Colorectal cancer is the third most common cancer in the world. Patients with low vitamin D status have a higher risk of colorectal cancer. The pleiotropic hormone calcitriol (1,25-dihydroxyvitamin D3, 1,25-D3) is the most active vitamin D metabolite. In addition to regulating calcium homeostasis and bone health, calcitriol has anti-proliferative, anti-angiogenic, and pro-apoptotic functions. Both, calcitriol and its precursor calcidiol (25-hydroxyvitamin D3) are catabolized by CYP24A1 (1,25dihydroxyvitamin D3-24-hydroxylase). This enzyme is significantly overexpressed in colorectal tumors compared with the adjacent mucosa. We hypothesized that this overexpression will limit local tissue exposure to calcitriol and thereby reduce its anti-tumorigenic functions and result in highly proliferative tumors. To assess the proliferative potential of the tumors, we measured mRNA expression of several genes responsible for the initiation of DNA replication, including cell division cycle 6 homolog (CDC6) and proliferation markers belonging to the minichromosome maintenance complex (MCM2, MCM4, MCM7) by quantitative real-time PCR (N=57). All proliferation markers were expressed significantly higher in the colorectal tumors compared with the adjacent mucosa. The expression of CYP24A1 correlated with CDC6 (Spearman's Correlation Coefficient, SCC 0.266, pb0.02), MCM2 (SCC 0.341, pb0.009), and MCM7 (SCC 0.290, pb0.029). In a subgroup of patients that show amplification of the CYP24A1 gene locus (more than 6 copies), this correlation became significantly stronger. Our data show that high expression of the vitamin D degrading CYP24A1 correlates with increased proliferation. This might be due to the restricted availability of the antiproliferative calcitriol caused by rapid degradation. doi:10.1016/j.bone.2012.08.005 O05 High dietary vitamin D can prevent chemically-induced colorectal tumorigenesis in mice D.M. Hummel, U. Thiem, I.Sh. Fetahu, J. Hobaus, L. Gober, N. Hacker, J. Graca, I. Mesteri, E. Kallay Department of Pathophysiology and Allergy Research, Medical University of Vienna, Austria Astra Zeneca, Macclesfield, UK Clinical Institute for Pathology, Medical University of Vienna, Austria Division of Endocrinology and Metabolism, Medical University of Graz,