title: Effect of Sodium Fluoride on Bone Biomechanical and Histomorphometric Parameters and on Insulin Signaling and Insulin Sensitivity in Ovariectomized Rats.
abstract: 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.
authors.affiliation: Ciências Fisiológicas-SBFis, Department of Basic Sciences, Araçatuba Dental School, UNESP-Univ Estadual Paulista, Rua José Bonifácio 1193, Araçatuba, CEP 16015-050, Brazil.
authors.forename: Rita
authors.initials: R
authors.lastname: de Cássia Alves Nunes
authors.affiliation: Department of Child and Social Dentistry, Araçatuba Dental School, UNESP-Univ Estadual Paulista, Rua José Bonifácio 1193., Araçatuba, CEP 16015-050, Brazil.
authors.forename: Fernando Yamamoto
authors.initials: FY
authors.lastname: Chiba
authors.affiliation: Ciências Fisiológicas-SBFis, Department of Basic Sciences, Araçatuba Dental School, UNESP-Univ Estadual Paulista, Rua José Bonifácio 1193, Araçatuba, CEP 16015-050, Brazil.
authors.forename: Amanda Gomes
authors.initials: AG
authors.lastname: Pereira
authors.affiliation: Ciências Fisiológicas-SBFis, Department of Basic Sciences, Araçatuba Dental School, UNESP-Univ Estadual Paulista, Rua José Bonifácio 1193, Araçatuba, CEP 16015-050, Brazil.
authors.forename: Renato Felipe
authors.initials: RF
authors.lastname: Pereira
authors.affiliation: Ciências Fisiológicas-SBFis, Department of Basic Sciences, Araçatuba Dental School, UNESP-Univ Estadual Paulista, Rua José Bonifácio 1193, Araçatuba, CEP 16015-050, Brazil.
authors.forename: Maria Sara
authors.initials: MS
authors.lastname: de Lima Coutinho Mattera
authors.affiliation: Ciências Fisiológicas-SBFis, Department of Basic Sciences, Araçatuba Dental School, UNESP-Univ Estadual Paulista, Rua José Bonifácio 1193, Araçatuba, CEP 16015-050, Brazil.
authors.forename: Edilson
authors.initials: E
authors.lastname: Ervolino
authors.affiliation: Department of Support, Animal Production and Health, Araçatuba School of Veterinary Medicine, UNESP-Univ Estadual Paulista, Rua Clóvis Pestana, 793., Araçatuba, CEP 16050-680, Brazil.
authors.forename: Mário Jefferson Quirino
authors.initials: MJ
authors.lastname: Louzada
authors.affiliation: Department of Biological Sciences, Bauru Dental School, University of São Paulo, Alameda Octávio Pinheiro Brisolla, 9-75, Bauru, São Paulo, 17012-901, Brazil.
authors.forename: Marília Afonso Rabelo
authors.initials: MA
authors.lastname: Buzalaf
authors.affiliation: Ciências Fisiológicas-SBFis, Department of Basic Sciences, Araçatuba Dental School, UNESP-Univ Estadual Paulista, Rua José Bonifácio 1193, Araçatuba, CEP 16015-050, Brazil.
authors.forename: Cristina Antoniali
authors.initials: CA
authors.lastname: Silva
authors.affiliation: Ciências Fisiológicas-SBFis, Department of Basic Sciences, Araçatuba Dental School, UNESP-Univ Estadual Paulista, Rua José Bonifácio 1193, Araçatuba, CEP 16015-050, Brazil. dorishs@foa.unesp.br.
authors.forename: Doris Hissako
authors.initials: DH
authors.lastname: Sumida
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D005260:Female; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D010024:Osteoporosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D012969:Sodium Fluoride / Q000494:pharmacology*; D013977:Tibia / Q000378:metabolism / Q000473:pathology
chemical_list: D007328:Insulin; D012969:Sodium Fluoride
keywords: Bone density; Fluoride; Insulin resistance; Osteoporosis; Rats