Abstract
Purpose of Review
We performed a systematic review and meta-analysis on the relation between fluoride exposure and skeletal fluorosis (SF) using a novel statistical methodology for dose-response modeling.
Recent Findings
Skeletal fluorosis, a major health issue that is endemic in some regions, affects millions of people worldwide. However, data regarding the dose-response relation between fluoride exposure and SF are limited and outdated.
Summary
We included twenty-three studies in the meta-analysis. When comparing the highest versus the lowest fluoride category, the summary risk ratio (RR) for SF prevalence was 2.05 (95% CI 1.60; 2.64), with a value of 2.73 (95% CI 1.92; 3.90) for drinking water and 1.40 (95% CI 0.90; 2.17) for urinary fluoride. The RR by the risk of bias (RoB) was 2.37 (95% CI 1.56; 3.58) and 1.78 (95% CI 1.34; 2.36) for moderate and high RoB studies, respectively. The dose-response curve based on a one-stage cubic spline regression model showed an almost linear positive relation between exposure and SF occurrence starting from relatively low concentrations up to 5 mg/L and 2.5 mg/L, respectively, for water and urinary fluoride, with no substantial increase above this threshold. The RR for developing moderate-severe forms increases at 5.00 mg/L and 2.5 mg/L of water and urinary fluoride, respectively. Better-quality studies are needed to confirm these results, but greater attention should be given to water fluoride levels to prevent SF, in addition to the other potential adverse effects of fluoride exposure.
Similar content being viewed by others
Data Availability
All data generated or analyzed during this study are included in this published article and its supplementary information files.
References
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Whitford GM. Intake and metabolism of fluoride. Adv Dent Res. 1994;8(1):5–14. https://doi.org/10.1177/08959374940080011001.
Urbano T, Zagnoli F, Malavolti M, Halldorsson TI, Vinceti M, Filippini T. Dietary intake of potentially toxic elements and children’s chemical exposure. Curr Opin Environ Sci Health. 2022;30:100393. https://doi.org/10.1016/j.coesh.2022.100393.
O’Shaughnessy KL, Fischer F, Zenclussen AC. Perinatal exposure to endocrine disrupting chemicals and neurodevelopment: how articles of daily use influence the development of our children. Best Pract Res Clin Endocrinol Metab. 2021;35(5):101568. https://doi.org/10.1016/j.beem.2021.101568.
Lorber M, Schecter A, Paepke O, Shropshire W, Christensen K, Birnbaum L. Exposure assessment of adult intake of bisphenol A (BPA) with emphasis on canned food dietary exposures. Environ Int. 2015;77:55–62. https://doi.org/10.1016/j.envint.2015.01.008.
EFSA - European Food Safety Authority. Scientific opinion on dietary reference values for fluoride. EFSA J. 2013;11(8):3332. https://doi.org/10.2903/j.efsa.2013.3332.
National Academies of Sciences, Engineering, and Medicine, Board on Environmental Studies and Toxicology, Division on Earth and Life Studies. Review of the revised NTP monograph on the systematic review of fluoride exposure and neurodevelopmental and cognitive health effects: a letter report. Washington, D.C.: National Academies Press; 2021.
Saldarriaga A, Rojas-Gualdrón D, Restrepo M, Santos-Pinto L, Jeremias F. Dental fluorosis severity in children 8-12 years old and associated factors. Acta Odontol Latinoam. 2021;34(2):156–65. https://doi.org/10.54589/aol.34/2/156.
U.S. Department of Health and Human Services Federal Panel on Community Water Fluoridation. U.S. public health service recommendation for fluoride concentration in drinking water for the prevention of dental caries. Public Health Rep. 2015;130(4):318–31. https://doi.org/10.1177/003335491513000408.
Veneri F, Vinceti M, Generali L, Giannone ME, Mazzoleni E, Birnbaum LS, et al. Fluoride exposure and cognitive neurodevelopment: systematic review and dose-response meta-analysis. Environ Res. 2023;221:115239. https://doi.org/10.1016/j.envres.2023.115239.
