Osteoclast formation from circulating precursors in osteoporosis.
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.


CONCLUSIONS
Our findings suggest that osteoclast functional activity rather than formation is increased in primary involutional osteoporosis and that dexamethasone acts to increase osteoclast formation.
Nuffield Department of Orthopaedic Surgery, University of Oxford, Nuffield Orthopaedic Centre, Oxford, UK.
M
M
Jevon
T
T
Hirayama
M A
MA
Brown
J A H
JA
Wass
A
A
Sabokbar
S
S
Ostelere
N A
NA
Athenasou
D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001862:Bone Resorption / Q000139:chemically induced / Q000503:physiopathology*; D002117:Calcitriol / Q000494:pharmacology; D002352:Carrier Proteins / Q000494:pharmacology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000494:pharmacology; D008875:Middle Aged; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D010024:Osteoporosis / Q000209:etiology* / Q000473:pathology; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D013234:Stem Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology*
D015415:Biomarkers; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D003907:Dexamethasone; D016173:Macrophage Colony-Stimulating Factor; D002117:Calcitriol