Skip to main content

Advertisement

SpringerLink
Log in

Effects of Fluoride and Cadmium co-Exposure on Bone in Male Rats

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Although cadmium (Cd) and fluoride may both have adverse effects on bone, most studies focus on a single agent. In this study, we investigated the effects of cadmium and fluoride on bone at a relative low level. Sprague–Dawley male rats were assigned randomly into four groups which were given sodium chloride, cadmium (50mg/L), and fluoride (20mg/L) alone, or in combination via drinking water. At the 12th week, urine, blood, and bone tissues were collected for biomarker assay, biomechanical assay, and histological assay. Cadmium had significantly adverse effects on bone mineral density, bone biomechanical property, and bone microstructure. Fluoride slightly increased vertebral bone mineral density but negatively affected bone biomechanical property and bone microstructure. Fluoride could reverse the decrease of vertebral bone mineral density caused by cadmium but could not improve the damage of bone biomechanical property and microstructure caused by cadmium. Tartrate-resistant acid phosphatase 5b levels in rats treated with cadmium and fluoride or in combination were 1–2.5 folds higher than the control. Our data suggest that low level of fluoride could reverse the decrease of vertebral bone mineral density caused by cadmium exposure but has no influence on appendicular skeleton damage caused by cadmium.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Wu X, Liang Y, Jin T, Ye T, Kong Q, Wang Z, Lei L, Bergdahl IA, Nordberg GF (2008) Renal effects evolution in a Chinese population after reduction of cadmium exposure in rice. Environ Res 108:233–238

    Article  PubMed  CAS  Google Scholar 

  2. Nordberg GF (1996) Current issues in low-dose cadmium toxicology: nephrotoxicity and carcinogenicity. Environ Sci 4:133–147

    CAS  Google Scholar 

  3. Bernard A (2008) Cadmium & its adverse effects on human health. Indian J Med Res 128:557–564

    PubMed  CAS  Google Scholar 

  4. Staessen JA, Roels HA, Emelianov D, Kuznetsova T, Thijs L, Vangronsveld J, Fagard R (1999) Environment exposure to cadmium, forearm bone density, and risk of fractures: prospective population study. Lancet 353:1140–1144

    Article  PubMed  CAS  Google Scholar 

  5. Alfvén T, Elinder CG, Carlsson MD, Grubb A, Hellström L, Persson B, Pettersson C, Spång G, Schütz A, Järup L (2000) Low-level cadmium exposure and osteoporosis. J Bone Miner Res 15(8):1579–1586

    Article  PubMed  Google Scholar 

  6. Wang H, Zhu G, Shi Y, Weng S, Jin T, Kong Q, Nordberg GF (2003) Influence of environmental cadmium exposure on forearm bone density. J Bone Miner Res 18:553–560

    Article  PubMed  CAS  Google Scholar 

  7. Åkesson A, Bjellerup P, Lundh T, Lidfeldt J, Nerbrand C, Samsioe G, Skerfving S, Vahter M (2006) Cadmium-induced effects on bone in a population-based study of women. Environ Health Perspect 114:830–834

    Article  PubMed  Google Scholar 

  8. Wilson AK, Cerny EA, Smith BD, Wagh A, Bhattacharyya MH (2009) Effects of cadmium on osteoclast formation and activity in vitro. Toxicol Appl Pharmacol 140(2):451–460

    Article  Google Scholar 

  9. Chen X, Zhu G, Gu S, Jin T, Shao C (2009) Effects of cadmium on osteoblasts and osteoclasts in vitro. Environ Toxicol Pharmacol 28:232–236

    Article  PubMed  CAS  Google Scholar 

  10. Chen X, Zhu G, Jin T, Zhou Z, Gu S, Qiu J, Xiao H (2012) Cadmium stimulates RAW264.7 cells differentiation into osteoclasts in the presence of osteoblast. Biol Trace Elem Res 146:349–353

    Article  PubMed  CAS  Google Scholar 

  11. Ayoob S, Gupta AK (2006) Fluoride in drinking water: a review on the status and stress effects. Crit Rev Environ Sci Technol 36:433–487

    Article  CAS  Google Scholar 

  12. Sícha VV (1990) Prevention of tooth decay with fluoride. Cesk Pediatr 45(1):42–43

    PubMed  Google Scholar 

  13. Farley SM, Libanati CR, Mariano-Menez MR, Tudtud-Hans LA, Schulz EE, Baylink DJ (1990) Fluoride therapy for osteoporosis promotes a progressive increase in spinal bone density. J Bone Miner Res 5(Suppl 1):S37–S42

    PubMed  Google Scholar 

  14. Farley SM, Wergedal JE, Farley JR, Javier GN, Schulz EE, Talbot JR, Libanati CR, Lindegren L, Bock M, Goette MM (1992) Spinal fractures during fluoride therapy for osteoporosis: relationship to spinal bone density. Osteoporos Int 2:213–218