Yuan L, Fei W, Jia F, Jun-ping L, Qi L, Fang-ru N, et al. Health risk in children to fluoride exposure in a typical endemic fluorosis area on Loess Plateau, north China, in the last decade. Chemosphere. 2020;243:125451. https://doi.org/10.1016/j.chemosphere.2019.125451.
• Zhou J, Sun D, Wei W. Necessity to pay attention to the effects of low fluoride on human health: an overview of skeletal and non-skeletal damages in epidemiologic investigations and laboratory studies. Biol Trace Elem Res. 2023;201(4):1627–38. https://doi.org/10.1007/s12011-022-03302-7. This article summarizes the harmful effects of lower fluoride levels in drinking water achieved with mitigation programs based on epidemiological studies on the skeletal and nonskeletal health of humans and animals.
Fiore G, Veneri F, Di Lorenzo RD, Generali L, Vinceti M, Filippini T. Fluoride exposure and ADHD: a systematic review of epidemiological studies. Medicina. 2023;59(4):797. https://doi.org/10.3390/medicina59040797.
World Health Organisation. Oral Health - overview, impact, prevention and response. 2021. Available from: https://www.who.int/health-topics/oral-health#tab=tab_2. Accessed 6 Jan 2022.
CDC - Center for Disease Control and Prevention. Community water fluoridation. 2021. Available from: https://www.cdc.gov/fluoridation/index.html?CDC_AA_refVal=https%3A%2F%2F2.gy-118.workers.dev/%3A443%2Fhttps%2Fwww.cdc.gov%2Ffluoridation%2Findex.htm. Accessed 17 Jan 2022.
European Commission. Critical review of any new evidence on the hazard profile, health effects, and human exposure to fluoride and the fluoridating agents of drinking water. 2011.
NIH - National Institute of Health. Fluoride - Fact sheet. 2021. Available from: https://ods.od.nih.gov/factsheets/Fluoride-HealthProfessional/. Accessed 19 Jan 2022.
Marinho VC, Higgins JP, Logan S, Sheiham A. Topical fluoride (toothpastes, mouthrinses, gels or varnishes) for preventing dental caries in children and adolescents. Cochrane Database Syst Rev. 2003; https://doi.org/10.1002/14651858.CD002782.
NHS - National Health System. Fluoride. 2021. Available from: https://www.nhs.uk/conditions/fluoride/. Accessed 19 Jan 2022.
•• Podgorski J, Berg M. Global analysis and prediction of fluoride in groundwater. Nat Commun. 2022;13(1):4232. https://doi.org/10.1038/s41467-022-31940-x. A state-of-the-art global risk assessment for dental and skeletal fluorosis according to fluoride levels in groundwater exceeding 1.5 mg/L, based on a machine learning model.
Fewtrell L, Smith S, Kay D, Bartram J. An attempt to estimate the global burden of disease due to fluoride in drinking water. J Water Health. 2006;4(4):533–42.
• Srivastava S, Flora SJS. Fluoride in drinking water and skeletal fluorosis: a review of the global impact. Curr Envir Health Rpt. 2020;7(2):140–6. https://doi.org/10.1007/s40572-020-00270-9. An interesting recent review on skeletal fluorosis and its prevalence, focusing on endemic areas, also highlighting the role of oxidative stress in skeletal fluorosis pathogenesis and discussing current strategies for managing this disease, including fluorosis mitigation programs.
Koroglu BK, Ersoy IH, Koroglu M, Balkarli A, Ersoy S, Varol S, et al. Serum parathyroid hormone levels in chronic endemic fluorosis. Biol Trace Elem Res. 2011;143(1):79–86. https://doi.org/10.1007/s12011-010-8847-2.
