Bone in Health and DiseaseBone Physiology and Osteoporosis

Published January 2015 Updated October 2016 13 lectures
Prof. Juliet Compston
University of Cambridge, Cambridge, UK
Summary

In recent years there have been major advances in our understanding of bone physiology, many of which have been translated into the diagnosis and management of bone disease. Bone remodeling, which is a key process in maintaining the mechanical integrity of the skeleton, involves resorption by osteoclasts followed by bone... read moreformation by osteoblasts. In the past decade new pathways regulating bone remodeling have been characterized. In particular, the RANK ligand/RANK/OPG pathway has emerged as central to the control of osteoclast development and activity and has been exploited in the development of a new treatment for osteoporosis in the form of an antibody to RANKL. Characterisation of the Wnt signaling pathway in the control of bone formation, with its involvement of the co-receptors LRP5 and 6 and inhibitors sclerostin and Dickoff proteins has significantly enhanced our understanding of how bone formation is regulated and has also produced new therapeutic targets for the treatment of osteoporosis. Recent studies on osteocytes, cells that are buried within bone and have extensive communicating networks with each other and cells on the bone surface, have produced exciting new information about their role not only as mechanosensors but also as regulators of osteoclast and osteoblast activity.

Age-related bone loss is a universal phenomenon affecting both men and women, starting during the fifth decade and continuing thereafter throughout life. Structural decay resulting from the changes in bone remodeling during ageing occurs in both cortical and trabecular bone and leads to the increased bone fragility that characterizes osteoporosis. Advances in imaging have enabled more precise characterization of these structural changes, particularly in cortical bone, in untreated and treated bone disease and have shown intriguing differences in how different interventions affect cortical and trabecular bone.

Osteoporosis is widely recognised as a major health problem in elderly populations throughout the world, causing significant morbidity and mortality and resulting in huge economic costs to health care services. The ability accurately to predict fracture risk is key to the appropriate targeting of treatment, and fracture risk algorithms such as FRAX are now routinely incorporated into clinical practice. A range of therapeutic options to reduce fracture risk has also become available over the past two decades which, when appropriately targeted, are highly cost-effective. Several new approaches are also currently being developed, including anti-sclerostin antibodies and inhibitors of cathepsin K. Currently unresolved issues in the management of osteoporosis include the optimal duration of therapy, use of combination therapy, and the role of calcium and vitamin D supplementation.