Estrogen and bone metabolism.

Estrogen plays an important role in the growth and maturation of bone as well as in the regulation of bone turnover in adult bone. During bone growth estrogen is needed for proper closure of epiphyseal growth plates both in females and in males. Also in young skeleton estrogen deficiency leads to increased osteoclast formation and enhanced bone resorption. In menopause estrogen deficiency induces cancellous as well as cortical bone loss. Highly increased bone resorption in cancellous bone leads to general bone loss and destruction of local architecture because of penetrative resorption and microfractures. In cortical bone the first response of estrogen withdrawal is enhanced endocortical resorption. Later, also intracortical porosity increases. These lead to decreased bone mass, disturbed architecture and reduced bone strength. At cellular level in bone estrogen inhibits differentiation of osteoclasts thus decreasing their number and reducing the amount of active remodeling units. This effect is probably mediated through some cytokines, IL-1 and IL-6 being strongest candidates. Estrogen regulates the expression of IL-6 in bone marrow cells by a so far unknown mechanism. It is still uncertain if the effects of estrogen on osteoblasts is direct or is due to coupling phenomenon between bone formation to resorption.