    Article  PubMed  CAS  Google Scholar 

  15. Pak CYC, Sakhaee K, Adams-Huet B, Peterson RD, Breslau NA, Boyd P, Poindexter JR, Herzog J, Heard-Sakhaee A, Haynes S, Adams-Huet B, Reisch JS (1994) Slow-release sodium fluoride in the management of postmenopausal osteoporosis. Ann Intern Med 120:625–632

    Article  PubMed  CAS  Google Scholar 

  16. Kleerekoper M, Mendlovic DB (1993) Sodium fluoride therapy of postmenopausal osteoporosis. Endocr Rev 14(3):312–323

    PubMed  CAS  Google Scholar 

  17. Heaney RP (1994) Fluoride and osteoporosis. Ann Intern Med 120(8):689–690

    Article  PubMed  CAS  Google Scholar 

  18. Riggs BL, Hodgson SF, O’Fallon WM, Chao EY, Wahner HW, Muhs JM, Cedel SL, Melton LJ 3rd (1990) Influence of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis. N Engl J Med 322:802–809

    Article  PubMed  CAS  Google Scholar 

  19. Carter DR, Beaupré GS (1990) Effects of fluoride treatment on bone strength. J Bone Miner Res 5:S177–S184

    Article  PubMed  CAS  Google Scholar 

  20. Sogaard CH, Mosekilde L, Schwartz W, Leidig G, Minne HW, Ziegler R (1995) Effects of fluoride on rat vertebral body biomechanical competence and bone mass. Bone 16:163–169

    PubMed  CAS  Google Scholar 

  21. Rizzoli R, Chevalley T, Slosman DO, Bonjour JP (1995) Sodium monofluorophosphate increases vertebral bone mineral density in patients with corticosteroid-induced osteoporosis. Osteoporos Int 5:39–46

    Article  PubMed  CAS  Google Scholar 

  22. Lindskog S, Flores ME, Lilja E, Hammarström L (1989) Effect of a high dose of fluoride on resorbing osteoclasts in vivo. Scand J Dent Res 97:483–487

    PubMed  CAS  Google Scholar 

  23. Qu WJ, Zhong DB, Wu PF, Wang JF, Han B (2008) Sodium fluoride modulates caprine osteoblast proliferation and differentiation. J Bone Miner Metab 26:328–334

    Article  PubMed  CAS  Google Scholar 

  24. National Research Council (NRC) (2006) Fluoride in drinking water. A scientific review of EPA’s standards. National Academy Press, Washington, DC

    Google Scholar 

  25. Chen X, Zhu G, Jin T, Gu S, Tan M, Xiao H, Qiu J (2011) Cadmium exposure induced itai-itai-like syndrome in male rats. Cent Eur J Med 6:425–434

    Article  CAS  Google Scholar 

  26. Husdan H, Rapoport A (1968) Estimation of creatinine by the Jaffe reaction. A comparison of three methods. Clin Chem 14:222–238

    PubMed  CAS  Google Scholar 

  27. Chen X, Zhu G, Jin T, Gu S (2009) Effects of cadmium on forearm bone density after reduction of cadmium exposure for 10 years in a Chinese population. Environ Int 35:1164–1168

    Article  PubMed  CAS  Google Scholar 

  28. Jiang Y, Zhao J, Van Audekercke R, Dequeker J, Geusens P (2000) Effects of low-dose long-term sodium fluoride preventive treatment on rat bone mass and biomechanical properties. Toxicology 146:161–169

    Article  Google Scholar 

  29. Sprando RL, Collins TF, Black TN, Rorie J, Ames MJ, O’Donnell M (1996) Testing the potential of sodium fluoride to affect spermatogenesis in the rat. Calcif Tissue Int 58:30–39

    Article  Google Scholar 

  30. Wang YN, Xiao KQ, Liu JL, Dallner G, Guan ZZ (1997) Effect of long-term fluoride exposure on lipid composition in rat liver. Food Chem Toxicol 35:881–890

    Article  Google Scholar 

  31. Xiong X, Liu J, He W, Xia T, He P, Chen X, Yang K, Wang A (2007) Dose–effect relationship between drinking water fluoride levels and damage to liver and kidney functions in children. Environ Res 103:112–116

    Article  PubMed  CAS  Google Scholar 

  32. Smith FA, Gardner DE, Hodge HC (1950) Investigations on the metabolism of fluoride. II. Fluoride content of blood and urine as a function of the fluorine in drinking water. J Dent Res 29:596–600

    Article  PubMed  CAS  Google Scholar 

  33. Spencer H, Lewin I, Fowler J, Samachson J (1969) Effect of sodium fluoride on calcium absorption and balances in man. Am J Clin Nutr 22:381–390

    PubMed  CAS  Google Scholar 

  34. Sarić MM, Blanusa M, Piasek M, Varnai VM, Juresa D, Kostial K (2002) Effect of dietary calcium on cadmium absorption and retention in suckling rats. Biometals 15:175–182

