Advances in the understanding of mineral and bone metabolism in 1 inflammatory bowel diseases

12 Chronic inflammatory disorders such as inflammatory bowel diseases (IBD) affect bone 13 metabolism and are frequently associated with the presence of osteopenia, osteoporosis, and 14 increased risk of fractures. Although several mechanisms may contribute to skeletal 15 abnormalities in IBD patients, inflammation and inflammatory mediators such as tumor necrosis 16 factor (TNF), IL-1β, and IL-6 may be the most critical. It is not clear whether the changes in bone 17 metabolism leading to decreased mineral density are the result of decreased bone formation, 18 increased bone resorption, or both, with varying results reported in experimental models of IBD 19 and in pediatric and adult IBD patients. New data, including our own, challenges the 20 conventional views, and contributes to the unraveling of an increasingly complex network of 21 interactions leading to the inflammation-associated bone loss. Since nutritional interventions 22 (dietary calcium and vitamin D supplementation) are of limited efficacy in IBD patients, 23 understanding the pathophysiology of osteopenia and osteoporosis in Crohn’s disease and 24 ulcerative colitis is critical for the correct choice of available treatments or the development of 25 new targeted therapies. In this review, we discuss current concepts explaining the effects of 26 inflammation, inflammatory mediators and their signaling effectors on calcium and phosphate 27 homeostasis, osteoblast and osteoclast function, and the potential limitations of vitamin D used 28 as an immunomodulator and anabolic hormone in IBD. 29