• Cook FJ, Seagrove-Guffey M, Mumm S, Veis DJ, McAlister WH, Bijanki VN, et al. Non-endemic skeletal fluorosis: causes and associated secondary hyperparathyroidism (case report and literature review). Bone. 2021;145:115839. https://doi.org/10.1016/j.bone.2021.115839. A well-documented case report and interesting review of unusual skeletal fluorosis in non-endemic areas, along with a discussion on the causes and the possible pathogenetic mechanisms.
Whyte MP, Totty WG, Lim VT, Whitford GM. Skeletal fluorosis from instant tea. J Bone Miner Res. 2008;23(5):759–69. https://doi.org/10.1359/jbmr.080101.
•• Qiao L, Liu X, He Y, Zhang J, Huang H, Bian W, et al. Progress of signaling pathways, stress pathways and epigenetics in the pathogenesis of skeletal fluorosis. IJMS. 2021;22(21):11932. https://doi.org/10.3390/ijms222111932. Comprehensive review of the genetic factors and pathogenetic mechanisms of skeletal fluorosis, including signaling and stress pathways and epigenetics.
Environmental Protection Agency (US). Basic information about fluoride in drinking water: review of fluoride drinking water standard. 2015. Available from: http://water.epa.gov/drink/contaminants/basicinformation/fluoride.cfm. Accessed 2 Apr 2023.
National Research Council. Fluoride in drinking water: a scientific review of EPA’s standards. Washington, D.C.: National Academies Press; 2006.
U.S. Environmental Protection Agency (EPA). Fluoride: dose-response analysis for non-cancer effects. 2010.
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;n71 https://doi.org/10.1136/bmj.n71.
Teotia SPS, Teotia M, Singh DP. Bone static and dynamic histomorphometry in endemic skeletal fluorosis. In: Studies in Environmental Science. Elsevier; 1986. p. 347–55.
Morgan RL, Thayer KA, Santesso N, Holloway AC, Blain R, Eftim SE, et al. A risk of bias instrument for non-randomized studies of exposures: a users’ guide to its application in the context of GRADE. Environ Int. 2019;122:168–84. https://doi.org/10.1016/j.envint.2018.11.004.
Pei J, Li B, Liu Y, Liu X, Li M, Chu Y, et al. Matrix metallopeptidase-2 gene rs2287074 polymorphism is associated with brick tea skeletal fluorosis in Tibetans and Kazaks, China. Sci Rep. 2017;7(1):40086. https://doi.org/10.1038/srep40086.
Wen C, Zhang Q, Xie F, Jiang J. Brick tea consumption and its relationship with fluorosis in Tibetan areas. Front Nutr. 2022;9:1030344. https://doi.org/10.3389/fnut.2022.1030344.
Fan Z, Gao Y, Wang W, Gong H, Guo M, Zhao S, et al. Prevalence of brick tea-type fluorosis in the Tibet Autonomous Region. J Epidemiol. 2016;26(2):57–63. https://doi.org/10.2188/jea.JE20150037.
Filippini T, Wise LA, Vinceti M. Cadmium exposure and risk of diabetes and prediabetes: a systematic review and dose-response meta-analysis. Environ Int. 2022;158:106920. https://doi.org/10.1016/j.envint.2021.106920.
Harrell FE. Regression modeling strategies: with applications to linear models, logistic regression, and survival analysis. Springer, New York, NY; 2001.
Orsini N, Spiegelman D. Meta-analysis of dose-response relationships. In: Schmid CH, Stijnen T, White I, editors. Handbook of Meta-Analysis. New York: Chapman and Hall/CRC; 2020.
Orsini N. Weighted mixed-effects dose–response models for tables of correlated contrasts. The Stata Journal. 2021;21(2):320–47. https://doi.org/10.1177/1536867X211025798.
Vinceti M, Filippini T, Wise LA, Rothman KJ. A systematic review and dose-response meta-analysis of exposure to environmental selenium and the risk of type 2 diabetes in nonexperimental studies. Environ Res. 2021;197:111210. https://doi.org/10.1016/j.envres.2021.111210.
