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Reducing Stress Fracture in Physically Active Military Women (1998)
Institute of Medicine (IOM)

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and resorption. Osteoblasts are derived from local bone marrow mesenchymal cells and are located on all bone surfaces where active bone formation is taking place (Cowin et al., 1991; Marks and Popoff, 1988). Their main function is to synthesize and secrete the organic matrix of bone. Once osteoblasts stop forming bone, they may either decrease their synthetic activity and remain on the surface of the bone where they are known as bone-lining cells, or they may surround themselves with matrix and become osteocytes. Bone-lining cells are elongated and contain fewer organelles than osteoblasts. The main role of these cells is to contract and secrete enzymes that remove the thin layer of osteoid covering the mineralized matrix. This allows osteoclasts to attach to bone and begin resorption (Buckwalter et al., 1996). Osteocytes comprise more than 90 percent of the bone cells in the mature human skeleton. They are connected to adjacent osteocytes, active osteoblasts, and bone lining cells by numerous cytoplasmic projections that travel in channels (canaliculi) through mineralized matrix (Boivin et al., 1990). These interconnections may allow the cells to sense deformation of bone by mechanical loads and to coordinate the remodeling process.

Osteoclasts are derived from extraskeletal, hematopoietic stem cells (Girasole et al., 1992). They are large, motile, multinucleated cells found on bone surfaces that are undergoing resorption. To resorb the bone matrix, osteoclasts bind to the bone surface and create an acidic environment by secreting proteins and enzymes (Peck and Woods, 1988).

The extracellular matrix of bone is comprised of both inorganic and organic components. The inorganic component contributes approximately 65 percent of the wet weight of bone and consists mainly of calcium and phosphate in crystals of hydroxyapatite (Boivin et al., 1990). Other ions within the bone matrix include carbonate, citrate, fluoride, and magnesium and chloride in much smaller quantities. The inorganic matrix of bone performs two essential functions: it serves as an ion reservoir, and it gives bone most of its strength and stiffness (Buckwalter et al., 1995). The organic components, comprising 20 percent of the wet weight of bone, are collagen fibrils and an interfibrillar ground substance composed of as many as 200 noncollagenous proteins including osteocalcin, osteonectin, osteopontin, and various glycoproteins. These organic constituents give bone its flexibility and resilience (Martin, 1991), and the matrix macromolecules appear to contribute to the structure and functional qualities of bone (Meghji, 1992). The majority of the organic matrix is produced by osteoblasts, the most abundant protein being type 1 collagen (Boivin et al., 1990). Collagen molecules are secreted as procollagen into the extracellular space. They are then assembled into fibrils that are arranged such that spaces exist between molecules to accommodate the calcium and phosphate crystals.

HORMONAL REGULATION OF BONE METABOLISM AND REMODELING

The dynamic processes involved in bone metabolism relate to the events associated with bone formation and bone resorption. The extent to which these two processes are in balance determines whether bone mass will be gained (in youth), conserved (in young adults), or lost (in middle-aged and older adults). As noted earlier, the cells involved in bone formation and bone resorption are the osteoblast and the osteoclast, respectively. Bone markers refer to biochemical moieties that result from the secretory products of these cells or from the formation or breakdown of type 1 collagen, the organic substrate upon which mineralization occurs.

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