Research Studies
Study Tracker
Chronic Fluoride Exposure from Brick Tea Consumption Disrupts Bone Remodeling and Contributes to Bone Loss in Chinese Population with Skeletal Fluorosis.
| Biological Trace Element Research | Long H, Liu Y, Lei P, Hu T, Shao Z, Luo Y, Zhang S, Li J, Luo P, Zhang Z, Wei S. |
Bone Density Osteoblasts Osteoclasts Radiographic Appearance Skeletal Fluorosis Tea Urine-F Human Study

Abstract

Original abstract online at
https://link.springer.com/article/10.1007/s12011-026-05129-y

Chronic fluoride exposure from brick tea is an important yet underrecognized pathway of skeletal fluorosis in western high-altitude regions in China. However, population-based evidence explaining how internal fluoride burden translates into coordinated alterations in bone remodeling remains limited. This study aimed to clarify whether fluoride exposure affects bone loss through synchronized changes in osteoblastic and osteoclastic activity. A total of 243 adults with radiographically confirmed skeletal fluorosis were included. Brick tea consumption, urinary fluoride (UF), osteoblast- and osteoclast-related biomarkers (procollagen type I N-terminal propeptide, osteocalcin, and ?-CrossLaps), and bone mineral density were measured. Multivariable regression, confirmatory factor analysis (CFA), and structural equation modeling (SEM) were used to evaluate the relationships among exposure, internal fluoride burden, bone remodeling, and BMD. Brick tea consumption was positively associated with UF (??=?0.118 mg/L per kg/year, P < 0.001). Higher UF levels were independently associated with increased procollagen type I N-terminal propeptide (??=?6.63, P = 0.01), osteocalcin (??=?3.63, P < 0.001), and ?-CrossLaps (??=?0.07, P < 0.001), and with reduced BMD (? = -9.66, P < 0.001). CFA demonstrated that these biomarkers loaded strongly onto a single latent construct representing accelerated bone turnover (standardized loadings 0.769–0.866). SEM showed that brick tea consumption had no direct association with BMD but exerted an indirect effect through UF and bone turnover (total indirect effect = -0.044, P?=?0.045). These findings indicate that fluoride exposure from brick tea disrupts bone remodeling as a coordinated process characterized by accelerated overall bone turnover, ultimately contributing to bone loss in skeletal fluorosis.

Data Availability

The data described in the manuscript, codebook, and analytic code will be made available upon request, pending application to and approval from the corresponding author, S.W.

References

  1. Adriano DC (2001) Other trace elements. In: Adriano DC (ed) Trace elements in terrestrial environments: Biogeochemistry, bioavailability, and risks of metals. Springer, New York, NY, pp 759–796

    Chapter  Google Scholar

  2. Nielsen FH (1996) How should dietary guidance be given for mineral elements with beneficial actions or suspected of being essential? J Nutr 126:2377S-2385S. https://doi.org/10.1093/jn/126.suppl_9.2377S

  3. Meena L, Gupta R (2021) Skeletal fluorosis. N Engl J Med 385:1510–1510. https://doi.org/10.1056/NEJMicm2103503

    Article  PubMed  Google Scholar

  4. Joseph A, Rajan R, Paul J et al (2022) The continuing crippling challenge of skeletal fluorosis – Case series and review of literature. J Clin Translational Endocrinology: Case Rep 24:100114. https://doi.org/10.1016/j.jecr.2022.100114

    Article  Google Scholar

  5. World Health Organization (2019) Preventing disease through healthy environments: inadequate or excess fluoride: a major public health concern. https://www.who.int/publications/i/item/WHO-CED-PHE-EPE-19.4.5

  6. Yadav KK, Kumar S, Pham QB et al (2019) Fluoride contamination, health problems and remediation methods in Asian groundwater: A comprehensive review. Ecotoxicol Environ Saf 182:109362. https://doi.org/10.1016/j.ecoenv.2019.06.045

    Article  CAS  PubMed  Google Scholar

  7. Senevirathna L, Ratnayake HE, Jayasinghe N et al (2023) Water fluoridation in Australia: A systematic review. Environ Res 237:116915. https://doi.org/10.1016/j.envres.2023.116915

    Article  CAS  PubMed  Google Scholar

  8. Araya D, Podgorski J, Kumi M et al (2022) Fluoride contamination of groundwater resources in Ghana: Country-wide hazard modeling and estimated population at risk. Water Res 212:118083. https://doi.org/10.1016/j.watres.2022.118083

