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

Abstract

Ghishan FK, Kiela PR. Advances in the understanding of mineral and bone metabolism in inflammatory bowel diseases. Am J Physiol Gastrointest Liver Physiol 300: G191-G201, 2011. First published November 18, 2010 doi:10.1152/ajpgi.00496.2010.-Chronic inflammatory disorders such as inflammatory bowel diseases (IBDs) affect bone metabolism and are frequently associated with the presence of osteopenia, osteoporosis, and increased risk of fractures. Although several mechanisms may contribute to skeletal abnormalities in IBD patients, inflammation and inflammatory mediators such as TNF, IL-1␤, and IL-6 may be the most critical. It is not clear whether the changes in bone metabolism leading to decreased mineral density are the result of decreased bone formation, increased bone resorption, or both, with varying results reported in experimental models of IBD and in pediatric and adult IBD patients. New data, including our own, challenge the conventional views, and contributes to the unraveling of an increasingly complex network of interactions leading to the inflammationassociated bone loss. Since nutritional interventions (dietary calcium and vitamin D supplementation) are of limited efficacy in IBD patients, understanding the pathophysiology of osteopenia and osteoporosis in Crohn's disease and ulcerative colitis is critical for the correct choice of available treatments or the development of new targeted therapies. In this review, we discuss current concepts explaining the effects of inflammation, inflammatory mediators and their signaling effectors on calcium and phosphate homeostasis, osteoblast and osteoclast function, and the potential limitations of vitamin D used as an immunomodulator and anabolic hormone in IBD.bone mineral density; Crohn's disease; osteopenia; osteoporosis; ulcerative colitis INFLAMMATORY BOWEL DISEASES (IBDs) represent a group of chronic inflammatory disorders of the intestinal tract that to this date remains idiopathic. More recent basic and clinical research indicates that the chronic inflammatory reaction of the intestinal mucosa is directed against the gut microbiota in individuals with genetic and/or environmental susceptibilities. Disease onset occurs typically during young adulthood (25-35 yr), although ϳ20 -25% of cases are diagnosed during childhood (93). On a clinical basis, two major subtypes of IBD are defined as Crohn's disease (CD), which potentially affects any part of the gastrointestinal tract from the mouth to the anus, and ulcerative colitis (UC), an inflammatory condition limited to the colonic mucosa. However, IBD does not affect just a single organ and should be considered a systemic disease with several extraintestinal manifestations, which occur in a large proportion of IBD patients (60). Osteopenia and osteoporosis are two of the more common extraintestinal symptoms with a general consensus that IBD patients are at a significantly higher risk of developing metabolic bone disease and low bone mineral density (BMD) than the healthy subjects. The relative risk of fractur...

High vitamin D3diet administered during active colitis negatively affects bone metabolism in an adoptive T cell transfer model

“…The effects of vitamin D alone or in combination with bisphosphonates in BMD in IBD patients yielded inconclusive data, with some studies indicating significant benefits (46), limited effects (5), or no effect (6). In light of the increasing complexity of the gut-renal-skeletal axis and the associated regulatory networks, we have postulated that supplementation with a high dose of vitamin D 3 may be detrimental or have a limited beneficial potential to bone health if used during the uncontrolled phase of inflammation in IBD patients, and we have suggested that, in patients at clear risk of osteopenia or osteoporosis or with proven osteopenia or osteoporosis, vitamin D 3 be withheld until remission is achieved (18,19). To test this hypothesis, we used an established and clinically relevant model of adoptive T cell transfer colitis induced under dietary supply of HED of ϳ730 IU/day.…”

Adult Lactose Digestion Status and Effects on Disease

“…(43). On the patient level, the results from different studies do not specifically implicate dairy products (82), although low calcium and low vitamin D are risks for osteopenia (83,84), and associated with increased risk for colorectal cancer (85). There are fewer cohort studies examining the impact of dairy food consumption on IBD.…”

Experimental Colitis Is Associated with Transcriptional Inhibition of Na+/Ca2+ Exchanger Isoform 1 (NCX1) Expression by Interferon γ in the Renal Distal Convoluted Tubules

“…Systemic imbalance of Ca 2ϩ homeostasis, including disturbed renal and intestinal Ca 2ϩ (re)absorption, has been hypothesized to contribute to the pathophysiology of bone loss associated with chronic inflammatory disorders, and especially with inflammatory bowel diseases (IBD) 3 (3,4). Indeed, increased urinary Ca 2ϩ excretion has been described in IBD patients and in mouse models of colitis (5,6).…”