Q J Med 2002; 95: 233-240
© 2002 Association of Physicians
The influence of serum cytokines and growth factors on osteoclast formation in Paget's disease
1 From the Nuffield Department of Orthopaedic Surgery, University of Oxford, and 2 Department of Pathology, Nuffield Orthopaedic Centre, Oxford, UK
Received 1 November 2001 and in revised form 24 January 2002
Background: Osteoclasts are multinucleated cells (MNCs) that form from circulating mononuclear precursors in the presence of the receptor activator of nuclear factor 
B-ligand (RANKL) and macrophage-colony stimulating factor (M-CSF).
Aim: To determine whether cytokines and growth factors influence RANKL/M-CSF induced osteoclastogenesis and bone resorption in Paget's disease.
Design: Prospective case-control study.
Methods: Serum levels of M-CSF, interleukin (IL)-1ß, IL-6 and tumour necrosis factor-
(TNF) 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-1ß, IL-6 and TNF 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.
Discussion: 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.
Address correspondence to Dr N.A. Athanasou, Department of Pathology, Nuffield Orthopaedic Centre, Windmill Road, Headington, Oxford OX3 7LD. nick.athanasou{at}ndos.ox.ac.uk
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