Fig. 1.

a Remodelling of bone is controlled by osteoblasts and osteoclasts. Bone formation happens through organic matrix formation (osteoid), that gets mineralised to form bone, and finally undergoes remodelling by resorption and reformation. Calcium and phosphate form hydroxyapatite that deposits in the extracellular compartment, between collagen fibres. Osteoclasts are responsible for bone resorption, removing bone minerals and matrix. Certain biochemical markers reflect bone turnover and bone cell activity. Bone regulators can be grouped broadly into bone turnover factors (e.g. PTH, sclerostin) and bone cell activity indicators (bone formation, e.g. bone-specific alkaline phosphatase (BSAP), osteocalcin (OC), procollagen type I N propeptide (PINP), procollagen type I C propeptide (PICP); bone resorption, e.g. carboxyterminal cross-linking telopeptide of bone collagen (CTX), tartrate-resistant acid phosphatase (TRAP5b)). b Bone resorption is activated by the RANK-RANKL-OPG pathway, which regulates osteoclast differentiation and activation. 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 decoy receptor for RANKL, neutralising the osteoclastic function activated by the RANKL-RANK complex. Thus, the RANKL/OPG ratio is an important determinant of bone mass as it affects mineralisation, alkaline phosphatase, Runx2 and osteocalcin which reflect osteoblast differentiation and bone formation rate. Figure adapted from Charoenphandhu et al. [117]