The role of the laboratory in investigation and management of bone disease

摘要

The phrase "dry as a bone" may refer to dead bone, but the living bone is neither dry nor inert. Even after growth is completed, the adult bone is continuously being remodelled and renewed.Regulation of bone remodelling:Our understanding of the cellular/molecular mechanisms that modulate normal bone growth and bone remodelling as well as bone pathology has undergone major advances in recent times, as Kular et al. describe in this special issue on bone and calcium. The unfolding knowledge of bone physiology and pathology has led to progress not only in diagnosing bone disease, making treatment decisions and monitoring, but also in identifying potential new molecular targets for treating bone disease, which has led to the emergence of new and novel therapies. The Wnt/ [S-catenin signalling pathway is important in regulating osteoblastic bone formation; physiological inhibitors of this pathway include sclerostin and Dickkopf (DKK-1). Monoclonal antibodies to sclerostin and DKK-1 are being studied in clinical trials for the treatment of osteoporosis and multiple myeloma respectively, and show great promise as anabolic agents which not only increase bone formation, but also decrease bone resorption at the same time. Another target for therapy is the enzyme cathepsin K (CatK), produced by osteoclasts, which mediates the degradation of bone matrix. Preclinical studies have demonstrated that inhibition of CatK leads to a decrease in bone resorption. Clinical studies of CatK inhibitors in osteoporosis and cancer-induced bone disease suggest that unlike currently available antiresorptive agents such as bisphosphonates and denosumab [receptor activator of nuclear factor-KB (RANK) ligand antibody] which suppress bone resorption with subsequent reduction of bone formation due to coupling, CatK inhibitors suppress bone resorption without affecting bone formation, resulting in progressive increases in bone density.