Dissecting the mechanisms of bone loss in Gorham-Stout disease

•Bone biopsy analysis of Gorham-Stout patients revealed increased vessels, osteoclast number and osteocyte lacunar area.•In vitro experiments displayed increased osteoclast differentiation/activity and reduced osteoblast function.•Patients’ sera stimulated osteoclastogenesis, bone resorption and reduced mineralization of control cells.•The treatment of endothelial cell line EA.hy926 with patients’ sera enhanced vessel formation. Gorham-Stout disease (GSD) is a rare disorder characterized by progressive osteolysis and angiomatous proliferation. Since the mechanisms leading to bone loss in GSD are not completely understood, we performed histological, serum, cellular and molecular analyses of 7 patients. Increased vessels, osteoclast number and osteocyte lacunar area were revealed in patients’ bone biopsies. Biochemical analysis of sera showed high levels of ICTP, Sclerostin, VEGF-A and IL-6. In vitro experiments revealed increased osteoclast differentiation and activity, and impaired mineralization ability of osteoblasts. To evaluate the involvement of systemic factors in GSD, control cells were treated with patients’ sera and displayed an increase of osteoclastogenesis, bone resorption activity and a reduction of osteoblast function. Interestingly, GSD sera stimulated the vessel formation by endothelial cells EA.hy926. These results suggest that bone cell autonomous alterations with the cooperation of systemic factors are involved in massive bone loss and angiomatous proliferation observed in GSD patients.