    Article  PubMed  Google Scholar 

  35. Brzóska MM, Moniuszko-Jakoniuk J (2004) Low-level lifetime exposure to cadmium decreases skeletal mineralization and enhances bone loss in aged rats. Bone 35:1180–1191

    Article  PubMed  Google Scholar 

  36. Brzóska MM, Moniuszko-Jakoniuk J (2005) Bone metabolism of male rats chronically exposed to Cd. Toxicol Appl Pharmacol 207:195–211

    Article  PubMed  Google Scholar 

  37. Brzóska MM, Moniuszko-Jakoniuk J (2005) Effects of chronic exposure to cadmium on the mineral status and mechanical properties of lumbar spine of male rats. Toxicol Lett 157:161–172

    Article  PubMed  Google Scholar 

  38. Chavassieux P, Boivin G, Serre CM, Meunier PJ (1993) Fluoride increases rat osteoblast function and population after in vivo administration but not after in vitro exposure. Bone 14:721–725

    Article  PubMed  CAS  Google Scholar 

  39. Turner CH, Hasegawa K, Zhang W, Wilson M, Li Y, Dunipace AJ (1995) Fluoride reduces bone strength in older rats. J Dent Res 74:1475–1481

    Article  PubMed  CAS  Google Scholar 

  40. Aaseth J, Shimshi M, Gabrilove JL, Birketvedt GS (2004) Fluoride: a toxic or therapeutic agent in the treatment of osteoporosis? J Trace Elem Exp Med 17:83–92

    Article  CAS  Google Scholar 

  41. Parisien M, Mellish RW, Silverberg SJ, Shane E, Lindsay R, Bilezikian JP, Dempster DW (1992) Maintenance of cancellous bone connectivity in hyperparathyroidism: trabecular strut analysis. J Bone Miner Res 7:913–919

    Article  PubMed  CAS  Google Scholar 

  42. Halleen JM, Tiitinen SL, Ylipahkala H, Fagerlund KM, Väänänen HK (2006) Tartrate-resistant acid phosphatase 5b (TRACP 5b) as a marker of bone resorption. Clin Lab 52:499–509

    PubMed  CAS  Google Scholar 

  43. Halleen JM, Alatalo SL, Janckila AJ (2001) Serum tartrate-resistant acid phosphatase is a specific and sensitive marker of bone resorption. Clin Chem 47:597–600

    PubMed  CAS  Google Scholar 

  44. Alatalo SL, Peng Z, Janckila AJ, Kaija H, Vihko P, Vaananen HK, Halleen JM (2003) A novel immunoassay for the determination of tartrate-resistant acid phosphatase 5b from rat serum. J Bone Miner Res 18:134–139

    Article  PubMed  CAS  Google Scholar 

  45. Halleen JM, Alatalo SL, Suominen H, Cheng S, Janckila AJ, Väänänen HK (2000) Tartrate-resistant acid phosphatase 5b: a novel serum marker of bone resorption. J Bone Miner Res 15:1337–1345

    Article  PubMed  CAS  Google Scholar 

  46. Yu J, Gao Y, Sun D (2013) Effect of fluoride and low versus high levels of dietary calcium on mRNA expression of osteoprotegerin and osteoprotegerin ligand in the bone of rats. Biol Trace Elem Res 153:387–395

    Article  Google Scholar 

  47. Pei J, Li B, Gao Y, Wei Y, Zhou L, Yao H, Wang J, Sun D (2012) Fluoride decreased osteoclastic bone resorption through the inhibition of NFATc1 gene expression. Environ Toxicol. doi:10.1002/tox.21784

    PubMed  Google Scholar 

  48. Turner CH, Garetto LP, Dunipace AJ, Zhang W, Wilson ME, Grynpas MD, Chachra D, McClintock R, Peacock M, Stookey GK (1997) Fluoride treatment increased serum IGF-1, bone turnover, and bone mass, but not bone strength, in rabbits. Calcif Tissue Int 61:77–83

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was funded by the National Natural Science Foundation of China (no. 81102148, 81271630), Shanghai Health Bureau (2012198), and Shanghai Municipal Science and Technology Commission (41902502).

Conflict of Interest

The authors declare that there is no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Radiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China

    Xiao Chen & Zhongqiu Wang

  2. Shanghai Public Health Clinical Center, Shanghai, China

    Boyin Qin & Wenjiang Zhou

  3. Institute of Radiation Medicine, Fudan University, Shanghai, China

    Xufang Li & Guoying Zhu

  4. Department of Occupational Medicine, School of Public Health, Fudan University, Shanghai, China

    Taiyi Jin

Authors
  1. Xiao Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Boyin Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xufang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Taiyi Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Guoying Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wenjiang Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhongqiu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Wenjiang Zhou or Zhongqiu Wang.

Additional information

Xiao Chen and Boyin Qin contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, X., Qin, B., Li, X. et al. Effects of Fluoride and Cadmium co-Exposure on Bone in Male Rats. Biol Trace Elem Res 154, 396–402 (2013). https://doi.org/10.1007/s12011-013-9750-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-013-9750-4

Keywords

Search

Navigation