How Cells Communicate in the Bone Remodelling Process.

Abstract

In the adult human skeleton, approximately 5 to 10% of the existing bone is replaced every year by bone remodelling. The remodelling process, which continues throughout adult life, provides for the calcium homeostatic system and is essential for resorptive removal of old bone, the removal and repair of micro-damage, and for the adaptation to mechanical stress[1,2]. The cellular sequence is initiated with signals that lead to osteoclast development and bone resorption (Fig. 1). How those signals are initiated is uncertain. In the case of micro-damage, this is proposed to lead to apoptosis of osteocytes that transmit signals to surface cells to promote production of receptor activator of NFκB ligand (RANKL) and hence osteoclast production[3]. Remodelling is essential for the maintenance of skeletal material and structural strength, with bone being continuously resorbed and reformed at about 1~2 million microscopic remodelling foci per adult skeleton. This sequence of events is initiated asynchronously throughout the skeleton, at sites that are geographically and chronologically separated from each other. Both bone resorption and bone formation occur at the same place in these “basic multicellular units” (BMUs), so that there is no change in the shape of the bone[4]. Within each of these BMUs, focal resorption is carried out by haemopoietically-derived osteoclasts and takes about 3 weeks per site, whereas the refilling of lost bone by osteoblasts, derived from bone marrow stromal cells and circulating precursors, takes about 3~4 months. In addition to remodelling, bone modelling on its periosteal surface is characterised by bone formation without prior bone resorption. This process, so vigorous during growth, establishes the adult size and shape of bone. At the completion of linear growth with closure of the epiphyses, periosteal apposition continues but markedly less so[5]. Tight regulation of these processes is essential for the achievement and maintenance of skeletal strength. Modelling and remodelling during growth achieves peak bone strength, and continued remodelling during adulthood maintains the mechanical integrity of the skeleton. Circulating hormones contribute, but the key influences are locally generated cytokines that are the signals mediating information transfer among osteoblasts, osteoclasts, immune cells and constituents of the bone matrix. How Cells Communicate in the Bone Remodelling Process