Fundamental limits on longitudinal bone growth: growth plate senescence and epiphyseal fusion.

Longitudinal bone growth occurs rapidly in early life but then slows and, eventually, ceases. The decline in growth rate is caused primarily by a decrease in the rate of chondrocyte proliferation and is accompanied by structural changes in growth plate cartilage. This programmed senescence does not appear to be caused by hormonal or other systemic mechanisms but is intrinsic to the growth plate itself. In particular, recent evidence indicates that senescence might occur because stem-like cells in the resting zone have a finite proliferative capacity, which is exhausted gradually. In some mammals, including humans, proliferative exhaustion is followed by epiphyseal fusion, an abrupt event in which the growth plate cartilage is replaced completely by bone.