Skip to main content

Advertisement

SpringerLink
Log in

Bone Strength in Growing Rats Treated with Fluoride: a Multi-dose Histomorphometric, Biomechanical and Densitometric Study

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

Abstract

Bone deformation and fragility are common signs of skeletal fluorosis. Disorganisation of bone tissue and presence of inflammatory foci were observed after fluoride (F−) administration. Most information about F− effects on bone has been obtained in adult individuals. However, in fluorosis areas, children are a population very exposed to F− and prone to develop not only dental but also skeletal fluoroses. The aim of this work was to evaluate the bone parameters responsible for the effect of different doses of F− on fracture load of the trabecular and cortical bones using multivariate analysis in growing rats. Twenty-four 21-day-old Sprague-Dawley rats were divided into four groups: F0, F20, F40 and F80, which received orally 0, 20, 40 or 80 μmol F−/100 g bw/day, respectively, for 30 days. After treatment, tibiae were used for measuring bone histomorphometric and connectivity parameters, bone mineral density (BMD) and bone cortical parameters. The femurs were used for biomechanical tests and bone F− content. Trabecular bone volume was significantly decreased by F−. Consistently, we observed a significant decrease in fracture load and Young’s modulus (YM) of the trabecular bone in F−-treated groups. However, cortical bone parameters were not significantly affected by F−. Moreover, there were no significant differences in cortical nor trabecular BMD. Multivariate analysis revealed a significant correlation between the trabecular fracture load and YM but not with bone volume or BMD. It is concluded that when F− is administered as a single daily dose, it produces significant decrease in trabecular bone strength by changing the elasticity of the trabecular bone.

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

Similar content being viewed by others

References

  1. World Health Organization (1970) Fluoride and human health. World Health Organization, Geneva

    Google Scholar 

  2. Cook HA (1969) Fluoride and tea. Lancet 2:329

    Article  PubMed  CAS  Google Scholar 

  3. Kramer L, Osis D, Wiatrowski E, Spencer H (1974) Dietary fluoride in different areas in the United States. Am J Clin Nutr 27(6):590–594

    Article  PubMed  CAS  Google Scholar 

  4. Fina BL, Lupo M, Dri N, Lombarte M, Rigalli A (2016) Comparison of fluoride effects on germination and growth of Zea mays, Glycine max and Sorghum vulgare. J Sci Food Agric 96(11):3679–3687. https://doi.org/10.1002/jsfa.7551

    Article  PubMed  CAS  Google Scholar 

  5. Caverzasio J, Palmer G, Bonjour JP (1998) Fluoride: mode of action. Bone 22:585–589

    Article  PubMed  CAS  Google Scholar 

  6. Gazzano E, Bergandi L, Riganti C, Aldieri E, Doublier S, Costamagna C, Bosia A, Ghigo D (2010) Fluoride effects: the two faces of Janus. Curr Med Chem 17(22):2431–2441. https://doi.org/10.2174/092986710791698503

    Article  PubMed  CAS  Google Scholar 

  7. Opydo-Szymaczek J, Gerreth K (2015) Developmental enamel defects of the permanent first molars and incisors and their association with dental caries in the region of Wielkopolska, Western Poland. Oral Health Prev Dent 13:461–469. https://doi.org/10.3290/j.ohpd.a33088

    Article  PubMed  Google Scholar 

  8. Everett ET (2011) Fluoride’s effects on the formation of teeth and bones, and the influence of genetics. J Dent Res 90(5):552–560. https://doi.org/10.1177/0022034510384626

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Moudgil A, Srivastava RN, Vasudev A, Bagga A, Gupta A (1986) Fluorosis with crippling skeletal deformities. Indian Pediatr 23(10):767–773

    PubMed  CAS  Google Scholar 

  10. Posner AS, Eanes ED, Harper RA, Zipkin I (1963) X-ray diffraction analysis of the effect of fluoride on human bone apatite. Arch Oral Biol 8(4):549–570. https://doi.org/10.1016/0003-9969(63)90071-2

    Article  PubMed  CAS  Google Scholar 

  11. Grynpas MD (1990) Fluoride effects on bone crystals. J Bone Miner Res 5(S1):S169–S175. https://doi.org/10.1002/jbmr.5650051362

