Dynamics of bone remodelling: biochemical and pathophysiological basis.

Renewal of the bone matrix is induced by bone cells called osteoblasts and osteoclasts, which act sequentially on the bone surface. This "remodelling" depends on local factors, such as cytokines and growth factors which play an important role in the bone tissue as mediators of cell-to-cell and matrix-to-cell communication. Growth factors released from the bone matrix during the resorption are responsible for the refilling of the resorption cavity by osteoblasts. Cytokines also mediate locally the effect of several hormones on bone cells. Recent work is concerned with the modulation by oestradiol of osteoblastic cytokines acting on osteoclast differentiation. In mice, an increased production of interleukin-6 production by osteoblasts is responsible for the increased bone resorption occurring after ovariectomy. Other growth factors, such as transforming growth factor-beta, whose secretion is modified by oestradiol, may also be implicated. In women, an increase in cytokine production by blood mononuclear cells is associated with the occurence of menopause and reversed by oestrogen treatment. During osteoporosis and age-related bone changes, changes in the production of insulin-like growth factor I or of one of its binding proteins could be responsible for low bone formation. In addition to their role in bone remodelling, cytokines and growth factors are now implicated in osteoporosis.