Normal bone physiology, remodelling and its hormonal regulation

The skeleton has structural and locomotor functions, and is a mineral reservoir. Bone turnover by osteoclasts and osteoblasts is a lifelong process, incorporating growth, modelling and remodelling to repair microdamage and access the mineral reservoir. Signalling between bone cells is essential for the co-ordination of these processes. Osteoblasts regulate osteoclast activity through the RANK/RANK ligand/OPG system, and osteocytes regulate osteoblast activity through sclerostin secretion. If resorption and formation are balanced there is no net change in bone mass after each remodelling cycle, but with ageing and some disease states resorption exceeds formation, leading to negative bone balance, decreased bone mass and loss of microstructural integrity. The rate of remodelling is determined by factors including mechanical loading and endocrine influences. The most important endocrine regulator of bone turnover is oestrogen, but other hormones regulating bone metabolism include IGF-1, PTH and gut and adipocyte hormones.