Fig. 1: The stages of bone remodelling.

Bone remodelling is a process where cycles of bone resorption and formation are separated by periods of quiescence. During quiescence, the relatively inactive bone surface is lined by flat remnants of osteoblasts. Events such as hormone detection and/or mechanical loading can activate the recruitment of circulating osteoclast precursor cells. These precursor cells fuse to form premature osteoclasts and migrate to the bone surface, while bone lining cells retract to enable preosteoclast binding. Once bound to the bone matrix to form a sealing zone in the isolated area, they differentiate into mature osteoclasts for bone resorption. Mature osteoclasts secrete protons to create an acidic environment that dissolves bone mineral, and proteolytic enzymes to digest the bone matrix. The resorption process results in the formation of cavities, also known as Howship’s lacunae, beneath active osteoclasts. Osteoclasts undergo apoptosis once these cavities reach a certain size, leading to the termination of bone resorption. The bone degradation process also releases embedded growth factors that reverses bone resorption by recruiting and stimulating the differentiation of mesenchymal stem cells (MSCs) into bone-forming osteoblast lineage cells. Once recruited to the lacunae, preosteoblasts secrete a variety of matrix proteins in the organic bone matrix, or the osteoid, which are then mineralised by mature osteoblasts. Bone formation is terminated upon completion of mineralisation. Osteoblasts either undergo apoptosis or differentiation into quiescent bone lining cells. Alternatively, osteoblasts can become embedded in the bone matrix to form osteocytes, which form a canalicular network of branched dendritic processes to communicate with bone lining cells, osteoblasts, and other osteocytes.