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OBJECTIVE: An imbalance between bone formation and bone resorption is thought to underlie the pathogenesis of reduced bone mass in osteoporosis. Bone resorption is carried out by osteoclasts. which are formed from marrow-derived cells that circulate in the monocyte fraction. The aim of this study was to determine the role of osteoclast formation in the pathogenesis of bone loss in osteoporosis. METHODS: The proportion of circulating osteoclast precursors and their relative sensitivity to the osteoclastogenic effects of M-CSF. 1,25(OH)2D3 and RANKL were assessed in primary osteoporosis patients and normal controls. RESULTS: Although there was no difference in the number of circulating osteoclast precursors in osteoporosis patients and normal controls. osteoclasts formed from osteoporosis patients exhibited substantially increased resorptive activity relative to normal controls. Although no increased sensitivity to the osteoclastogenic effects of 1,25(OH)D3 or M-CSF was noted, increased bone resorption was found in osteoporosis peripheral blood mononuclear cell (PBMC) cultures to which these factors were added. CONCLUSION: Our findings suggest that osteoclast functional activity rather than formation is increased in primary involutional osteoporosis and that dexamethasone acts to increase osteoclast formation.

Original publication

DOI

10.1080/03009740310000102

Type

Journal article

Journal

Scandinavian journal of rheumatology

Publication Date

01/2003

Volume

32

Pages

95 - 100

Addresses

Nuffield Department of Orthopaedic Surgery, University of Oxford, Nuffield Orthopaedic Centre, Oxford, UK.

Keywords

Leukocytes, Mononuclear, Cells, Cultured, Osteoclasts, Stem Cells, Humans, Osteoporosis, Bone Resorption, Calcitriol, Dexamethasone, Carrier Proteins, Macrophage Colony-Stimulating Factor, Membrane Glycoproteins, Biological Markers, Immunoenzyme Techniques, Coculture Techniques, Dose-Response Relationship, Drug, Aged, Middle Aged, Female, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B