Bone Disease and Intestinal Problems May Share a Common Cause
01/07/04 11:47 AM
By Megan Rauscher
NEW YORK (Reuters Health) Dec 26 - Scientists have evidence in mice that osteoporosis-like bone disorders and inflammatory intestinal disorders are both caused by abnormal regulation of a common protein.
Dr. Simon R. Carding from the University of Leeds in England and colleagues report their study in the December issue of the journal Immunity. "Autoimmune associated bone disease and intestinal inflammation are closely linked with deregulation and hyperactivation of autoreactive CD4 T cells," they write. "How these T cells are activated and mediate disease is not clear."
Mice engineered to lack a key regulator of CD4 T cells have overactive T cells and spontaneously develop ulcerative colitis and osteopenia, the scientists explain. Dr. Carding and colleagues' experiments indicate that this is caused by increased production of the ligand for receptor activator of NFkB (RANKL).
"We find that the hyperactive CD4 T cells produce too much of this protein, which then contributes to bone breakdown and bowel inflammation," Dr. Carding said.
Treating mice with exogenous recombinant osteoprotegerin -- a protein that interferes with RANKLs binding to its receptor -- reversed bone loss and improved colitis.
"This study shows that some bone diseases and intestinal problems may share a common cause," Dr. Carding told Reuters Health. "If similar mechanisms occur in humans, then osteoprotegerin might prove a useful treatment for intestinal disorders such as ulcerative colitis and Crohn's disease," he said, which are both often accompanied by bone loss.