Physiopathological basis of bone turnover.

Bone remodeling involves the continuous removal of bone (bone resorption) followed by synthesis of new bone matrix and subsequent mineralization (bone formation). The principal cells that mediate the boneforming processes of the skeleton are osteoblast cells. They are responsible for the production of the matrix constituents and the differentiation of osteoblasts from stromal cell precursors is stimulated by several hormonal and non-hormonal molecules. On the other hand, the osteoclasts are giant multinucleated cells responsible of bone resorption. They are formed in the bone marrow and mature cells are stimulated by PTH and locally acting agents such as transforming growth factor alpha (TGFalpha), tumor necrosis factor (TNF) interleukin 1 (IL-1) and interleukin 6 (IL-6). The first events during bone remodeling is osteoclast activation, followed by osteoclast formation, polarization constitution of the ruffled border, resorption and ultimately apoptosis. Osteoclast apoptosis is followed by a series of sequential changes in cells in the osteoblast lineage, including osteoblast chemotaxis, proliferation and differentiation, which in turn is followed by formation of mineralized bone and cessation of osteoblast activity. The final phase of the formation process is cessation of osteoblast activity. The resorption lacunae are usually repaired either completely or almost completely. Understanding the sequence of cellular events may be important to better know the mechanisms responsible for bone loss that occurs in age and in several pathological conditions.