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J Trace Elem Med Biol. 2017 Jan;39:140-146. doi: 10.1016/j.jtemb.2016.09.007. Epub 2016 Sep 23.

Effects of fluoride on insulin signaling and bone metabolism in ovariectomized rats.

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Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas-SBFis - Department of Basic Sciences - Araçatuba Dental School, UNESP - Univ Estadual Paulista, Rua José Bonifácio 1193. CEP 16015-050, Brazil.
Department of Child and Social Dentistry - Araçatuba Dental School, UNESP - Univ Estadual Paulista, Rua José Bonifácio 1193. CEP 16015-050, Brazil. Electronic address:


Fluoride is an essential trace element for the maintenance of bone health owing to its capacity to stimulate proliferation and osteoblastic activity that can lead to increased bone formation. However, excessive sodium fluoride (NaF) intake can impair carbohydrate metabolism thereby promoting hyperglycemia, insulin resistance, and changes in insulin signaling. Thus, this study aimed to evaluate the effect of chronic treatment with NaF in bone metabolism, insulin signaling, and plasma concentrations of glucose, insulin, tumor necrosis factor-α (TNF-α), osteocalcin (OCN), and fluoride in ovariectomized rats. Thirty-two ovariectomized Wistar rats were randomly distributed into two groups: Control (OVX-C) and those undergoing treatment with NaF (50mg F/L) in drinking water for 42days (OVX-F). Glucose and insulin levels were assessed, followed by homeostasis model assessment of insulin resistance (HOMA-IR). Akt serine phosphorylation was evaluated by western blotting. Plasma concentrations of TNF-α and OCN were evaluated by ELISA. The left and right tibia was collected for immunohistochemical and histomorphometric analysis, respectively. Chronic treatment with NaF promoted insulin resistance, decreased insulin signal, increased plasma concentration of insulin, fluoride, OCN and TNF-α, decreased trabecular bone area of the tibia, and caused changes in bone metabolism markers in ovariectomized rats. These results suggest the need for caution in the use of NaF for the treatment of osteoporosis, especially in postmenopausal woman.


Bone loss; Fluoride; Insulin resistance; Osteoporosis

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