect of Estrogens and Fluoride,” Journal of Medicine 11, no. 1 (1980): 1–14.

H. Roeckert, “X-ray Absorption and X-ray Fluorescence Micro-Analyses of Mineralized Tissue of Rats Which Have Ingested Fluoridated Water,” Acta Pathologica et Microbiologica Scandinavica 59 (1963): 32–38.

H. Roeckert and H. Sunzel, “Skeletal Lesions Following Ingestion of Fluoridated Water,” Experientia 15 (1960): 155–56.

C. H. Søgaard, L. Mosekilde, W. Schwartz, et al., “Effects of Fluoride on Rat Vertebral Body Biomechanical Competence and Bone Mass,” Bone 16, no. 1 (1995): 163–9.

C. H. Turner, M. P. Akhter, and R. P. Heaney, “The Effects of Fluoridated Water on Bone Strength,” Journal of Orthopaedic Research 10, no. 4 (1992): 581–87.

C. H. Turner and A. J. Dunipace, “On Fluoride and Bone Strength” (letter), Calcified Tissue International 53, no. 4 (1993): 289–90.

C. H. Turner, L. P. Garetto, A. J. Dunipace, et al., “Fluoride Treatment Increased Serum IGF-1, Bone Turnover, and Bone Mass, But Not Bone Strength, in Rabbits,” Calcified Tissue International 61, no. 1 (1997): 77–83.

C. H. Turner, K. Hasegawa, W. Zhang, et al., “Fluoride Reduces Bone Strength in Older Rats,” Journal of Dental Research 74, no. 8 (1995): 1475–81, http://jdr.sagepub.com/cgi/reprint/74/8/1475

C. H. Turner, W. R. Hinckley, M. E. Wilson, et al., “Combined Effects of Diets with Reduced Calcium and Phosphate and Increased Fluoride Intake on Vertebral Bone Strength and Histology in Rats,” Calcified Tissue International 69, no. 1 (2001): 51–57.

C. H. Turner, I. Owan, E. J. Brizendine, et al., “High Fluoride Intakes Cause Osteomalacia and Diminished Bone Strength in Rats with Renal Deficiency,” Bone 19, no. 6 (1996): 595–601.

B. Uslu, “Effect of Fluoride on Collagen Synthesis in the Rat,” Research and Experimental Medicine 182, no. 1 (1983): 7–12.

I. Wolinsky, A. Simkin, and K. Guggenheim, “Effects of Fluoride on Metabolism and Mechanical Properties of Rat Bone,” American Journal of Physiology 223, no. 1 (1972): 46–50.

Nineteen studies on the possible association of hip fracture and fluoridated water published since 1990

Studies reporting an association between fluoridated water (1 ppm fluoride) and hip fracture

C. Cooper, C. Wickham, R. F. Lacey, and D. J. Barker, “Water Fluoride Concentration and Fracture of the Proximal Femur,” Journal of Epidemiology and Community Health 44, no. 1 (1990): 17–19; and C. Cooper, C. A. Wickham, D. J. Barker, and S. J. Jacobsen, “Water Fluoridation and Hip Fracture” (letter, a reanalysis of data presented in 1990 paper), Journal of the American Medical Association 266, no. 4 (1990): 513–14.

C. Danielson, J. L. Lyon, M. Egger, and G. K. Goodenough, “Hip Fractures and Fluoridation in Utah’s Elderly Population,” Journal of the American Medical Association 268, no. 6 (1992): 746–48.

K. T. Hegmann et al., “The Effects of Fluoridation on Degenerative Joint Disease (DJD) and Hip Fractures,” abstract no. 71 of the 33rd Annual Meeting of the Society for Epidemiological Research, June 15–17, 2000, published in a supplement of American Journal of Epidemiology (2000): P S18.

S. J. Jacobsen, J. Goldberg, C. Cooper, and S. A. Lockwood, “The Association Between Water Fluoridation and Hip Fracture Among White Women and Men Aged 65 Years and Older. A National Ecologic Study,” Annals of Epidemiology 2, no. 5 (1992): 617–26.

S. J. Jacobsen, J. Goldberg, T. P. Miles, et al., “Regional Variation in the Incidence of Hip Fracture. US White Women Aged 65 Years and Older,” Journal of the American Medical Association 264, no. 4 (1990): 500–502.

H. Jacqmin-Gadda, D. Commenges, and J. F. Dartigues, “Fluorine Concentration in Drinking Water and Fractures in the Elderly” (letter), Journal of the American Medical Association 273, no. 10 (1995): 775–76.

H. Jacqmin-Gadda, A. Fourrier, D. Commenges, and J. F. Dartigues, “Risk Factors for Fractures in the Elderly,” Epidemiology 9, no. 4 (1998): 417–23. (An elaboration of the 1995 study referred to in the JAMA letter.)

