The "soft" side of the bone: unveiling its endocrine functions

Bone has always been regarded as a merely structural tissue, a "hard" scaffold protecting all of its "soft" fellows, while they did the rest of the work. In the last few decades this concept has totally changed, and new findings are starting to portray bone as a very talkative tissue that is capable not only of being regulated, but also of regulating other organs. In this review we aim to discuss the endocrine regulation that bone has over whole-body homeostasis, with emphasis on energy metabolism, male fertility, cognitive functions and phosphate (Pi) metabolism. These delicate tasks are mainly carried out by two known hormones, osteocalcin (Ocn) and fibroblast growth factor 23 (FGF23) and possibly other hormones that are yet to be found. The extreme plasticity and dynamicity of bone allows a very fine tuning over the actions these hormones exert, portraying this tissue as a full-fledged endocrine organ, in addition to its classical roles. In conclusion, our findings suggest that bone also has a "soft side", and is daily taking care of our entire organism in ways that were unknown until the last few years.