alexa Interleukin-6: a potential mediator of the massive osteolysis in patients with Gorham-Stout disease.


Cosmetology & Oro Facial Surgery

Author(s): Devlin RD, Bone HG rd, Roodman GD

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Abstract Gorham-Stout disease (GSD) or massive osteolysis, is an extremely rare osteolytic condition that involves extensive locally aggressive resorption of bone. The etiology and pathophysiology are unknown, and the role of the osteoclast in GSD is unclear. We studied a patient with GSD who had massive resorption of his mandible, which extended to his maxilla, zygoma, right parietal region, and cranium. To investigate the cause of the extensive resorption, we tested the effects of the patient's serum, sampled early in the course of treatment and later after the osteolysis was stabilized, on the formation of osteoclast-like multinucleated cells (MNC) in cultures of normal human marrow. GSD serum (10\%, vol/vol) markedly increased the number of MNC formed in these cultures compared to that in normal serum as well as stimulated the formation of resorption pits by these MNC on dentine slices. GSD serum, collected after further therapy, did not enhance the number of MNC formed in marrow cultures compared to that in normal serum. Elevated levels of interleukin-6 (IL-6) were detected in the earlier GSD serum that were 7 times the upper limit of the normal range, and after further treatment, IL-6 levels fell to one quarter the pretreatment value. The levels of IL-1 beta, tumor necrosis factor-alpha, transforming growth factor-alpha, PTH, and PTH-related peptide in pretreatment GSD serum were not increased. Moreover, the addition of neutralizing antibodies to IL-6 to the normal human bone marrow cultures effectively blocked the increase in MNC formation induced by active GSD serum. These data suggest that bone resorption in GSD patients is due to enhanced osteoclast activity, and that IL-6 may play a role in the increased bone resorption in GSD. This article was published in J Clin Endocrinol Metab and referenced in Cosmetology & Oro Facial Surgery

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