What determines peak bone mass and bone loss?

Bone mass at any point in life represents a balance between the amount of bone laid down during growth and development and the amount of bone lost with ageing. At a cellular level, these changes in bone mass occur as the result of bone remodelling; a process whereby bone resorbing cells (osteoclasts) and bone forming cells (osteoblasts) remove and replace small packets of bone at discrete points throughout the skeleton. This process is in turn regulated by a complex interaction between genetic factors and environmental influences such as nutrition and exercise, which affect bone cell function both directly and indirectly by altering the production of local and systemic hormones that modulate bone cell activity. In this chapter, I shall review the relative importance of genetic and environmental factors in regulating bone growth, peak bone mass, and bone loss. Discussion of the genetic aspects shall focus on recent data linking polymorphisms in candidate genes to bone mass and bone loss, and on the possible role which gene-environment interactions may have in regulating these processes.