The osteoclast, bone remodelling and treatment of metabolic bone disease
Version of Record online: 23 SEP 2012
© 2012 The Authors. European Journal of Clinical Investigation © 2012 Stichting European Society for Clinical Investigation Journal Foundation
European Journal of Clinical Investigation
Volume 42, Issue 12, pages 1332–1341, December 2012
How to Cite
Boyce, B. F., Rosenberg, E., de Papp, A. E. and Duong, L. T. (2012), The osteoclast, bone remodelling and treatment of metabolic bone disease. European Journal of Clinical Investigation, 42: 1332–1341. doi: 10.1111/j.1365-2362.2012.02717.x
- Issue online: 20 NOV 2012
- Version of Record online: 23 SEP 2012
- Accepted manuscript online: 14 AUG 2012 10:35AM EST
- Received 22 June 2012; accepted 29 July 2012
- Bone formation;
- bone remodelling;
- bone resorption;
Eur J Clin Invest 2012; 42 (12): 1332–1341
Background Bone remodelling maintains skeletal integrity by osteoclasts removing foci of damaged bone and osteoblasts replacing them with new bone. Diseases associated with increased bone resorption have increased remodelling often with inadequate bone formation and increased risk of fracture. New therapies are needed for these diseases to reduce resorption and increase formation.
Design The molecular mechanisms regulating osteoclast and osteoblast functions have become better understood in the past 20 years and have led to questioning of the long-held notion that osteoblastic cells have the dominant regulatory role over osteoclastic cells in bone remodelling. Here, we review current knowledge of how osteoclast formation and functions are regulated and describe how enhanced understanding of these has led to development of new drugs for the management of common bone diseases characterized by increased bone resorption.
Results Osteoclast formation and functions are regulated by cytokines, especially receptor activator of NF-κB ligand (RANKL) and macrophage-colony-stimulating factor (M-CSF). The differentiation, activity and lifecycle of osteoclasts are regulated in part by other cells that reside within the bone. These include osteoblasts, osteocytes and immune cells, which express these cytokines in response to most factors that promote bone resorption. RANKL and M-CSF activate numerous signalling pathways, which are potential targets for therapeutic intervention. Importantly, osteoclastic cells also function as positive and negative regulators of osteoblastic bone formation.
Conclusions There are multiple targets within osteoclasts for pharmacologic intervention to prevent bone loss in osteoporosis and other resorptive bone diseases. However, novel therapies could also affect osteoblastic cell functions.