    Article  PubMed  CAS  Google Scholar 

  12. Mousny M, Omelon S, Wise L, Everett ET, Dumitriu M, Holmyard DP, Banse X, Devogelaer JP, Grynpas MD (2008) Fluoride effects on bone formation and mineralization are influence by genetics. Bone 43(6):1067–1074. https://doi.org/10.1016/j.bone.2008.07.248

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Farr JN, Khosla S (2015) Skeletal changes through the lifespan-from growth to senescence. Nat Rev Endocrinol 11:513–521. https://doi.org/10.1038/nrendo.2015.89

    Article  PubMed  PubMed Central  Google Scholar 

  14. Golden NH, Abrams SA (2014) Optimizing bone health in children and adolescents. Pediatrics 134(4):e1229–e1243. https://doi.org/10.1542/peds.2014-2173

    Article  PubMed  Google Scholar 

  15. Teotia M, Teotia SP, Singh KP (1998) Endemic chronic fluoride toxicity and dietary calcium deficiency interaction syndromes of metabolic bone disease and deformities in India: year 2000. Indian J Pediatr 65(3):371–381. https://doi.org/10.1007/BF02761130

    Article  PubMed  CAS  Google Scholar 

  16. Vilasrao GS, Kamble KM, Sabat RN (2014) Child fluorosis in Chhattisgarh, India: a community-based survey. Indian Pediatr 51(11):903–905. https://doi.org/10.1007/s13312-014-0525-6

    Article  PubMed  Google Scholar 

  17. De Almeida BS, Da Silva Cardoso VE, Buzalaf MAR (2007) Fluoride ingestion from toothpaste and diet in 1- to 3-year-old Brazilian children. Community Dent Oral Epidemiol 35(1):53–63. https://doi.org/10.1111/j.1600-0528.2007.00328.x

    Article  PubMed  Google Scholar 

  18. García-Camba de la Muela JM, García-hoyos F, Varela Morales M, González Sanz A (2009) Demonstration of fluoride systemic absorption secondary to toothbrusing with fluoride dentifrice in children. Rev Esp Salud Publica 83(3):415–425. https://doi.org/10.1590/S1135-57272009000300007

    Article  PubMed  Google Scholar 

  19. Guo XE (2008) What is nanomechanics of bone and why is it important? J Musculoskelet Neuronal Interact 8(7301):327–328. https://doi.org/10.1136/bmj.322.7301.1536

    Article  PubMed  CAS  Google Scholar 

  20. Willems HME, van den Heuvel EGHM, Castelein S, Buisman JK, Bronckers ALJJ, Bakker AD, Klein-Nulend J (2011) Fluoride inhibits the response of bone cells to mechanical loading. Odontology 99(2):112–118. https://doi.org/10.1007/s10266-011-0013-6

    Article  PubMed  CAS  Google Scholar 

  21. Stein ID, Granik G (1980) Human vertebral bone: relation of strength, porosity, and mineralization to fluoride content. Calcif Tissue Int 32(1):189–194. https://doi.org/10.1007/BF02408540

    Article  PubMed  CAS  Google Scholar 

  22. Brun LR, Roma SM, Pérez F, Rigalli A (2012) Inflamación en el tejido óseo de ratas inducida por fluoruro de sodio. Actual Osteol 8:19–28

    Google Scholar 

  23. Fina BL, Lombarte M, Rigalli JP, Rigalli A (2014) Fluoride increases superoxide production and impairs the respiratory chain in ROS 17/2.8 osteoblastic cells. PLoS One 9(6):e100768. https://doi.org/10.1371/journal.pone.0100768

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Harriss DJ, Atkinson G (2011) Update—ethical standards in sport and exercise science research. Int J Sports Med 32(10):819–821. https://doi.org/10.1055/s-0029-1237378

    Article  PubMed  CAS  Google Scholar 

  25. Olfert ED, Cross BM, McWilliam A (1993) Guide to the care and use of experimental animals. Canadian C, Ottawa

    Google Scholar 

  26. Beinlich AD, Brun LRM, Rigalli A, Puche RC (2003) Intestinal absorption of disodium monofluorophosphate in the rat as affected by concurrent administration of calcium. Arzneimittel-forsch Drug Res 53(08):584–589. https://doi.org/10.1055/s-0031-1297153

