During the first few years of the twenty-first century, the complex mechanisms that characterise the control of bone remodelling were just beginning to be recognised and starting to be investigated. Results of the overwhelming amount of research subsequently published have illuminated the extreme complexity of the cellular and molecular interactions as well as the network of interwoven highways and byways representing the numerous pathways that transport factors to stimulate or to inhibit specific cellular activities. A highly significant aspect of the results of these investigations is the unequivocal demonstration of the participation of many of these pathways not only in the control of bone remodelling but also in numerous processes—both physiological and pathological—involving other organs and tissues and as such are examples of systems biology.