Uncovering the links between osteoporosis and diabetes

Abstract

Introduction: Using an animal model for osteopenia to describe the distribution of Lead (Pb) throughout the body, we have reported that ovariectomized animals had significantly lower serum osteocalcin (OC) levels and higher, although nonsignificant, serum C-terminal peptide-bound crosslinks of collagen (CTX) levels than intact animals [1]. Here we present unpublished data on concentrations of elements of interest (Ca, Cl, Fe, K, Na and Pb) in hard and soft tissues of the same animals, to uncover the links between osteoporosis and diabetes. The model makes it feasible to investigate such links, therefore the appropriateness of this approach is not only warranted but also justified by the 3RS principle for the use of animals in research. Materials and methods: The animal study was approved by the Ethics Committee of ISCSEM and was conducted following the Portuguese Law and EU Directive 2010/63/EU, in a licensed animal facility. Two groups of adult female Wistar rats of the same age were considered: normal intact rats (n = 7); and OVX animals (n = 7) ovariectomized between the 11th and 12th week of age. From age 6-months on, all animals received the same dose of Pb acetate in water (500 ppm) for 6 months. Tissues collected for analysis included lumbar vertebrae and femora bones, as well as blood and liver. The concentration of elements of interest in hard and soft tissues was determined by Wavelength Dispersive X Ray Fluorescence (WDXRF) spectroscopy, using a 4kW commercial spectrometer (S4 Pioneer, Bruker AXS). Multivariate analysis of variance (MANOVA) was used in group comparisons, given the multiple correlations between elemental concentrations. Results: MANOVA methods show that OVX animals have significantly higher liver Cl, Na and Ca concentrations, whereas normal animals show significantly higher liver Pb and K concentrations, with observed power of 91.0%. Significantly lower serum OC levels were observed in the OVX group, with observed power of 72.7%, with no differences between groups for CTX levels. Lower Ca content was strongly suggested for trabecular bone of OVX animals. Discussion and conclusions: Significant differences in hepatic Ca concentration between OVX and normal animals suggest that Ca signalling mechanisms regulating gluconeogenesis, through modulation of hormones such as glucagon, insulin, vasopressin and adrenalin [2,3], may occur differently in the two groups. Moreover, since extracellular concentrations of cations such as K and Na markedly affect the hormonal activity effects on gluconeogenesis [4], the observed differences in the hepatic concentrations of such elements between the groups may further increase differences in gluconeogenesis in the two groups. Therefore, we postulated that bone turnover changes may impact on gluconeogenesis, which launched the basis for another research project linking osteoporosis to diabetes, nearly concluded in our laboratory.