    Article  CAS  Google Scholar 

  27. Li W, Jiang B, Cao X, Xie Y, Huang T (2017) Protective effect of lycopene on fluoride-induced ameloblasts apoptosis and dental fluorosis through oxidative stress-mediated Caspase pathways. Chem Biol Interact 261:27–34. https://doi.org/10.1016/j.cbi.2016.11.021

    Article  PubMed  CAS  Google Scholar 

  28. Pulungan ZSA, Sofro ZM, Partadiredja G (2016) Sodium fluoride does not affect the working memory and number of pyramidal cells in rat medial prefrontal cortex. Anat Sci Int. https://doi.org/10.1007/s12565-016-0384-4

  29. Dempster DW, Compston JE, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR, Parfitt AM (2013) Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 28(1):2–17. https://doi.org/10.1002/jbmr.1805

    Article  PubMed  PubMed Central  Google Scholar 

  30. Harrar K, Hamami L (2013) An interconnectivity index for osteoporosis assessment using X-ray images. J Med Biol Eng 33(6):569–575. https://doi.org/10.5405/jmbe.1294

    Article  Google Scholar 

  31. Brun LR, Brance ML, Lombarte M, Maher MC, di Loreto VE, Rigalli A (2015) Effects of yerba mate (IIex paraguariensis) on histomorphometry, biomechanics, and densitometry on bones in the rat. Calcif Tissue Int 97(5):527–534. https://doi.org/10.1007/s00223-015-0043-0

    Article  PubMed  CAS  Google Scholar 

  32. Brun LR, Pera LI, Rigalli A (2010) Bone morphometry and differences in bone fluorine containing compounds in rats treated with NaF and MFP. Biomed Pharmacother 64(1):1–6. https://doi.org/10.1016/j.biopha.2008.10.009

    Article  PubMed  CAS  Google Scholar 

  33. Moreno H, Lombarte M, Di Loreto VE (2009) Bones and bone tissue. In: Rigalli A, Di Loreto VE (eds) Experimental surgical models in the laboratory rat. CRC Press, Taylor & Francis Group, Boca Raton, pp 229–232. https://doi.org/10.1201/9781420093278.ch43

    Chapter  Google Scholar 

  34. Hoggarth CR, Bennett R, Daley-Yates PT (1991) The pharmacokinetics and distribution of pamidronate for a range of doses in the mouse. Calcif Tissue Int 49(6):416–420. https://doi.org/10.1007/BF02555853

    Article  PubMed  CAS  Google Scholar 

  35. Hogan HA, Ruhmann SP, Sampson HW (2000) The mechanical properties of cancellous bone in the proximal tibia of ovariectomized rats. J Bone Miner Res 15(2):284–292. https://doi.org/10.1359/jbmr.2000.15.2.284

    Article  PubMed  CAS  Google Scholar 

  36. Rigalli A, Alloatti R, Puche RC (1999) Measurement of total and diffusible serum fluoride. J Clin Lab Anal 13(4):151–157. https://doi.org/10.1002/(SICI)1098-2825

    Article  PubMed  CAS  Google Scholar 

  37. Development Core Team R (2011) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna

    Google Scholar 

  38. Vestergaard P, Jorgensen NR, Schwarz P, Mosekilde L (2008) Effects of treatment with fluoride on bone mineral density and fracture risk—a meta-analysis. Osteoporos Int 19(3):257–268. https://doi.org/10.1007/s00198-007-0437-6

    Article  PubMed  CAS  Google Scholar 

  39. Lombarte M, Brun LR, Brance ML et al (2014) Efecto diferencial del ácido zoledrónico sobre el hueso trabecular y cortical de ratas ovariectomizadas. Actual Osteol 10:238–246

    Google Scholar 

  40. Kaseva ME (2006) Contribution of trona (magadi) into excessive fluorosis—a case study in Maji ya Chai ward, northern Tanzania. Sci Total Environ 366(1):92–100. https://doi.org/10.1016/j.scitotenv.2005.08.049

    Article  PubMed  CAS  Google Scholar 

  41. Zhang L, Huang D, Yang J, Wei X, Qin J, Ou S, Zhang Z, Zou Y (2017) Probabilistic risk assessment of Chinese residents’ exposure to fluoride in improved drinking water in endemic fluorosis areas. Environ Pollut 222:118–125. https://doi.org/10.1016/j.envpol.2016.12.074

