Effect of training on bone quality in rats with insulin resistance induce by fluoride consumption.

When large amounts of Fluoride are consumed produces insulin resistance, but exercise can reverse insulin resistance in rats, because of a high fluoride uptake by bone tissue. However, bone quality has not been studied in those experiments. Therefore, the aim of this work was to evaluate bone quality in rats treated with fluoride when performing exercise. Sprague-Dawley rats were divided into 3 groups (n=6 per group): Control (drinking water without fluoride), Fluoride (drinking water with fluoride 15 mg/L for 30 days) and Exercise (daily running on a treadmill and drinking water with fluoride 15 mg/L for 30 days).  Then, bone mineral density, mechanical and histological properties and bone fluoride level were measured. No effect of treatment on any bone parameters were observed. These results indicate that exercise normalizes glucose metabolism in insulin-resistant rats by bone fluoride uptake; however, this increase in bone fluoride does not manifest in bone deterioration.

Cuando se consumen grandes cantidades de fluoruro se produce resistencia a la insulina, pero la realización de ejercicio puede revertir dicho efecto en ratas, debido a una alta absorción de fluoruro por el tejido óseo. Sin embargo, la calidad ósea no ha sido estudiada. Por ello, el objetivo de este trabajo fue evaluar la calidad ósea en ratas tratadas con flúor que realizan ejercicio. Se trabajó con ratas Sprague-Dawley que se dividieron en 3 grupos (n=6 por grupo): Control (recibiron agua sin flúor), Flúor (recibieron agua con flúor 15 mg/L durante 30 días) y Ejercicio (realizaron ejercicio diariamente en cinta ergométrica y recibieron agua con fluoruro 15 mg/L por 30 días). Luego, se midieron la densidad mineral ósea, las propiedades biomecánicas e histológicas y el nivel de fluoruro óseo. No se observó ningún efecto del tratamiento sobre ningún parámetro óseo. Estos resultados indican que el ejercicio normaliza el metabolismo de la glucosa en ratas resistentes a la insulina mediante la captación ósea de fluoruro; sin embargo, este aumento del fluoruro óseo no se manifiesta en deterioro óseo.

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

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.

Methodology developed for the simultaneous measurement of bone formation and bone resorption in rats based on the pharmacokinetics of fluoride.

This paper describes a novel methodology for the simultaneous estimation of bone formation (BF) and resorption (BR) in rats using fluoride as a nonradioactive bone-seeker ion. The pharmacokinetics of flouride have been extensively studied in rats; its constants have all been characterized. This knowledge was the cornerstone for the underlying mathematical model that we used to measure bone fluoride uptake and elimination rate after a dose of fluoride. Bone resorption and formation were estimated by bone fluoride uptake and elimination rate, respectively. ROC analysis showed that sensitivity, specificity and area under the ROC curve were not different from deoxypiridinoline and bone alkaline phosphatase, well-known bone markers. Sprague-Dawley rats with modified bone remodelling (ovariectomy, hyper, and hypocalcic diet, antiresorptive treatment) were used to validate the values obtained with this methodology. The results of BF and BR obtained with this technique were as expected for each biological model. Although the method should be performed under general anesthesia, it has several advantages: simultaneous measurement of BR and BF, low cost, and the use of compounds with no expiration date.

Fluoride increases superoxide production and impairs the respiratory chain in ROS 17/2.8 osteoblastic cells.

It is known that fluoride produces oxidative stress. Inflammation in bone tissue and an impairment of the respiratory chain of liver have been described in treatments with fluoride. Whether the impairment of the respiratory chain and oxidative stress are related is not known. The aim of this work was to study the effects of fluoride on the production of superoxide radical, the function of the respiratory chain and the increase in oxidative stress in ROS 17/2.8 osteoblastic cells. We measured the effect of fluoride (100 µM) on superoxide production, oxygen consumption, lipid peroxidation and antioxidant enzymes activities of cultured cells following the treatment with fluoride. Fluoride decreased oxygen consumption and increased superoxide production immediately after its addition. Furthermore, chronic treatment with fluoride increased oxidative stress status in osteoblastic cells. These results indicate that fluoride could damage bone tissue by inhibiting the respiratory chain, increasing the production of superoxide radicals and thus of the others reactive oxygen species.