Biological Trace Element Research

, Volume 173, Issue 1, pp 144–153 | Cite as

Effect of Sodium Fluoride on Bone Biomechanical and Histomorphometric Parameters and on Insulin Signaling and Insulin Sensitivity in Ovariectomized Rats

  • Rita de Cássia Alves Nunes
  • Fernando Yamamoto Chiba
  • Amanda Gomes Pereira
  • Renato Felipe Pereira
  • Maria Sara de Lima Coutinho Mattera
  • Edilson Ervolino
  • Mário Jefferson Quirino Louzada
  • Marília Afonso Rabelo Buzalaf
  • Cristina Antoniali Silva
  • Doris Hissako SumidaEmail author


Osteoporosis is a systemic disease characterized by bone degradation and decreased bone mass that promotes increased bone fragility and eventual fracture risk. Studies have investigated the use of sodium fluoride (NaF) for the treatment of osteoporosis. However, fluoride can alter glucose homeostasis. The aim of this study was to evaluate the effects of NaF intake (50 mg/L) from water on the following parameters of ovariectomized (OVX) rats: (1) tyrosine phosphorylation status of insulin receptor substrate (pp185 (IRS-1/IRS-2)) in white adipose tissue; (2) insulin sensitivity; (3) plasma concentrations of glucose, insulin, total cholesterol, triglyceride, TNF-α, IL-6, osteocalcin, calcium, and fluoride; (4) bone density and biomechanical properties in the tibia; and (5) tibia histomorphometric analysis. Fifty-two Wistar rats (2 months old) were ovariectomized and distributed into two groups: control group (OVX-C) and NaF group (OVX-F), which was subjected to treatment with NaF (50 mg/L) administered in drinking water for 42 days. The chronic treatment with NaF promoted (1) a decrease in pp185 (IRS-1/IRS-2) tyrosine phosphorylation status after insulin infusion in white adipose tissue and in insulin sensitivity; (2) an increase in the plasma concentration of insulin, fluoride, osteocalcin, calcium, triglyceride, VLDL-cholesterol, TNF-α, and IL-6; (3) a reduction in the trabecular width, bone area, stiffness, maximum strength, and tenacity; (4) no changes in body weight, food and water intake, plasma glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, bone mineral content, and bone mineral density. It was concluded that chronic treatment with NaF (50 mg/L) in OVX rats causes a decrease in insulin sensitivity, insulin signaling transduction, and biochemical, biomechanical, and histomorphometric bone parameters.


Fluoride Bone density Osteoporosis Insulin resistance Rats 



This work was supported by funds from the Coordination of Improvement of Higher Education Personnel (CAPES), Pro-rector for research, and graduate of UNESP– Univ Estadual Paulista, Brazil.

Compliance with Ethical Standards

Conflicts of interest

The authors declare that they have no conflicts of interest.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Rita de Cássia Alves Nunes
    • 1
  • Fernando Yamamoto Chiba
    • 2
  • Amanda Gomes Pereira
    • 1
  • Renato Felipe Pereira
    • 1
  • Maria Sara de Lima Coutinho Mattera
    • 1
  • Edilson Ervolino
    • 1
  • Mário Jefferson Quirino Louzada
    • 3
  • Marília Afonso Rabelo Buzalaf
    • 4
  • Cristina Antoniali Silva
    • 1
  • Doris Hissako Sumida
    • 1
    Email author
  1. 1.Ciências Fisiológicas-SBFis, Department of Basic Sciences, Araçatuba Dental SchoolUNESP-Univ Estadual PaulistaAraçatubaBrazil
  2. 2.Department of Child and Social Dentistry, Araçatuba Dental SchoolUNESP-Univ Estadual PaulistaAraçatubaBrazil
  3. 3.Department of Support, Animal Production and Health, Araçatuba School of Veterinary MedicineUNESP-Univ Estadual PaulistaAraçatubaBrazil
  4. 4.Department of Biological Sciences, Bauru Dental SchoolUniversity of São PauloBauruBrazil

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