Bone Remodeling: Clinical Evaluation

The term bone remodeling indicates a series of physiological processes that involve three types of cells, osteoclasts, osteoblasts, and osteocytes, and are regulated by complex interactions of numerous cytokines engaged in different patways. Together with local factors, bone remodeling is also regulated by hormones such as estrogens, androgens, parathyroid hormone, calcitonin, growth hormone, glucocoticoids. Bone remodeling is organized in five stages, called activation, resorption, reversal, formation, and termination; and it occurs in specific anatomical structures known as basic multicellular units (BMUs). Within these spaces, bone resorption and formation are coupled during the maturity, and the amount of removed bone is balanced by the newly formed one; with ageing the mechanism becomes progressively uncoupled, with an inadequate bone formation phase. Different phases of bone remodeling are regulated by specific mechanisms: the main signaling systems are RANKL/RANK/OPG, Wnt/beta-catenin pathway, sclerostin, and Dickkopf-related protein 1 (DKK1). Other coupling factors include transforming growth factor (TGF)-β, platelet derived growth factor (PDGF), insulin-like growth factor (IGF)-1, vascular endothelial growth factor (VEGF), cathepsin K, semaphorins (SEMAs), bone morphogenetic proteins (BMPs). Many skeletal disorders are strictly related to pathological modifications of bone remodeling, due to perturbations in specific pathways. In osteoporosis bone loss is strictly related to enhanced bone resorption, as well as sclerosing bone desorders result from unbalanced formation phase. In osteomalacia, due to vitamin D insufficiency and/or hypophosphatemia, the presence of osteoid surface indicates inadequate mechanisms of bone mineralization, with usually increased bone resorption due to secondary hyperparathyroidism. Paget’s disease of bone is a localized bone disorder in which enhanced bone resorption is related to the presence of abnormal osteoclasts increased in size and number: in the mixed phase of the disease, the accelerated bone resorption is coupled with an increased new bone formation.