    Article  CAS  PubMed  Google Scholar

  9. Cao H, Xie X, Wang Y, Liu H (2022) Predicting geogenic groundwater fluoride contamination throughout China. J Environ Sci 115:140–148. https://doi.org/10.1016/j.jes.2021.07.005

    Article  CAS  Google Scholar

  10. Solanki YS, Agarwal M, Gupta AB et al (2022) Fluoride occurrences, health problems, detection, and remediation methods for drinking water: A comprehensive review. Sci Total Environ 807:150601. https://doi.org/10.1016/j.scitotenv.2021.150601

    Article  CAS  PubMed  Google Scholar

  11. Podgorski J, Berg M (2022) Global analysis and prediction of fluoride in groundwater. Nat Commun 13:4232. https://doi.org/10.1038/s41467-022-31940-x

    Article  CAS  PubMed  PubMed Central  Google Scholar

  12. Yang C, Wang Y, Xu H (2017) Treatment and prevention of skeletal fluorosis. Biomed Environ Sci 30:147–149. https://doi.org/10.3967/bes2017.020

    Article  CAS  PubMed  Google Scholar

  13. Sun D, Gao Y, Liu H (2019) Achievements and prospects of endemic disease prevention and control in China in past 70 years. zgggws 35:793–796. https://doi.org/10.11847/zgggws1124576

    Article  Google Scholar

  14. Srivastava S, Flora SJS (2020) Fluoride in drinking water and skeletal fluorosis: a review of the global impact. Curr Envir Health Rpt 7:140–146. https://doi.org/10.1007/s40572-020-00270-9

    Article  CAS  Google Scholar

  15. Qiang LI, Jun ZZ (2021) Prevalence of brick tea-type fluorosis in children aged 8–12 years in Qinghai Province, China. BES 34:334–336. https://doi.org/10.3967/bes2021.044

    Article  CAS  Google Scholar

  16. Gao H, Zhao Q, Zhang X et al (2014) Localization of fluoride and aluminum in subcellular fractions of tea leaves and roots. J Agric Food Chem 62:2313–2319. https://doi.org/10.1021/jf4038437

    Article  CAS  PubMed  Google Scholar

  17. Zhang R, Zhang H, Chen Q et al (2017) Composition, distribution and risk of total fluorine, extractable organofluorine and perfluorinated compounds in Chinese teas. Food Chem 219:496–502. https://doi.org/10.1016/j.foodchem.2016.09.136

    Article  CAS  PubMed  Google Scholar

  18. Chandrajith R, Bhagya S, Diyabalanage S et al (2022) Exposure assessment of fluoride intake through commercially available black tea (Camellia sinensis L.) from areas with high incidences of chronic kidney disease with undetermined origin (CKDu) in Sri Lanka. Biol Trace Elem Res 200:526–534. https://doi.org/10.1007/s12011-021-02694-2

    Article  CAS  PubMed  Google Scholar

  19. Cao J, Zhao Y, Liu J et al (2003) Brick tea fluoride as a main source of adult fluorosis. Food Chem Toxicol 41:535–542. https://doi.org/10.1016/S0278-6915(02)00285-5

    Article  CAS  PubMed  Google Scholar

  20. Cao J, Zhao Y, Liu JW (1998) Safety evaluation and fluorine concentration of pu’er brick tea and bianxiao brick tea. Food Chem Toxicol 36:1061–1063. https://doi.org/10.1016/S0278-6915(98)00087-8

    Article  CAS  PubMed  Google Scholar

  21. National Health Commission of the People’s Republic of China (2022) Diagnostic standard for endemic skeletal fluorosis. WS/T, pp 192–2021

  22. National Health Commission of the People’s Republic of China (2015) Determination of fluoride in urine – Ion selective electorde method (WS/T 89-2015)

  23. Chang R, Zhao W, Zhou B et al (2025) Environmental fluoride exposure and bone metabolism: Molecular pathways and health implications. J Environ Sci. https://doi.org/10.1016/j.jes.2025.11.010

    Article  Google Scholar

  24. Godebo TR, Jeuland M, Tekle-Haimanot R et al (2019) Bone quality in fluoride-exposed populations: A novel application of the ultrasonic method. Bone Rep 12:100235. https://doi.org/10.1016/j.bonr.2019.100235

    Article  PubMed  PubMed Central  Google Scholar

  25. Li H, Chen X, Zhang Z et al (2023) Microstructural analysis of cancellous bone in fluorosis Rats. Biol Trace Elem Res 201:4827–4833. https://doi.org/10.1007/s12011-023-03564-9

