Figure 1

The bone remodelling cycle. The bone remodelling cycle lasts 150–200 days and is primarily mediated by osteoblastic signals which promote the differentiation and maturation of osteoclast precursors. Activated osteoclasts create resorption pits with low pH to dissolve the inorganic matrix and lysomal enzymes, such as TRAP and cathepsin K, effectively digest the exposed type-1 collagen releasing specific degradation products. Osteoblasts are attracted to this eroded surface and begin to form new osteoid. Type-1 collagen, abundant in osteoblasts, is secreted as a procollagen precursor molecule into the extracellular space where it is cleaved at the amino- and carboxy-terminals releasing pro-peptides into the blood. Initially hydroxyapatite crystals are deposited in the osteoid then a slower mineralisation process continues over several months, followed by a period of quiescence. RANKL, an essential osteoclastogenic cytokine, is expressed on the surface of osteoblasts, it binds to its cellular receptor RANK on pre-osteoclasts and promotes their differentiation and activation. OPG a decoy receptor for RANKL, is secreted by osteoblasts and other stromal derived cells and reduces bone resorption by binding to RANK and preventing osteoclastic activity.