Bone at the tissue level undergoes remodeling: it is continuously being resorbed and rebuilt (or formed). A negative balance between bone resorption and formation, frequently due to excessive resorption, is the basis of many bone diseases. Resorption is carried out by osteoclasts, which are specialized multinucleated cells of hemopoietic origin. Bone resorption takes place at a specialized area of the osteoclast cell membrane called "ruffled border," which comprises a sealed lysosomal compartment where the acidic pH solubilizes the mineral and the proteolytic enzymes digest the matrix. Among the agents that inhibit bone resorption, only calcitonin and bisphosphonate have been shown to act directly on osteoclasts. Other hormones and agents, which modulate bone turnover, probably act on the osteoblasts or cells of the osteoblast lineage. Osteoblasts are bone-forming cells, originating from cells resident in bone committed to the osteoblastic lineage. They synthesize and secrete most of the proteins of the bone matrix, including type I collagen and non-collagenous proteins. They possess high levels of alkaline phosphatase, which participates in mineralization. Proteins, produced by osteoblasts, spill over into the blood and are used as indicators of bone formation. In addition to the matrix-forming ability, cells of the osteoblastic family (osteocytes, lining cells, and maybe other cells) participate in the regulation of bone turnover. They respond to parathyroid hormone, glucocorticoids, vitamin D, sex steroids, insulin, prostaglandins, growth factors, and so on. There are a significant number of cytokines, that are locally produced and may control bone resorption. These include prostaglandins, IL1, TNF-alpha, possibily IL6. Osteoblastic cells also produce some, and respond to many, growth factors that have been implicated in bone development, bone remodeling, and repair. Cells of the osteoblastic lineage probably also mediate the skeletal response to mechanical forces.
