title: The influence of serum cytokines and growth factors on osteoclast formation in Paget's disease.
abstract: BACKGROUND
  Osteoclasts are multinucleated cells (MNCs) that form from circulating mononuclear precursors in the presence of the receptor activator of nuclear factor kappa B-ligand (RANKL) and macrophage-colony stimulating factor (M-CSF).
  
  
  OBJECTIVE
  To determine whether cytokines and growth factors influence RANKL/M-CSF induced osteoclastogenesis and bone resorption in Paget's disease.
  
  
  METHODS
  Prospective case-control study.
  
  
  METHODS
  Serum levels of M-CSF, interleukin (IL)-1 beta, IL-6 and tumour necrosis factor-alpha (TNFalpha) were measured in 13 Paget's disease patients and 8 normal controls. The effect of serum from Paget's patients on osteoclast formation was also assessed.
  
  
  RESULTS
  Serum levels of IL-1 beta, IL-6 and TNFalpha were low or undetectable in Paget's disease patients and normal controls. Levels of M-CSF were significantly increased in Paget's patients who were not currently under treatment. In Paget's patients under treatment, serum M-CSF levels were not significantly different from normal controls. The addition of serum from untreated Paget's patients dose-dependently increased RANKL-induced osteoclast formation and lacunar resorption in normal monocyte cultures; elevated IL-6 levels were found in the supernatant and the addition of a specific antibody to human IL-6 blocked the increase in osteoclast formation and resorption. Serum from untreated Paget's patients also induced osteoclast formation in the absence of exogenous M-CSF; an antibody specific to human M-CSF abolished this effect.
  
  
  CONCLUSIONS
  Both M-CSF and IL-6 play a major role in osteoclast formation and bone resorption in Paget's disease and measurement of serum M-CSF may provide a useful indicator of disease activity.
authors.affiliation: Nuffield Department of Orthopaedic Surgery, University of Oxford, UK.
authors.forename: S D
authors.initials: SD
authors.lastname: Neale
authors.forename: E
authors.initials: E
authors.lastname: Schulze
authors.forename: R
authors.initials: R
authors.lastname: Smith
authors.forename: N A
authors.initials: NA
authors.lastname: Athanasou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D006133:Growth Substances / Q000097:blood*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000502:physiology; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010001:Osteitis Deformans / Q000097:blood / Q000473:pathology*; D010010:Osteoclasts / Q000473:pathology*; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D015415:Biomarkers; D016207:Cytokines; D006133:Growth Substances; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor