The "Mechanostat" Principle and the Osteoprotegerin-OPG/RANKL/RANK System PART II. The Role of the Hypothalamic-Pituitary Axis.

Recent literature provides us with the indication that the ratio of OPG/RANKL concentrations fluctuate in a non-linear (bell-shaped) mode, according to Frost's "mechanostat" theory, during the application of mechanical strain. A similar cellular signal transduction mechanism to mechanical loading, that may also regulate bone resorptive activities, has nowdays been proposed. Since the skeleton is considered to be an endocrine organ, as such, it may likewise be subject to hypothalamic control. This central regulatory system may continually modulate the adaptation of the bone homeostatic system to external challenges. The hypothalamic-pituitary-gonadal axis may play a role in the regulation of OPG/RANKL secretion. The "mechanostat" principle may well characterize the oscillatory properties of the signal transduction mechanism that controls hard tissue metabolism and includes biochemical apart from mechanical stimuli. J. Cell. Biochem. 118: 962-966, 2017.