Proceedings of The Physiological Society

King's College London (2009) Proc Physiol Soc 14, SA10

Research Symposium

Regulation of bone mass and architecture by mechanical and biochemical interactions.

T. Skerry1

1. Human Metabolism, Univesity of Sheffield, Sheffield, United Kingdom.

The strength of the skeleton is dependent on its mass, architecture and material properties. As we all differ in the demands we place on our skeletons, it is reasonable that we each tune our bone strength to our individual requirements. This provides the lightest structure to incur minimal costs of growth, maintenance and use with an adequate safety factor. At first impression, it seems that a relatively simple mechansm could account for the influence of mechanical forces on bone. However this is not so. The way that the skeleton responds to different forms of exercise/loading, and the different responses in different skeletal sites, and with age and sex show that this is a very complex system. Further complexity is added by the interactions of mechanical and other biochemical influences which are regulated by competing physiological demands. The effects of these interactions are to regulate dynamically the mass and architecture of each bone. In general the material properties do not appear to be regulated by adaptive mechanisms but are specified for each skeletal site during development. The alteration of bone strength therefore depends upon orchestration of the actions of populations of bone forming osteoblasts and bone resorbing osteoclasts, in order to form or remove bone in a way that is appropriate for function. The regulation of bone formation and resorption by those effector cells is likely to involve osteocytes, which are in an ideal position to sense and signal onwards the mechanical requirements of a region of bone. In recent years, interest in osteocyte biology has grown considerably. However while the specific signalling events induced in osteocytic cells after loading have increased knowledge in the area, there is still a gap in understanding of how complex physiological loading (as opposed to simple modelled stretching) influences cells differently, and how these effects interact with other osteotropic influences. The ability of the skeleton to retain information on the effect of previous loading, and to modify the response to subsequent events is particularly poorly understood, yet may represent an important part of the way that age related changes occur in bone. Our studies suggest that a signalling system involving the excitatory amino acid glutamate and utilising synapse-like communications betweeen cells could provide this memory-like function in bone. Improved understanding in these areas is likely to have pervasive implications in our ailiity to prevent or treat bone loss in the elderly.

Where applicable, experiments conform with Society ethical requirements