•• Villa A, Anabalon M, Zohouri V, Maguire A, Franco AM, Rugg-Gunn A. Relationships between fluoride intake, urinary fluoride excretion and fluoride retention in children and adults: an analysis of available data. Caries Res. 2010;44(1):60–8. https://doi.org/10.1159/000279325. An interesting study providing insight into fluoride metabolism, specifically on the relation between fluoride intake and urinary excretion and retention in adults and children.
Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60. https://doi.org/10.1136/bmj.327.7414.557.
Choubisa SL. Fluoride in drinking water and its toxicosis in tribals of Rajasthan, India. Proc Natl Acad Sci, India, Sect B Biol Sci. 2012;82(2):325–30. https://doi.org/10.1007/s40011-012-0047-8.
Choubisa SL. Chronic fluoride intoxication (fluorosis) in tribes and their domestic animals. Intern J Environ Studies. 1999;56(5):703–16. https://doi.org/10.1080/00207239908711233.
Gitte S, Sabat R, Kamble K. Epidemiological survey of fluorosis in a village of Bastar division of Chhattisgarh state, India. Int J Med Public Health. 2015;5(3):232. https://doi.org/10.4103/2230-8598.161539.
Zhang L, DUAN Y, XIA R, WANG C. Surveillance for endemic fluorosis related with brick tea drinking in Xinjiang, 2009–2012. Dis Surveill. 2014;29(2):143–6. https://doi.org/10.3784/j.issn.1003-9961.2014.02.014.
Abdennebi E, Fandi R, Lamnaouer D. Human fluorosis in Morocco: analytical and clinical investigations. Vet Human Toxicol. 1995;37(5):465–8.
Brouwer ID, De Bruin A, Dirks OB, Hautvast JGAJ. Unsuitability of World Health Organisation guidelines for fluoride concentrations in drinking water in Senegal. The Lancet. 1988;331(8579):223–5. https://doi.org/10.1016/S0140-6736(88)91073-2.
Choubisa S, Choubisa D, Joshi S, Choubisa L. Fluorosis in some tribal villages of Dungarpur district of Rajasthan, India. Fluoride. 1997;30(4):223–8.
Choubisa SL. Endemic fluorosis in southern Rajasthan, India. Fluoride. 2001;34(1):61–70.
Choubisa S, Choubisa L, Choubisa D. Osteo-dental fluorosis in relation to nutritional status, living habits, and occupation in rural tribal areas of Rajasthan, India. Fluoride. 2009;42(3):210–5.
Hussain J, Hussain I, Sharma KC. Fluoride and health hazards: community perception in a fluorotic area of central Rajasthan (India): an arid environment. Environ Monit Assess. 2010;162(1–4):1–14. https://doi.org/10.1007/s10661-009-0771-6.
Jolly SS, Singh BM, Mathur OC, Malhotra KC. Epidemiological, clinical, and biochemical study of endemic dental and skeletal fluorosis in Punjab. BMJ. 1968;4(5628):427–9. https://doi.org/10.1136/bmj.4.5628.427.
Liu G, Ye Q, Chen W, Zhao Z, Li L, Lin P. Study of the relationship between the lifestyle of residents residing in fluorosis endemic areas and adult skeletal fluorosis. Environ Toxicol Pharmacol. 2015;40(1):326–32. https://doi.org/10.1016/j.etap.2015.06.022.
• Liu Y, Yang Y, Wei Y, Liu X, Li B, Chu Y, et al. sKlotho is associated with the severity of brick tea-type skeletal fluorosis in China. Sci Total Environ. 2020;744:140749. https://doi.org/10.1016/j.scitotenv.2020.140749. Serum soluble Klotho (sKlotho) is a protein involved in mineral metabolism and bone development. This study gives an interesting insight into the pathogenetic relation between fluoride exposure, sKlotho levels, skeletal fluorosis, and its severity, concluding that such protein may be a potential mediator of skeletal fluorosis.
