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 ϭ 1). Group 2 was the control and was fed a similar diet (Ca/P ϭ 1). Groups 3, 4, 5, and 6 were fed the following diets:0.5% Ca and 1.0% P (Ca/P ϭ 0.5), 1.0% Ca and 1.0% P (Ca/P ϭ 1), 1.0% Ca and 0.5% P (Ca/P ϭ 2), and 0.5% Ca and 0.25% P (Ca/P ϭ 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.

We investigated the hypoglycemic and hypolipidemic effects of two hesperertin glycosides, namely, hesperidin and cyclodextrin (CD)-clathrated hesperetin, in Goto-Kakizaki (GK) weanling rats with type 2 diabetes. We demonstrated that hesperidin and CD-hesperetin normalized glucose metabolism by altering the activities of glucose-regulating enzymes and reducing the levels of lipids in the serum and liver of the GK rats. These effects of hesperidin glycosides were partly produced by altering the expression of genes encoding the peroxisome proliferator-activated receptors, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, and the low-density lipoprotein receptor.

Deficiency of vitamin D, which is required for calcium homeostasis, causes rickets with hypocalcemia and hypophosphatemia, resulting in growth retardation and impaired bone formation. Mice lacking the vitamin D receptor (VDR) develop the typical features of rickets, establishing that VDR plays a role in controlling the actions of vitamin D. Normalization of impaired mineral homeostasis in VDR KO mice fed a diet supplemented with high concentrations of calcium (2%) and phosphorus (1.25%) is reported to reverse the malformation of bone and the growth retardation as well. However, the relationship between mobilization of phosphorus and calcium and nuclear control of vitamin D actions remains unclear. The present study was undertaken to determine the effect of dietary phosphorus on mineral mobilization and bone mineralization. We report here that feeding a diet supplemented with a restricted amount of phosphorus (0.25%) and a normal amount of calcium (0.5%) for 4 weeks reverses the growth retardation and the impaired mineralization in VDR KO mice, as does a high-calcium and high-phosphorus diet (Ca: 2%; P: 1.25%). Thus, the present study suggests that mobilization of calcium and mobilization of phosphorus are differentially regulated through vitamin D-dependent and -independent systems, and that intake of calcium and phosphorus in the proper ratio is important for mineral homeostasis and bone mineralization.

SummaryThis study aimed to clarify the regulatory mechanism of Mg homeostasis on administration of excessive Mg in rats. Six-week-old male Wistar rats ( n ϭ 30) were fed a Mgdeficient diet (D) or a control diet (M) in addition to which they received subcutaneous injections of saline (S) or additional Mg (M) for 14 d. Feces and urine were collected from the rats for 4 d every week. Between the MS and MM rats and the DS and DM rats, the injection of additional Mg increased Mg retention, but intestinal Mg absorption did not differ. Urinary Mg excretion in the MM rats was significantly greater than that in the MS rats, but fecal Mg excretion did not increase. Mg retention in the DM rats was approximately 30% of that in the MS rats, and urinary Mg excretion did not differ between the 2 groups, although the serum Mg in DM rats was low. There was no significant difference in the femoral Mg between the MM and MS groups. The physiological Mg pool in the bone appears to be limited. Therefore, there is no physiological Mg pool for the storage of excessive Mg, and there appears to be no negative feedback mechanism on intestinal Mg absorption upon administration of excessive Mg in the rats. In conclusion, it appears that the kidney is the only organ that regulates Mg in the body; apart from this, regulatory mechanisms corresponding to the physiological Mg requirement do not exist or are weak.

We investigated the influence of Mg feeding frequency on the variation in serum Mg concentration and tissue Mg levels in Mg-deficient rats. Sprague-Dawley rats, which had been fed a Mg-deficient diet for 14 d, were divided into 3 groups that were kept on 3 diets differing in their Mg content. The rats were fed 0.5-fold (Mg250 group), 1-fold (Mg500 group), or 1.5-fold (Mg750 group) the amounts of recommended Mg in their standard AIN-93G diet (Mg: 478 mg/kg diet) during the recovery period (12 d). The Mg500 and Mg750 groups were intermittently fed (Mg500, every 2 d; Mg750, every 3 d) so that their total intake of Mg during the recovery period could equal the Mg intake of the Mg250 group. The serum Mg concentrations increased in the 3 groups after feeding with a Mg-containing diet. However, serum Mg levels were only maintained within the normal range in the Mg250 group. After feeding on the Mg-deficient diet, in the intermittently fed groups, serum Mg concentrations decreased. Urinary Mg excretion was higher and Mg retention was lower in the Mg500 and Mg750 groups than in the Mg250 group. Moreover, bone Mg, especially elutable bone Mg, was lower in the Mg500 and Mg750 groups than in the Mg250 group. The elutable fraction of bone Mg correlated to the coefficient of variation of serum Mg concentration. In conclusion, for the maintenance of serum Mg concentration, it is important to increase the amount of elutable bone Mg by frequent Mg consumption.