Further evidence that FSH causes bone loss independently of low estrogen

Bone-brain crosstalk and potential associated diseases

“…However, the importance of the nervous system on bone physiology and turnover has begun to be deciphered over the past 15 years [18,33,34,36] and there is now strong data showing that the brain is a powerful regulator of skeletal homeostasis via numerous players and pathways. Indeed, the CNS regulates bone mass either by the direct action of neurotransmitters that it produces or by acting as a mediator in processing peripheral hormonal signals, such as leptin, that originates from adipose tissue.…”

“…Although in vitro studies have shown that leptin, under certain conditions, can affect osteoblast functions directly [47], several genetic pieces of evidence indicate that leptin acts on the CNS to inhibit the accrual of bone mass, which is consistent with other described functions of leptin. The most convincing argument is that neuron-specific deletion of the leptin receptor [46] recapitulates the bone phenotype of ob/ob mice whereas an osteoblast-specific deletion does not [18,48]. Moreover, intra-cerebro-ventricular (ICV) infusions of leptin decreased bone mass and volume by decreasing osteoblast activity.…”

“…This is particularly true for the bone for which multiple genetic-based studies have shed light on the growing physiological importance of this organ in whole-body homeostasis [17][18][19]. Beyond the classical view of the skeleton describing it as a relatively static tissue, the bone secretes at least two molecules influencing whole-body homeostasis [18,[20][21][22][23][24]. First, fibroblast growth factor 23 (FGF23), a protein synthesized by osteoblasts and osteocytes and released into general circulation, regulates phosphocalcic metabolism in multiple tissues [21,25,26].…”

“…Second, it was shown that an osteoblast-derived molecule, osteocalcin (Ocn), does not act directly on bone but influences other physiological functions that in turn influences bone physiology. Indeed, Ocn promotes pancreatic β-cells proliferation, glucose homeostasis, enhances energy expenditure and prevents the appearance of glucose intolerance induced by high fat diet [18,23,27,28]. Moreover, it was shown that Ocn may also influence the gonads by promoting testosterone biosynthesis in Leydig cells of the testis and thereby favors male fertility [18,22,[29][30][31][32].…”

“…Indeed, Ocn promotes pancreatic β-cells proliferation, glucose homeostasis, enhances energy expenditure and prevents the appearance of glucose intolerance induced by high fat diet [18,23,27,28]. Moreover, it was shown that Ocn may also influence the gonads by promoting testosterone biosynthesis in Leydig cells of the testis and thereby favors male fertility [18,22,[29][30][31][32]. The demonstration that bone affects such a variety of physiological functions suggests that the skeleton has important endocrine functions and leads us to ask how bone and bone derived factors influence other organs.…”