Meena C, Dwivedi S, Rathore S, Gonmei Z, Gs T, Bala K, et al. Assessment of skeletal fluorosis among children in two blocks of rural area, Jaipur district, Rajasthan, India. Asian J Pharm Clin Res. 2017;10(9):322. https://doi.org/10.22159/ajpcr.2017.v10i9.19993.
Meghe A, Malpe D, Meshram D. Effect of fluoride contaminated groundwater on human health in fluorosis endemic areas. IJFMT. 2021;15(1):529–34. https://doi.org/10.37506/ijfmt.v15i1.13460.
Mohammadi AA, Yousefi M, Yaseri M, Jalilzadeh M, Mahvi AH. Skeletal fluorosis in relation to drinking water in rural areas of West Azerbaijan, Iran. Sci Rep. 2017;7(1):17300. https://doi.org/10.1038/s41598-017-17328-8.
Shorter JP, Massawe J, Parry N, Walker RW. Comparison of two village primary schools in northern Tanzania affected by fluorosis. Int Health. 2010;2(4):269–74. https://doi.org/10.1016/j.inhe.2010.09.010.
Shruthi M, Santhuram A, Arun H, Kishore KB. A comparative study of skeletal fluorosis among adults in two study areas of Bangarpet taluk, Kolar. Indian J Public Health. 2016;60(3):203. https://doi.org/10.4103/0019-557X.189014.
Srikanth R, Chandra TR, Kumar BR. Endemic fluorosis in five villages of the Palamau district, Jharkhand, India. Fluoride. 2008;41(3):206–2011.
Wang C, Gao Y, Wang W, Zhao L, Zhang W, Han H, et al. A national cross-sectional study on effects of fluoride-safe water supply on the prevalence of fluorosis in China. BMJ Open. 2012;2(5):e001564. https://doi.org/10.1136/bmjopen-2012-001564.
Wu J, Qin M, Li D, Yang D, Li B, Liu X, et al. Correlation analysis of urinary fluoride levels and the daily intake of fluoride in brick tea type fluorosis areas. Fluoride. 2016;49(4 pt.1):449–57.
Xiang Q, Chen L, Chen X, Wang C, Liang Y, Liao Q, et al. Serum fluoride and skeletal fluorosis in two villages in Jiangsu province, China. Fluoride. 2005;38(3):178–84.
World Health Organization. Fluorides and human health. WHO; 1970.
Ministry of Health of the People’s Republic of China. WS 192-2008 - Diagnostic Criteria for Endemic Skeletal Fluorosis. 2008.
World Health Organization. Fluorine and fluorides. WHO; 1984.
Teotia S, Teotia M, Singh K. Highlights of forty years of research on endemic skeletal fluorosis in India. In: 4th International workshop on fluorosis Prevention and Defluoridation of water. Thailand: ISFR, EnDeCo & ICOH; 2004. p. 107–125.
Susheela AK, India. Department of Family Welfare, World Health Organization. Country Office for India. Fluorosis: an easily preventable disease through practice of interventions. In: Doctor’s Handbook: for Doctors Functioning in All Health Delivery Outlets in Endemic Districts in India. New Delhi: Fluorosis Research & Rural Development Foundation; 2005. p. 1–21.
Ayoob S, Gupta AK. Fluoride in drinking water: a review on the status and stress effects. Crit Rev Environ Sci Technol. 2006;36(6):433–87. https://doi.org/10.1080/10643380600678112.
Christie DP. The spectrum of radiographic bone changes in children with fluorosis. Radiology. 1980;136(1):85–90. https://doi.org/10.1148/radiology.136.1.7384528.
Ministry of Health of the People’s Republic of China. GB 17018-2011 - China National Standard for division of endemic fluorosis areas. 2012.
Ando M, Tadano M, Yamamoto S, Tamura K, Asanuma S, Watanabe T, et al. Health effects of fluoride pollution caused by coal burning. Sci Total Environ. 2001;271(1–3):107–16. https://doi.org/10.1016/s0048-9697(00)00836-6.