    Article  CAS  PubMed  Google Scholar

  26. Veneri F, Iamandii I, Vinceti M et al (2023) Fluoride exposure and skeletal fluorosis: a systematic review and dose-response meta-analysis. Curr Envir Health Rpt 10:417–441. https://doi.org/10.1007/s40572-023-00412-9

    Article  CAS  Google Scholar

  27. Lv Y, Kang L, Wu G (2016) Fluorosis increases the risk of postmenopausal osteoporosis by stimulating interferon ?. Biochem Biophys Res Commun 479:372–379. https://doi.org/10.1016/j.bbrc.2016.09.083

    Article  CAS  PubMed  Google Scholar

  28. Jin Y, Zhou B-H, Zhao J et al (2023) Fluoride-induced osteoporosis via interfering with the RANKL/RANK/OPG pathway in ovariectomized rats: Oophorectomy shifted skeletal fluorosis from osteosclerosis to osteoporosis. Environ Pollut 336:122407. https://doi.org/10.1016/j.envpol.2023.122407

    Article  CAS  PubMed  Google Scholar

  29. Cao J, Zhao Y, Liu J et al (2003) Brick tea fluoride as a main source of adult fluorosis. Food Chem Toxicol 41:535–542. https://doi.org/10.1016/S0278-6915(02)00285-5

    Article  CAS  PubMed  Google Scholar

  30. Rawat N, Bafana A (2024) Health risk modeling and risk factors of fluorosis in the fluoride endemic village of Maharashtra: A cross-sectional study. Environ Monit Assess 196:1230. https://doi.org/10.1007/s10661-024-13330-6

    Article  CAS  PubMed  Google Scholar

  31. Dhole S, Kamble B, Saluja R et al (2025) Association of fluoride biomarker levels with osteoarthritis severity: A cross-sectional study from a fluorosis-endemic region in India. Cureus 17:e91606. https://doi.org/10.7759/cureus.91606

    Article  PubMed  PubMed Central  Google Scholar

  32. Idowu OS, Azevedo LB, Valentine RA et al (2019) The use of urinary fluoride excretion to facilitate monitoring fluoride intake: A systematic scoping review. PLoS ONE 14:e0222260. https://doi.org/10.1371/journal.pone.0222260

    Article  CAS  PubMed  PubMed Central  Google Scholar

  33. Sauvé J-F, Lévesque M, Huard M et al (2015) Creatinine and specific gravity normalization in biological monitoring of occupational exposures. J Occup Environ Hyg 12:123–129. https://doi.org/10.1080/15459624.2014.955179

    Article  CAS  PubMed  Google Scholar

  34. Li A, Wu L, Zhang R et al (2026) Fluoride exposure disrupts creatinine homeostasis and undermines the reliability of urinary metabolomics normalization. Ecotoxicol Environ Saf 309:119555. https://doi.org/10.1016/j.ecoenv.2025.119555

    Article  CAS  PubMed  Google Scholar

  35. Appelman-Dijkstra NM, Papapoulos SE (2015) Modulating bone resorption and bone formation in opposite directions in the treatment of postmenopausal osteoporosis. Drugs 75:1049–1058. https://doi.org/10.1007/s40265-015-0417-7

    Article  CAS  PubMed  PubMed Central  Google Scholar

  36. Xiao W, Li S, Pacios S et al (2016) Bone remodeling under pathological conditions. Front Oral Biol 18:17–27. https://doi.org/10.1159/000351896

    Article  PubMed  Google Scholar

  37. Eastell R, Szulc P (2017) Use of bone turnover markers in postmenopausal osteoporosis. Lancet Diabetes Endocrinol 5:908–923. https://doi.org/10.1016/S2213-8587(17)30184-5

    Article  PubMed  Google Scholar

  38. Jiang N, Guo F, Xu W et al (2020) Effect of fluoride on osteocyte-driven osteoclastic differentiation. Toxicology 436:152429. https://doi.org/10.1016/j.tox.2020.152429

    Article  CAS  PubMed  Google Scholar

  39. Qiao L, Liu X, He Y et al (2021) Progress of signaling pathways, stress pathways and epigenetics in the pathogenesis of skeletal fluorosis. Int J Mol Sci 22:11932. https://doi.org/10.3390/ijms222111932

    Article  CAS  PubMed  PubMed Central  Google Scholar

  40. Liu X-L, Li C-C, Liu K-J et al (2012) The influence of fluoride on the expression of inhibitors of Wnt/?-Catenin signaling pathway in Rat Skin fibroblast cells. Biol Trace Elem Res 148:117–121. https://doi.org/10.1007/s12011-012-9333-9