    Article  PubMed  CAS  Google Scholar 

  42. Paoloni JD, Fiorentino CE, Sequeira ME (2003) Fluoride contamination of aquifers in the southeast subhumid pampa, Argentina. Environ Toxicol 18(5):317–320. https://doi.org/10.1002/tox.10131

    Article  PubMed  CAS  Google Scholar 

  43. de la Sota M, Puche R, Rigalli A, Fernández LM, Benassati S, Boland R (1997) Changes in bone mass and in glucose homeostasis in subjects with high spontaneous fluoride intake. Medicina (B Aires) 57(4):417–420

    Google Scholar 

  44. Lupo M, Fina BL, Aguirre MC, Armendariz M, Rigalli A (2012) Determination of water fluoride concentration and the influence of the geographic coordinate system and time. Water Air Soil Pollut 223(8):5221–5225. https://doi.org/10.1007/s11270-012-1273-7

    Article  CAS  Google Scholar 

  45. Blanes PS, Buchhamer EE, Giménez MC (2011) Natural contamination with arsenic and other trace elements in groundwater of the Central-West region of Chaco, Argentina. J Environ Sci Health A Tox Hazard Subst Environ Eng 46(11):1197–1206. https://doi.org/10.1080/10934529.2011.598774

    Article  PubMed  CAS  Google Scholar 

  46. Seeman E (2008) Bone quality: the material and structural basis of bone strength. J Bone Miner Metab 26(1):1–8. https://doi.org/10.1007/s00774-007-0793-5

    Article  PubMed  Google Scholar 

  47. Rigalli A, Alloatti R, Menoyo I, Puche RC (1995) Comparative study of the effect of sodium fluoride and sodium monofluorophosphate on glucose homeostasis in the rat. Arzneimittelforschung 45(3):289–292

    PubMed  CAS  Google Scholar 

  48. Rigalli A, Ballina JC, Puche RC (1992) Bone mass increase and glucose tolerance in rats chronically treated with sodium fluoride. Bone Miner 16(2):101–108. https://doi.org/10.1016/0169-6009(92)90880-M

    Article  PubMed  CAS  Google Scholar 

  49. Lou D-D, Guan Z-Z, Liu Y-J, Liu YF, Zhang KL, Pan JG, Pei JJ (2013) The influence of chronic fluorosis on mitochondrial dynamics morphology and distribution in cortical neurons of the rat brain. Arch Toxicol 87(3):449–457. https://doi.org/10.1007/s00204-012-0942-z

    Article  PubMed  CAS  Google Scholar 

  50. Lupo M, Afonso M, Buzalaf R, Rigalli A (2011) Effect of fluoridated water on plasma insulin levels and glucose homeostasis in rats with renal deficiency. Biol Trace Elem Res 140(2):198–207. https://doi.org/10.1007/s12011-010-8690-5

    Article  PubMed  CAS  Google Scholar 

  51. de Carvalho JG, de Oliveira RC, Buzalaf MAR (2006) Plasma as an indicator of bone fluoride levels in rats chronically exposed to fluoride. J Appl Oral Sci 14(4):238–241. https://doi.org/10.1590/S1678-77572006000400005

    Article  PubMed  PubMed Central  Google Scholar 

  52. Lobo JGVM, Leite AL, Pereira HABS, Fernandes MS, Peres-Buzalaf C, Sumida DH, Rigalli A, Buzalaf MAR (2015) Low-level fluoride exposure increases insulin sensitivity in experimental diabetes. J Dent Res 94(7):990–997. https://doi.org/10.1177/0022034515581186

    Article  PubMed  CAS  Google Scholar 

  53. Everett ET, McHenry MAK, Reynolds N, Eggertsson H, Sullivan J, Kantmann C, Martinez-Mier EA, Warrick JM, Stookey GK (2002) Dental fluorosis: variability among different inbred mouse strains. J Dent Res 81(11):794–798. https://doi.org/10.1177/0810794