C. Keller, “Fluorides in Drinking Water” (unpublished results), discussed in S. L. Gordon and S. B. Corbin “Summary of Workshop on Drinking Water Fluoride Influence on Hip Fracture on Bone Health,” Osteoporosis International 2 (1992): 109–17.

P. Kurttio, N. Gustavsson, T. Vartiainen, and J. Pekkanen, “Exposure to Natural Fluoride in Well Water and Hip Fracture: A Cohort Analysis in Finland,” American Journal of Epidemiology 150, no. 8 (1999): 817–24.

D. S. May and M. G. Wilson, “Hip Fractures in Relation to Water Fluoridation: An Ecologic Analysis (unpublished data), discussed in S. L. Gordon and S. B. Corbin “Summary of Workshop on Drinking Water Fluoride Influence on Hip Fracture on Bone Health,” Osteoporosis International 2 (1992): 109–17.

Studies reporting an association between water-fluoride levels higher than that of fluoridated water (4 ppm+) and hip fracture

Y. Li, C. Liang, C. W. Slemenda, et al., “Effect of Long-Term Exposure to Fluoride in Drinking Water on Risks of Bone Fractures,” Journal of Bone and Mineral Research 16, no. 5 (2001): 932–39.

M. F. Sowers, M. K. Clark, M. L. Jannausch, and R. B. Wallace, “A Prospective Study of Bone Mineral Content and Fracture in Communities with Differential Fluoride Exposure,” American Journal of Epidemiology 133, no. 7 (1991): 649–60.

Studies reporting no association between water fluoride and hip fracture
Note that in four of these eight studies, an association was found between fluoride and some other form of fracture—e.g. wrist fracture. See notes and
quotes below

J. A. Cauley, P. A. Murphy, T. J. Riley, and A. M. Buhari, “Effects of Fluoridated Drinking Water on Bone Mass and Fractures: The Study of Osteoporotic Fractures,” Journal of Bone and Mineral Research 10, no. 7 (1995): 1076–86.

D. Feskanich, W. Owusu, D. J. Hunter, et al., “Use of Toenail Fluoride Levels as an Indicator for the Risk of Hip and Forearm Fractures in Women,” Epidemiology 9, no. 4 (1998): 412–16. Note: While this study didn’t find an association between water fluoride and hip fracture, it did find an association—albeit not statistically significant 1.6 (0.8–3.1)—between fluoride exposure and elevated rates of forearm fracture.

S. Hillier, C. Cooper, S. Kellingray, et al., “Fluoride in Drinking Water and Risk of Hip Fracture in the UK: A Case Control Study,” The Lancet 335, no. 9200 (2000): 265–69.

S. J. Jacobsen, W. M. O’Fallon, and L. J. Melton III, “Hip Fracture Incidence Before and After the Fluoridation of the Public Water Supply, Rochester, Minnesota,” American Journal of Public Health 83, no. 5 (1993): 743–45, http://ajph.aphapublications.org/cgi/reprint/83/5/743.pdf

M. R. Karagas, J. A. Baron, J. A. Barrett, and S. J. Jacobsen, “Patterns of Fracture Among the United States Elderly: Geographic and Fluoride Effects,” Annals of Epidemiology 6, no. 3 (1996): 209–16. Note: As with Feskanich, et al. (1998), this study didn’t find an association between fluoridation and hip fracture, but it did find an association between fluoridation and distal forearm fracture, as well as proximal humerus fracture. “Independent of geographic effects, men in fluoridated areas had modestly higher rates of fractures of the distal forearm and proximal humerus than did men in nonfluoridated areas.”

R. Lehmann, M. Wapniarz, B. Hofmann, et al., “Drinking Water Fluoridation: Bone Mineral Density and Hip Fracture Incidence,” Bone 22, no. 3 (1998): 273–78.

K. R. Phipps, E. S. Orwoll, J. D. Mason, and J. A Cauley, “Community Water Fluoridation, Bone Mineral Density and Fractures: Prospective Study of Effects in Older Women,” British Medical Journal 321, no. 7265 (2000): 860–64. Note: As with Feskanich, et al. (1998) and Karagas, et al. (1996), this study didn’t find an association between water fluoride and hip fracture, but it did find an association between water fluoride and other types of fracture—in this case, wrist fracture. “There was a non-significant trend toward an increased risk of wrist fracture.”

M. E. Suarez-Almazor, G. Flowerdew, L. D. Saunders, et al., “The Fluoridation of Drinking Water and Hip Fracture Hospitalization Rates in Two Canadian Communities,” American Journal of Public Health 83, no. 5 (1993): 689–93, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1694711/pdf/amjph00529-0067.pdf -Note: While the authors of this study conclude that there is no association between fluoridation and hip fracture, their own data reveals a statistically significant increase in hip fracture for men living in the fluoridated area. According to the authors, “Although a statistically significant increase in the risk of hip fracture was observed among Edmonton men, this increase was relatively small (RR=1.12).”

See also: ENDNOTES

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