Fig. 1.

A schematic diagram of the normal bone mineralization process. Osteoblasts produce type 1 collagen which becomes the scaffolding around which mineralization occurs to form the osteoid. Osteoblastic differentiation is mainly regulated by the Wnt signalling pathway. Hormones such as PTH and vitamin D regulate this process. Secretory calcium-binding phosphoproteins (SCPPs), such as osteonectin, bind to hydroxyapatite and Type 1 collagen. Other SCPPs are osteopontin and bone sialoprotein which are used as a focus for mineral crystal formation. Osteoclasts control bone resorption. Mature osteoclasts bind to bone matrix and secrete lysozymal enzymes to then release calcium and phosphate into the serum. Resorption is activated by the RANK–RANKL–OPG pathway. Osteoclast precursors express RANK, which is activated by its ligand, RANKL, produced by osteoblasts and osteocytes. Osteoprotegerin (OPG), also a product of osteoblasts and osteocytes, is a competitor receptor for RANKL with the opposite effect of neutralising and pausing the osteoclastic function activated by the RANKL–RANK complex. Osteocytes are terminally differentiated osteoblasts, embedded in mineralised osteoid. Osteocytes upregulate osteoblasts through nitric oxide and prostaglandin E2 production or downregulate them through sclerostin secretion