Dissecting the mechanisms of bone loss in Gorham-Stout disease

Michela Rossi; Paola Sabrina Buonuomo; Giulia Battafarano; Antonella Conforti; Eda Mariani; Mattia Algeri; Simone Pelle; Matteo D'Agostini; Marina Macchiaiolo; Rita De Vito; Michaela Veronika Gonfiantini; Alessandro Jenkner; Ippolita Rana; Andrea Bartuli; Andrea Del Fattore

doi:10.1016/j.bone.2019.115068

Dissecting the mechanisms of bone loss in Gorham-Stout disease

Bone. 2020 Jan:130:115068. doi: 10.1016/j.bone.2019.115068. Epub 2019 Sep 13.

Authors

Affiliations

¹ Bone Physiopathology Group, Multifactorial Disease and Complex Phenotype Research Area, Bambino Gesù Children's Hospital, Rome, Italy.
² Rare Diseases and Medical Genetic Unit, Bambino Gesù Children's Hospital, Rome, Italy.
³ Department of Pediatric Hematology and Oncology, Bambino Gesù Children's Hospital, Rome, Italy.
⁴ Research Laboratories, Bambino Gesù Children's Hospital, Rome, Italy.
⁵ Villa Aurora" Clinic, Rome, Italy.
⁶ Clinical Laboratory, Bambino Gesù Children's Hospital, Rome, Italy.
⁷ Histopathology, Bambino Gesù Children's Hospital, Rome, Italy.
⁸ Division of Immunology and Infectious Diseases Department of Pediatrics, Bambino Gesù Children Hospital, Rome, Italy.
⁹ Bone Physiopathology Group, Multifactorial Disease and Complex Phenotype Research Area, Bambino Gesù Children's Hospital, Rome, Italy. Electronic address: andrea.delfattore@opbg.net.

PMID: 31525474
DOI: 10.1016/j.bone.2019.115068

Abstract

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.

Keywords: Bone histomorphometry; Gorham-Stout disease; Osteoblast; Osteoclast; Osteolysis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bone and Bones
Endothelial Cells
Humans
Osteoclasts
Osteolysis*
Osteolysis, Essential*