Intestinal Vitamin D Receptor is Dispensable for Maintaining Adult Bone Mass in Mice with Adequate Calcium Intake.

1,25(OH)2D3-mediated intestinal calcium (Ca) absorption supplies Ca for proper bone mineralization during growth. We tested whether vitamin D receptor (VDR)-mediated 1,25(OH)2D3 signaling is critical for adult Ca absorption and bone by using mice with inducible Vdr gene knockout in the whole intestine (villin-CreERT2+/- x VDRf/f, WIK) or in the large intestine (CDX2-CreERT2+/-x VDRf/f, LIK). At 4-month-old, Vdr alleles were recombined (0.05 mg tamoxifen/g BW, i.p., 5-d) and mice were fed diets with either 0.5% (adequate) or 0.2% (low) Ca. Ca absorption was examined after 2 weeks while serum 1,25(OH)2D3, bone mass, and bone microarchitecture were examined after 16 weeks. Intestinal and renal gene expression was measured at both time points (n = 12/genotype/diet/time point). On the 0.5% Ca diet, all phenotypes in WIK and LIK mice were similar to the controls. Control mice adapted to the 0.2% low Ca diet by increasing renal Cyp27b1 mRNA (3-fold), serum 1,25(OH)2D3 level (1.9-fold), and Ca absorption in the duodenum (Dd,  + 131%) and proximal colon (PCo,  + 28.9%), which prevented bone loss. In WIK mice, low Ca diet increased serum 1,25(OH)2D3 (4.4-fold) but Ca absorption remained unaltered in Dd and PCo. Consequently, significant bone loss occurred in WIK mice (e.g. cortical thickness, Ct.Th, -33.7%). LIK mice adapted to the low Ca diet in the Dd but not the PCo and the impact on bone phenotypes was milder (e.g. Ct.Th, -13.1%). Our data suggest intestinal VDR in adult mice prevents bone loss under low calcium intake but is dispensable under adequate calcium intake.