High vitamin D^sub 3^ diet administered during active colitis negatively affects bone metabolism in an adoptive T cell transfer model

Decreased bone mineral density (BMD) represents an extraintestinal complication of inflammatory bowel disease (IBD). Vitamin D... has been considered a viable adjunctive therapy in IBD. However, vitamin D... plays a pleiotropic role in bone modeling and regulates the bone formation-resorption balance, depending on the physiological environment, and supplementation during active IBD may have unintended consequences. We evaluated the effects of vitamin D... supplementation during the active phase of disease on colonic inflammation, BMD, and bone metabolism in an adoptive IL-10... CD4+ T cell transfer model of chronic colitis. High-dose vitamin D... supplementation for 12 days during established disease had negligible effects on mucosal inflammation. Plasma vitamin D... metabolites correlated with diet, but not disease, status. Colitis significantly reduced BMD. High-dose vitamin D... supplementation did not affect cortical bone but led to a further deterioration of trabecular bone morphology. In mice fed a high vitamin D... diet, colitis more severely impacted bone formation markers (osteocalcin and bone alkaline phosphatase) and increased bone resorption markers, ratio of receptor activator of NF-KB ligand to osteoprotegrin transcript, plasma osteoprotegrin level, and the osteoclast activation marker tartrate-resistant acid phosphatase (ACp5). Bone vitamin D receptor expression was increased in mice with chronic colitis, especially in the high vitamin D... group. Our data suggest that vitamin D..., at a dose that does not improve inflammation, has no beneficial effects on bone metabolism and density during active colitis or may adversely affect BMD and bone turnover. These observations should be taken into consideration in the planning of further clinical studies with high-dose vitamin D... supplementation in patients with active IBD. (ProQuest: ... denotes formulae/symbols omitted.)