The osteoclast, bone remodelling and treatment of metabolic bone disease

Eur J Clin Invest. 2012 Dec;42(12):1332-41. doi: 10.1111/j.1365-2362.2012.02717.x. Epub 2012 Sep 23.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Bone Density Conservation Agents / pharmacology*
  • Bone Diseases, Metabolic / drug therapy*
  • Bone Remodeling / drug effects*
  • Bone Remodeling / physiology
  • Bone Resorption / metabolism*
  • Drug Design
  • Humans
  • Macrophage Colony-Stimulating Factor / metabolism
  • Osteoblasts / metabolism
  • Osteoclasts / metabolism*
  • RANK Ligand / metabolism

Substances

  • Bone Density Conservation Agents
  • RANK Ligand
  • Macrophage Colony-Stimulating Factor