Osteoclast formation and activity in the pathogenesis of osteoporosis in rheumatoid arthritis.
OBJECTIVE
Rheumatoid arthritis (RA) is often complicated by generalized osteopenia due to increased bone resorption by osteoclasts. We analysed a number of cellular and humoral factors that influence osteoclast formation from circulating precursors in RA patients.


METHODS
Monocytes isolated from RA patients and normal controls were cultured with macrophage colony-stimulating factor (M-CSF) and nuclear factor-kappaB ligand (RANKL), or with RANKL-expressing UMR106 cells and 1,25 dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. Osteoclast differentiation was assessed by expression of tartrate-resistant acid phosphatase (TRAP) and vitronectin receptors (VNR) and lacunar resorption.


RESULTS
Osteoclasts formed from RA patients exhibited increased resorptive activity but there was no difference in the relative proportion of circulating osteoclast precursors between RA patients and normal controls. Osteoclast precursors in RA patients were not more sensitive to the osteoclastogenic effects of 1,25(OH)(2)D(3), M-CSF or RANKL. Dexamethasone, but not interleukin (IL) 1beta, tumour necrosis factor alpha and IL-6, increased osteoclast formation and lacunar resorption.


CONCLUSIONS
There is an increase in the extent of lacunar resorption carried out by osteoclasts formed from circulating precursors in RA patients. This is not due to an increase in the number of circulating precursors or increased sensitivity to the osteoclastogenic effects of 1,25(OH)(2)D(3), M-CSF, RANKL or inflammatory cytokines. Our findings suggest that increased osteoclast functional activity rather than osteoclast formation is more likely to play a role in the generalized bone loss that occurs in RA, and that corticosteroids stimulate osteoclast formation and resorption.
Hirayama
T
T
Nuffield Department of Orthopaedic Surgery, University of Oxford, Nuffield Orthopaedic Centre, Oxford OX3 7LD, UK.
Danks
L
L
Sabokbar
A
A
Athanasou
N A
NA
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000473:pathology; D001862:Bone Resorption / Q000503:physiopathology; D002352:Carrier Proteins / Q000494:pharmacology*; D016022:Case-Control Studies; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology; D017077:Culture Media, Conditioned; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D008875:Middle Aged; D009000:Monocytes; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology*; D010024:Osteoporosis / Q000209:etiology / Q000473:pathology; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D012016:Reference Values; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D007375:Interleukin-1; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D014409:Tumor Necrosis Factor-alpha; D002762:Cholecalciferol; D003907:Dexamethasone; D016173:Macrophage Colony-Stimulating Factor