Dietary Calcium and Phosphorus Ratio Regulates Bone Mineralization and Turnover in Vitamin D Receptor Knockout Mice by Affecting Intestinal Calcium and Phosphorus Absorption

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Abstract
The effects of the dietary Ca and P ratio, independent of any vitamin D effects, on bone mineralization and turnover was examined in 60 VDRKO mice fed different Ca/P ratio diets. High dietary Ca/P ratio promoted bone mineralization and turnover with adequate intestinal Ca and P transports in VDRKO mice. Introduction: To clarify the effects of the dietary calcium (Ca) and phosphorus (P) ratio (Ca/P ratio) on bone mineralization and turnover in null-vitamin D signal condition, vitamin D receptor knockout (VDRKO) mice were given diets containing different Ca/P ratios. Materials and Methods: Five groups of 4-week-old VDRKO mice, 10 animals each, were fed diets for 4 weeks. Group 1 was wild-type littermate mice, fed the diet containing 0.5% Ca and P (Ca/P = 1). Group 2 was the control and was fed a similar diet (Ca/P = 1). Groups 3, 4, 5, and 6 were fed the following diets:0.5% Ca and 1.0% P (Ca/P = 0.5), 1.0% Ca and 1.0% P (Ca/P = 1), 1.0% Ca and 0.5% P (Ca/P = 2), and 0.5% Ca and 0.25% P (Ca/P = 2). Results and Conclusions: Compared with group 2, serum calcium and phosphorus levels in groups 4–6 significantly increased. Serum parathyroid hormone levels increased in group 3 and decreased in group 5. The amounts of intestinal calcium absorption decreased in groups 3 and 4. Phosphorus absorption increased in group 3 and decreased in groups 4–6. Bone mineral content (BMC) and bone mineral density (BMD) of the femur in group 3 significantly decreased and increased in group 5. In the primary spongiosa of the proximal tibia, the trabecular bone volume (BV/TV) and osteoid thickness (O.Th) in group 3 significantly increased, and decreased in group 6. In groups 5 and 6, the numbers of the trabecular osteoclasts increased. In groups 2 and 4, and the secondary spongiosa was identified in 5 of 10 mice. In group 3, there was no secondary spongiosa in either mouse. Osteoid maturation time (OMT) significantly decreased, and bone formation rate (BFR/BS) increased in groups 4–6. These data indicate that the dietary Ca/P ratio regulates bone mineralization and turnover by affecting the intestinal calcium and phosphorus transports in VDRKO mice. They may suggest the existence of Ca/P ratio-dependent, vitamin D-independent calcium and phosphorus transport system in the intestine.

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