Physiopathological basis of bone turnover

Bone remodeling involves the continuous removal of bone (bone resorption) f ollowed by synthesis of new bone matrix and subsequent mineralization (bone formation). The principal cells that mediate the bone-forming processes of the skeleton are osteoblast cells. They are responsible for the production of the matrix constituents and the differentiation of osteoblasts from str omal cell precursors is stimulated by several hormonal and non-hormonal mol ecules. On the other hand, the osteoclasts are giant multinucleated cells r esponsible of bone resorption. They are formed in the bone marrow and matur e cells are stimulated by PTH and locally acting agents such as transformin g growth factor alpha (TGF alpha), 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 co nstitution of the ruffled border, resorption and ultimately apoptosis. Oste oclast 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 pro cess is cessation of osteoblast activity. The resorption lacunae are usuall y repaired either completely or almost completely. Understanding the sequen ce of cellular events may be important to better know the mechanisms respon sible for bone loss that occurs in age and in several pathological conditio ns.