    Article  CAS  PubMed  Google Scholar

  41. Ma L, Zhang R, Li D et al (2021) Fluoride regulates chondrocyte proliferation and autophagy via PI3K/AKT/mTOR signaling pathway. Chemico-Biol Interact 349:109659. https://doi.org/10.1016/j.cbi.2021.109659

    Article  CAS  Google Scholar

  42. Yu Y, Yang D, Zhu H et al (2012) [Expression of mRNA and protein of p38, Osx, PI3K and Akt1 in rat bone with chronic fluorosis]. Zhonghua Bing Li Xue Za Zhi 41:622–626. https://doi.org/10.3760/cma.j.issn.0529-5807.2012.09.011

    Article  CAS  PubMed  Google Scholar

  43. Wang Z, Yang X, Yang S et al (2011) Sodium fluoride suppress proliferation and induce apoptosis through decreased insulin-like growth factor-I expression and oxidative stress in primary cultured mouse osteoblasts. Arch Toxicol 85:1407–1417. https://doi.org/10.1007/s00204-011-0697-y

    Article  CAS  PubMed  Google Scholar

  44. Wang Q, Cai J, Fan J et al (2023) Effect of Nrf2/ARE signaling pathways on oxidative damage induced by sodium fluoride in rat osteoblasts. Mater Express 13:1241–1248. https://doi.org/10.1166/mex.2023.2451

    Article  CAS  Google Scholar

  45. Wen C, Zhang Q, Xie F, Jiang J (2022) Brick tea consumption and its relationship with fluorosis in Tibetan areas. Front Nutr 9. https://doi.org/10.3389/fnut.2022.1030344

  46. Jin C, Yan Z, Jianwei L (2001) Processing procedures of brick tea and their influence on fluorine content. Food Chem Toxicol 39:959–962. https://doi.org/10.1016/S0278-6915(01)00039-4

    Article  CAS  PubMed  Google Scholar

  47. National Health Commission of the People’s Republic of China (2005) Fluoride content of brick tea. GB/19965?–?2005

  48. Hao Hao Y, Xiaojing P, Wen et al (2024) Analysis of fluoride content in brick tea from tea-drinking endemic fluorosis areas in Sichuan Province in 2022. J Prev Med Inform 40:1558–1564. https://doi.org/10.19971/j.cnki.1006-4028.240679

    Article  Google Scholar

Download references

Acknowledgements

We sincerely thank all participants of the China Fluorosis Cohort (CFC) for their valuable contributions to this study. We also thank the local Centers for Disease Control and Prevention (CDC) teams in Sichuan, as well as the participating doctors and community workers, for their assistance during field investigation and data collection.

Funding

This work was supported by the National Key Research and Development Program of China (Grant No. 2022YFC2503003) and the Guizhou Provincial Major Scientific and Technological Program (2024-015).

Author information

Author notes

  1. Hongjiang Long and Yubo Liu contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, 561113, China

    Hongjiang Long, Yubo Liu, Pinggui Lei, Ting Hu, Zhijuan Shao, Yu Luo, Shuling Zhang, Peng Luo, Zhenting Zhang & Shaofeng Wei

  2. Forensic medical expertise center, Forensic academy, Guizhou Medical University, Guiyang, 550004, China

    Yubo Liu

  3. Department of Radiology, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China

    Pinggui Lei

  4. Sichuan Provincial Center for Disease Control and Prevention, Chengdu, 610044, China

    Jinshu Li

  5. Guizhou Institute of Industrial Development, Guiyang, 550081, China

    Peng Luo

Contributions

All authors contributed to the study conception and design. H.L. wrote the main manuscript text and performed data analysis with model fitting. Y.L., T.H., and J.L. conducted data pre-processing and verification. Z.S., Y.L., and S.Z. performed field investigations and data collection. Z.Z., P.L. and S.W supervised the study and revised the manuscript. All authors reviewed and approved the final manuscript.

Corresponding authors

Correspondence to Zhenting Zhang or Shaofeng Wei.

Ethics declarations

Ethics Approval

The study protocol complied with the principles of the Declaration of Helsinki (1964) and relevant ethical guidelines and was approved by the Ethical Committee of Guizhou Medical University (approval number: 2023???189).

Consent to Participate

Written informed consent was obtained from all participants included in the study.

Consent to Publish

is not applicable.

Competing Interests

The authors declare no competing interests.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary Material 1 (download DOCX )