Bone remodelling.

Bone is a specialised connective tissue that, together with cartilage, makes up the skeleton. These tissues serve three functions: (a) mechanical support and site of muscle attachment for locomotion; (b) protection for vital organs and bone marrow and (c) a metabolic reserve of ions for the entire organism, especially calcium and phosphate. The fundamental constituents are the cells and a calcified extracellular matrix. The latter is particularly abundant and is composed of collagen fibres and a ground substance rich in glycosaminoglycans. The osteoclasts and osteoblasts have evolved to regulate the growth and turnover of bone and mediate ion fluxes between the bone and blood. The osteoclasts solubilise the mineralised organic matrix, and the osteoblasts are capable of forming bone and synthesising the various structural proteins and growth factors. Except during growth, a balance between bone resorption and formation is maintained. The activities of the bone formation and resorbing cells are regulated by local and systemic humoral factors, such as parathyroid hormone, cytokines, 1,25,dihydroxy vitamin D3 and the eicosanoids. Any dysfunction of either the local or systemic regulatory systems will lead to pathological changes in the rate of bone formation or resorption and ultimately a clinical disease of the skeleton.