Bone and the regulation of glucose metabolism

Abstract

Introduction: Bone is a regulator of numerous metabolic processes that are independent of mineral metabolism [1]. The relationship between osteocalcin (OC), a bone-specific protein, and metabolic parameters, as glycaemia, insulin secretion and β-cell proliferation have been studied and implied the potential impact of the skeleton on energy regulation and glucose metabolism. Also, intermittent injections of OC have proven to improve glucose metabolism and prevent type 2 diabetes in mice [2]. Moreover, electrolyte disorders are observed in metabolic pathways involved in impaired energy metabolism and glycaemic regulation. Recent data associate the use of calcium and vitamin D supplementation to reduce the risk of Diabetes Mellitus (DM) [3]. The aim of the study was to investigate the long-term effects of altered bone turnover on glucose metabolism, using an animal model for osteopenia.

Materials and methods: Animal experiments were conducted at FMV/UTL, according to its ethics committee, Portuguese law and EU Directive 2010/63/EU. At baseline, two groups of 25 adult female Wistar rats were gathered: control and ovariectomized (OVX). The surgery to induce osteopenia [4] was performed 1 month prior to baseline. At all timepoints, for 12 months, biomarkerś levels of bone turnover and diabetes control were determined by ELISA protocols. Additionally, after sample preparation, system calibration and validation, bone and liver tissues were analysed for their elemental composition by wavelength dispersive X-ray fluorescence (WDXRF) spectroscopy, using a 4 kW commercial system (Bruker S4 Pioneer).

Results: Here we report data of the 12 months of the protocol. OVX animals showed increased bone resorption and lower concentration of elements involved in the calcium metabolism (calcium, phosphorus and magnesium) in femurs, which are important features of bone strength. Although there is amplified bone resorption in OVX group, calcium does not accumulate in its hepatic parenchyma, as liver of OVX animals present Ca concentrations significantly lower than those of controls. These differences between OVX and control animals in bone metabolism and composition are concomitant with clear increases of serum glucose levels in the OVX group, following a time-dependent pattern for the observed differences. By contrast, much less marked differences between the groups were observed for serum insulin levels.

Discussion and conclusions: Increased bone resorption and lower bone mineral content leads to hyperglycaemia manifesting in a time dependent manner. Since these effects were observed almost from the onset of the protocol, the data suggest that the relationships between diseases characterized by increased bone turnover, such as osteoporosis, and by disrupted glucose metabolism, such as diabetes, can occur in early adulthood.

Acknowledgements

The authors acknowledge funding from Egas Moniz Cooperativa de Ensino Superior, CRL.