Regulation of bone formation by bone morphogenetic proteins and other growth factors.

Bone formation in adult humans is a complex and closely regulated process. It usually occurs at sites of previous osteoclastic bone resorption. It also may occur in the growing long bones during endochondral bone formation, and appositional bone formation also can appear during growth and adolescence without prior local resorption, particularly on periosteal surfaces. The cellular events involved in bone formation include chemotaxis of osteoblast precursors; proliferation of committed osteoblast precursors; differentiation, including expression of growth regulatory factors and the structural proteins of bone, such as osteocalcin, osteopontin, and Type I collagen; and mineralization. It is clear that these cellular events must be under very tight regulatory control. They may all be modulated by systemic hormones, including the calciotropic hormones, parathyroid hormone and 1,25 dihydroxyvitamin D and other systemic hormones, such as the pituitary and thyroid hormones and sex steroids, but probably are modulated predominantly by local factors or cytokines generated in the bone cell microenvironment.