Cellular and humoral mechanisms of osteoclast formation and bone resorption in Gorham-Stout disease

Gorham-Stout disease (GSD) is a rare, massively osteolytic condition which is associated with increased vascularity and an increase in osteoclast numb ers. To determine the cellular and Immoral mechanisms underlying the increa se in osteoclast numbers and osteolysis in GSD, this study analysed circula ting osteoclast precursor numbers and sensitivity to osteoclastogenic facto rs in a GSD patient and age/sex-matched controls. Monocytes were cultured w ith NI-CSF (25 ng/ml) and RANKL (30 ng/ml) and osteoclast formation was ass essed in terms of the formation of TRAP(+) and VNR+ multinucleated cells an d the extent of lacunar resorption. There was no increase in the proportion of circulating osteoclast precursors in GSD relative to controls, but lacu nar resorption was consistently greater in GSD monocyte cultures. Increased osteoclast formation in GSD was noted when monocytes were incubated with I L-1 beta (I m/ml), IL-6/sIL-6R (100 ng/ml), and TNF alpha (10 ng/ml). An in crease in osteoclast differentiation and bone resorption was also noted in control monocyte cultures in the presence of GSD serum. These results indic ate that the increase in osteoclast formation in GSD is due not to an incre ase in the number of circulating osteoclast precursors, but rather to an in crease in the sensitivity of these precursors to Immoral factors which prom ote osteoclast formation and bone resorption. Copyright (C) 2001 John Wiley & Sons, Ltd.