Cao J, Zhao Y, Liu J, Xirao R, Danzeng S, Daji D, et al. Brick tea fluoride as a main source of adult fluorosis. Food Chem Toxicol. 2003;41(4):535–42. https://doi.org/10.1016/s0278-6915(02)00285-5.
Izuora K, Twombly JG, Whitford GM, Demertzis J, Pacifici R, Whyte MP. Skeletal fluorosis from brewed tea. J Clin Endocrinol Metab. 2011;96(8):2318–24. https://doi.org/10.1210/jc.2010-2891.
Jaganmohan P, Narayana S, Sambasiva R. Prevalence of high fluoride concentration in drinking water in Nellore district, Anadra Pradesh, India: a biochemical study to develop the relation to the renal failures. World J Med Sci. 2010;5(2):45–8.
Tefera N, Mulualem D, Baye K, Tessema M, Woldeyohannes M, Yehualashet A, et al. Association between dietary fluoride and calcium intake of school-age children with symptoms of dental and skeletal fluorosis in Halaba, Southern Ethiopia. Front Oral Health. 2022;3:853719. https://doi.org/10.3389/froh.2022.853719.
Ba Y, Zhang H, Wang G, Wen S, Yang Y, Zhu J, et al. Association of dental fluorosis with polymorphisms of estrogen receptor gene in Chinese children. Biol Trace Elem Res. 2011;143(1):87–96. https://doi.org/10.1007/s12011-010-8848-1.
Jiang M, Mu L, Wang Y, Yan W, Jiao Y. The relationship between Alu I polymorphisms in the calcitonin receptor gene and fluorosis endemic to Chongqing. China. Med Princ Pract. 2015;24(1):80–3. https://doi.org/10.1159/000368435.
Xu S, Khoo S, Dang A, Witt S, Do V, Zhen E, et al. Differential regulation of mitogen-activated protein/ERK kinase (MEK)1 and MEK2 and activation by a ras-independent mechanism. Mol Endocrinol. 1997;11(11):1618–25. https://doi.org/10.1210/mend.11.11.0010.
Varol E, Icli A, Aksoy F, Bas HA, Sutcu R, Ersoy IH, et al. Evaluation of total oxidative status and total antioxidant capacity in patients with endemic fluorosis. Toxicol Ind Health. 2013;29(2):175–80. https://doi.org/10.1177/0748233711428641.
Wu J, Wang W, Liu Y, Sun J, Ye Y, Li B, et al. Modifying role of GSTP1 polymorphism on the association between tea fluoride exposure and the brick-tea type fluorosis. PLoS One. 2015;10(6):e0128280. https://doi.org/10.1371/journal.pone.0128280.
Li B-Y, Yang Y-M, Liu Y, Sun J, Ye Y, Liu X-N, et al. Prolactin rs1341239 T allele may have protective role against the brick tea type skeletal fluorosis. PLoS One. 2017;12(2):e0171011. https://doi.org/10.1371/journal.pone.0171011.
• Pramanik S, Saha D. The genetic influence in fluorosis. Environ Toxicol Pharmacol. 2017;56:157–62. https://doi.org/10.1016/j.etap.2017.09.008. A recent and comprehensive critical review focusing on the genetic factors and specific polymorphisms involved in fluorosis.
Richards A. Mosekilde Li, Søgaard CH. Normal age-related changes in fluoride content of vertebral trabecular bone—Relation to bone quality. Bone. 1994;15(1):21–6. https://doi.org/10.1016/8756-3282(94)90886-9.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare no competing interests.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the Topical Collection on Methods in Environmental Epidemiology
Supplementary information
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Veneri, F., Iamandii, I., Vinceti, M. et al. Fluoride Exposure and Skeletal Fluorosis: a Systematic Review and Dose-response Meta-analysis. Curr Envir Health Rpt 10, 417–441 (2023). https://doi.org/10.1007/s40572-023-00412-9
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40572-023-00412-9