In studies with mice, scientists have found evidence that the cause of osteoporosis-like bone disorders, inflammatory bowel disease, and celiac disease may be an abnormal regulation of a common protein, according to a recent study from the UK.

Osteoporosis is a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, with a consequential increase in bone fragility and susceptibility to fracture.

IBD is a term that refers to two diseases of the intestines: Crohn’s disease (CD) and ulcerative colitis (UC).

Autoimmune-related bone disease and intestinal inflammation are closely linked with the deregulation and the hyper-activation of auto-reactive CD4 T cells, which scientists know are involved in the body’s immune response. It is not known, however, exactly how these cells work.

Mice that were genetically engineered to lack a key regulator of CD4 T cells (Interleukin-2-deficient) have overactive T cells and spontaneously develop UC and the loss of bone cells, the researchers explain. Their experiments indicate that an increased production of a protein called RANKL causes this. The hyperactive CD4 T cells produce too much of this protein, which then contributes to bone breakdown and bowel inflammation.

Treating mice with osteoprotegerin, a protein that prevents RANKL from binding to its receptor, reversed this bone loss, and reduced inflammation in the gut.

This research suggests that some bone diseases and intestinal diseases may share a common cause, and may have significant implications for the treatment of human disease. If similar mechanisms occur in humans, then osteoprotegerin might prove a useful treatment for ulcerative colitis, Crohn’s disease, and celiac disease, which are often accompanied by bone loss.

The researchers conclude, “If therapeutic interventions were available to treat both the osteopenia found in these conditions, alongside reducing the gut inflammation, then both improvements in quality of life and reduction in complications associated with these diseases could be achieved.”

More research is required before we will know whether this is a viable anti-inflammatory treatment for humans.

First published in the Inside Tract® newsletter issue 141 – January/February 2004
A J Ashcroft, S M Cruickshank, P I Croucher, et al. Colonic Dendritic Cells, Intestinal Inflammation, and T Cell-Mediated Bone Destruction Are Modulated by Recombinant Osteoprotegerin. Immunity. 2003;19(6): 849-861.