Bone is now regarded to be a key regulator of a number of metabolic processes, in addition to the regulation of mineral metabolism. However, our understanding of complex bone metabolic interactions at a systems level remains rudimentary. In vitro molecular biology and bioinformatics approaches have frequently been used to understand the mechanistic changes underlying disease at the cell level, however, these approaches lack the capability to interrogate dynamic multi-bone metabolic interactions in vivo. Here we present a novel and integrative approach to understand complex bone metabolic interactions in vivo using total-body positron emission tomography (PET) network analysis of murine 18F-FDG scans, as a biomarker of glucose metabolism in bones. In this report we show that different bones within the skeleton have a unique glucose metabolism and form a complex metabolic network, which could not be identified using single tissue simplistic PET standard uptake values analysis. The application of our approach could reveal new physiological and pathological tissue interactions beyond skeletal metabolism, due to PET radiotracers diversity and the advent of clinical total-body PET systems.