Gorham and Stout found that vascular anomalies always occupied space that normally would be filled with new bone and speculated that the presence of angiomatosis may lead to chemical changes in the bone. Gorham and others speculated that such a change in the bone chemistry might cause an imbalance in the rate of osteoclast to osteoblast activity such that more bone is dissolved than is replaced. Beginning in the 1990s, elevated levels of a protein called interleukin-6 (IL-6) being detected in people with the disease were reported, leading some to suggest that increased levels of IL-6 and vascular endothelial growth factor (VEGF) may contribute to the chemical changes Gorham and others believed were the cause of this type of osteolysis.