title: Increased osteoclast formation and activity by peripheral blood mononuclear cells in chronic liver disease patients with osteopenia.
abstract: Osteoporosis is a common complication of chronic liver disease, and the underlying mechanisms are not understood. We aimed to determine if osteoclasts develop from osteoclast precursors in peripheral blood mononuclear cells (PBMCs) of chronic liver disease patients with osteopenia compared with controls. PBMCs were isolated and fluorescence-activated cell sorting was performed to quantify the activated T lymphocyte population and receptor activator of nuclear factor kappabeta ligand (RANKL) expression. The activated T lymphocyte populations were comparable for all 3 groups, and RANKL was not detectable. The percentage of CD14+CD11b+ cells containing osteoclast precursors was comparable between the 3 groups. To assess the formation and functional activity of osteoclasts formed from circulating mononuclear cells, PBMCs were cultured (1) without addition of cytokines, (2) with macrophage colony-stimulating factor (M-CSF), (3) with M-CSF and osteoprotegerin, and (4) with M-CSF and RANKL. The number of tartrate-resistant acid phosphatase-positive multinucleated cells and bone resorption was assessed. PBMCs from chronic liver disease patients with osteopenia formed more osteoclast-like cells, which, when cultured in the presence of M-CSF and RANKL resorbed more bone than controls. The number of osteoclast-like cells and the amount of bone resorption correlated with lumbar bone densities. Addition of M-CSF increased numbers of osteoclast-like cells formed in healthy controls; however, this was not observed in either of the chronic liver disease groups. Plasma levels of M-CSF were elevated in both patient groups compared with healthy controls.
  
  
  CONCLUSIONS
  Circulating mononuclear cells from chronic liver disease patients with osteopenia have a higher capacity to become osteoclasts than healthy controls or chronic liver disease patients without osteopenia. This could partially be due to priming with higher levels of M-CSF in the circulation.
authors.affiliation: Hepatology Research Laboratory, Department of Immunology and Internal Medicine, University of Pretoria, South Africa.
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Olivier
authors.forename: Ton
authors.initials: T
authors.lastname: Schoenmaker
authors.forename: Reina E
authors.initials: RE
authors.lastname: Mebius
authors.forename: Vincent
authors.initials: V
authors.lastname: Everts
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Mulder
authors.forename: Karin M J
authors.initials: KM
authors.lastname: van Nieuwkerk
authors.forename: Teun J
authors.initials: TJ
authors.lastname: de Vries
authors.forename: Schalk W
authors.initials: SW
authors.lastname: van der Merwe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001851:Bone Diseases, Metabolic / Q000209:etiology / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D001862:Bone Resorption / Q000503:physiopathology; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002908:Chronic Disease; D005260:Female; D006801:Humans; D008107:Liver Diseases / Q000150:complications / Q000276:immunology* / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010010:Osteoclasts / Q000166:cytology*; D053245:RANK Ligand / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D053245:RANK Ligand; C505688:TNFSF11 protein, human; D016173:Macrophage Colony-Stimulating Factor