    Article  PubMed  CAS  Google Scholar 

  54. Alliston T (2014) Biological regulation of bone quality. Curr Osteoporos Rep 12(3):366–375. https://doi.org/10.1007/s11914-014-0213-4

    Article  PubMed  PubMed Central  Google Scholar 

  55. Schnitzler CM, Wing JR, Mesquita JM et al (1990) Risk factors for the development of stress fractures during fluoride therapy for osteoporosis. J Bone Miner Res 5(S1):S195–S200. https://doi.org/10.1002/jbmr.5650051330

    Article  PubMed  Google Scholar 

  56. Orcel P, De Vernejoul MC, Prier A et al (1990) Stress fractures of the lower limbs in osteoporotic patients treated with fluoride. J Bone Miner Res 5(S1):S191–S194. https://doi.org/10.1002/jbmr.5650051392

    Article  PubMed  Google Scholar 

  57. Schnitzler CM, Wing JR, Gear KA, Robson HJ (1990) Bone fragility of the peripheral skeleton during fluoride therapy for osteoporosis. Clin Orthop Relat Res 261:268–275

    Google Scholar 

  58. de Cássia Alves Nunes R, Chiba FY, Pereira AG et al (2016) Effect of sodium fluoride on bone biomechanical and histomorphometric parameters and on insulin signaling and insulin sensitivity in ovariectomized rats. Biol Trace Elem Res 173(1):144–153. https://doi.org/10.1007/s12011-016-0642-2

    Article  PubMed  CAS  Google Scholar 

  59. Franke J, Runge H, Grau P, Fengler F, Wanka C, Rempel H (1976) Physical properties of fluorosis bone. Acta Orthop Scand 47(1):20–27. https://doi.org/10.3109/17453677608998967

    Article  PubMed  CAS  Google Scholar 

  60. Ghanizadeh G, Babaei M, Naghii MR, Mofid M, Torkaman G, Hedayati M (2014) The effect of supplementation of calcium, vitamin D, boron, and increased fluoride intake on bone mechanical properties and metabolic hormones in rat. Toxicol Ind Health 30(3):211–217. https://doi.org/10.1177/0748233712452775

    Article  PubMed  CAS  Google Scholar 

  61. Nakahara H (1995) The effect of sodium fluoride on bone mineral density and bone strength in ovariectomized rats. Nihon Seikeigeka Gakkai Zasshi 69(11):1182–1192

    PubMed  CAS  Google Scholar 

  62. Sreenivasan D, Watson M, Callon K, Dray M, Das R, Grey A, Cornish J, Fernandez J (2013) Integrating micro CT indices, CT imaging and computational modelling to assess the mechanical performance of fluoride treated bone. Med Eng Phys 35(12):1793–1800. https://doi.org/10.1016/j.medengphy.2013.07.013

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Hilda Moreno for technical assistance.

Funding

This study was funded by a grant from Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) (PIP 112-200801-00341). CONICET had no role in the design, analysis or writing of this article.

Author information

Authors and Affiliations

  1. Bone Biology Laboratory, School of Medicine, Rosario National University, Rosario, S2002KTR, Santa Fe, Argentina

    Brenda Lorena Fina, Maela Lupo, Eugenia Rocío Da Ros, Mercedes Lombarte & Alfredo Rigalli

  2. National Council of Scientific and Technical Research (CONICET), Buenos Aires, Argentina

    Brenda Lorena Fina, Maela Lupo, Mercedes Lombarte & Alfredo Rigalli

  3. Rosario National University Research Council, Rosario, Argentina

    Maela Lupo, Mercedes Lombarte & Alfredo Rigalli

Authors
  1. Brenda Lorena Fina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maela Lupo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eugenia Rocío Da Ros
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mercedes Lombarte
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alfredo Rigalli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Brenda Lorena Fina.

Ethics declarations

The animals were treated according to the accepted international standards for animal care, and the study has been approved by the Ethical Committee of the School of Medicine of Rosario National University.

Conflict of Interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fina, B.L., Lupo, M., Da Ros, E.R. et al. Bone Strength in Growing Rats Treated with Fluoride: a Multi-dose Histomorphometric, Biomechanical and Densitometric Study. Biol Trace Elem Res 185, 375–383 (2018). https://doi.org/10.1007/s12011-017-1229-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-017-1229-2

Keywords

Search

Navigation