[Interconnection of morpho-functional changes at various levels of the cortical bone hierarchic organization in...

The authors define two groups of levels of cortical bone hierarchic organization. The first three levels (molecular, supra-molecular and tissue) are characterized by age-dependent changes in connections and geometry of collagen fibers, deviations in orientation and interaction between collagen and minerals, increase in crystallinity and size of the latter, resulting in matrix hypermineralization. It causes water and organic fraction displacement, as well as intermolecular space reduction, which provides for lesser amount of matrix deformations under the influence of mechanical forces. At the next three levels (structural-functional, organ-forming structures, organ) adaptation processes contribute to deformation increase due to a greater volume of cavities (Haversian canals and medullar cavity of the diaphysis of long tubular bones). These are due to the fact that osseous tissue cells possess superior and inferior thresholds of deformation perception, and through modeling/remodeling provide for extracellular matrix migration in the direction limited by these thresholds. Bone geometry changes leading to bone mass loss are also caused by age-dependent rise of the inferior threshold of sensitivity to mechanical impulses and decrease of muscle functional activity. Prevention of the described changes may be possible through elaboration of new, pathogenesis-based ways of drug therapy, including 1) osseous tissue mineralization reduction with the help of osteocyte pump regulators for predominant washing out of Ca2+, 2) lowering the threshold of electric impulses initiation arising in the osteocyte network under mechanical deformations.