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

Abstract

Gorham-Stout disease (GSD) is a rare, massively osteolytic condition which is associated with increased vascularity and an increase in osteoclast numbers. To determine the cellular and humoral mechanisms underlying the increase in osteoclast numbers and osteolysis in GSD, this study analysed circulating osteoclast precursor numbers and sensitivity to osteoclastogenic factors in a GSD patient and age/sex-matched controls. Monocytes were cultured with M-CSF (25 ng/ml) and RANKL (30 ng/ml) and osteoclast formation was assessed in terms of the formation of TRAP(+) and VNR(+) multinucleated cells and the extent of lacunar resorption. There was no increase in the proportion of circulating osteoclast precursors in GSD relative to controls, but lacunar resorption was consistently greater in GSD monocyte cultures. Increased osteoclast formation in GSD was noted when monocytes were incubated with IL-1beta (1 ng/ml), IL-6/sIL-6R (100 ng/ml), and TNFalpha (10 ng/ml). An increase in osteoclast differentiation and bone resorption was also noted in control monocyte cultures in the presence of GSD serum. These results indicate that the increase in osteoclast formation in GSD is due not to an increase in the number of circulating osteoclast precursors, but rather to an increase in the sensitivity of these precursors to humoral factors which promote osteoclast formation and bone resorption.

Gorham-Stout syndrome in mainland China: a case series of 67 patients and review of the literature

“…In our case series, the osteoclast in areas of bone resorption was found in only five cases (7.5%), which suggested "osteoclastosis" may be not necessary in this entity. Some authors described that interleukin-6 (IL-6) may cause bone resorption because it can stimulate osteoclast activity and increase sensitivity of osteoclast precursors to humoral factors (Möller et al, 1999;Hirayama et al, 2001;Hammer et al, 2005). Devlin et al (1996) demonstrated that the blood level of IL-6 was seven times the upper limit of the normal range, and fell to one quarter the pretreatment value after further treatment.…”

Gorham's Disease or Massive Osteolysis

“…Hirayama and colleagues 130 have reported on the cellular and humoral mechanisms of osteoclast formation and bone resorption in patients with Gorham-Stout syndrome. These authors suggested that the increase in osteoclast formation in Gorham-Stout syndrome is not due to an increase in the number of circulating osteoclast precursors, but rather to an increase in the sensitivity of these precursors to humoral factors which promote osteoclast formation and bone resorption.…”

A Rare Variant of Angiogenic Vertebral Body Destruction in a Child: Gorham’s Disease?

“…Мнения о роли остеокластов в деструкции костной ткани при GSD противоречивы: ряд исследователей подтверждает их высокую активность [1,5,6,18,22,26,32,36,42,44,48,50], другие отмечают их отсутствие в оча-гах остеолиза [12,13,21,45,51]. При-чина такого противоречия, возмож-но, обусловлена проведением гисто-логического исследования на разных стадиях процесса [4].…”