Inflammatory Bowel Disease: Effects on Bone and Mechanisms.

ABSTRACT

Inflammatory bowel disease (IBD) is associated with decreased bone mass and alterations in bone geometry from the time of diagnosis, before anti-inflammatory therapy is instituted. Deficits in bone mass can persist despite absence of symptoms of active IBD. The effects of IBD on the skeleton are complex. Protein-calorie malnutrition, inactivity, hypogonadism, deficits in calcium intake and vitamin D consumption and synthesis, stunted growth in children, decreased skeletal muscle mass, and inflammation all likely play a role. Preliminary studies suggest that the dysbiotic intestinal microbial flora present in IBD may also affect bone at a distance. Several mechanisms are possible. T cells activated by the gut microbiota may serve as "inflammatory shuttles" between the intestine and bone. Microbe-associated molecular patterns leaked into the circulation in IBD may activate immune responses in the bone marrow by immune cells and by osteocytes, osteoblasts, and osteoclasts that lead to decreased bone formation and increased resorption. Finally, intestinal microbial metabolites such as H2S may also affect bone cell function. Uncovering these mechanisms will enable the design of microbial cocktails to help restore bone mass in patients with IBD.