Changes in circulating levels of fibroblast growth factor 23 induced by short-term dietary magnesium deficiency in rats.

Fibroblast growth factor 23 (FGF23) is a potent regulator of phosphorus (P) and vitamin D metabolism. Long-term dietary magnesium (Mg) deficiency increases circulating levels of FGF23, whereas the effects of short-term dietary Mg deficiency are unclear. Thus, the present study investigated whether short-term dietary Mg deficiency affects circulating levels of FGF23. We also assessed changes in renal mRNA expression of vitamin D metabolizing enzymes and type II sodium-phosphate (Na/Pi) cotransporters, since these are regulated by FGF23. Rats were fed a control diet (control group) or an Mg-deficient diet (Mg-deficient group) for 2, 4 or 7 days. Serum Mg levels were significantly lower in the Mg-deficient group than in the control group at all time points. Serum FGF23 levels were significantly higher in the Mg-deficient group than in the control group at day 7. The 25-hydroxyvitamin D-24-hydroxylase (24(OH)ase) mRNA levels were significantly higher in the Mg-deficient group than in the control group at day 7 . No significant differences in types IIa and IIc Na/Pi cotransporter mRNA levels were observed between the control and Mg-deficient groups. These results suggest that dietary Mg deficiency causes a rapid increase in circulating levels of FGF23 and renal 24(OH)ase mRNA levels.

Zinc Deficiency Increases Serum Concentrations of Parathyroid Hormone through a Decrease in Serum Calcium and Induces Bone Fragility in Rats.

We hypothesized that a zinc-deficient diet alters the mineral (calcium, magnesium, and phosphorus) components of bones, as well as hormones related to bone remodeling, and negatively affects bone metabolism. Four-week-old male Wistar rats were randomly assigned to one of three groups for 4 wk: a zinc-adequate group (C, 30 ppm); a zinc-deficient group (ZD, 1 ppm); and a pair-fed group (PF, 30 ppm), which was pair-fed to the ZD group. Bone mineral density and bone mechanical properties were reduced in the ZD group compared to the C and PF groups. Compared with the C and PF groups, serum osteocalcin, a bone formation marker, was reduced in the ZD group. Conversely, urine deoxypyridinoline, a bone resorption marker, was increased in the ZD group compared to the C and PF groups. Calcium and phosphorus concentrations in bone were not different among all groups. The bone magnesium concentration was significantly higher in the ZD group than in the PF and C groups. Interestingly, compared with the C and PF groups, the ZD group showed a reduction in serum calcium concentration along with an increase in serum parathyroid hormone (PTH) concentration. Although serum 1,25-dihydroxycholecalciferol concentration was significantly higher in the ZD and PF groups than in the C group, the rate of apparent calcium absorption was significantly lower in the ZD group than in the C and PF groups. Therefore, zinc deficiency is suspected to cause an increase in serum PTH concentration owing to an inability to maintain calcium homeostasis, resulting in bone fragility.

Dietary calcium and phosphorus ratio regulates bone mineralization and turnover in vitamin D receptor knockout mice by affecting intestinal calcium and phosphorus absorption.

UNLABELLED: 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.

Magnesium deficiency increases serum fibroblast growth factor-23 levels in rats.

A magnesium (Mg)-deficient diet results in decreased serum phosphorus (P) levels and increased urinary P excretion; however, the mechanisms responsible for these effects are unclear. Fibroblast growth factor-23 (FGF-23) is a potent regulator of P homeostasis. To determine the mechanisms responsible for the change in serum levels and urinary excretion of P with Mg deficiency, the present study examined the effects of Mg deficiency on serum FGF-23 levels. Male rats were randomized by weight into two groups and fed a control diet (Mg concentration: 0.05%) or a Mg-deficient diet (Mg concentration: Mg-free) for 21 days. Serum P levels in rats fed the Mg-deficient diet were significantly lower than in rats fed the control diet. Furthermore, urinary P excretion was significantly higher in rats fed the Mg-deficient diet compared to rats fed the control diet. Conversely, the tubular reabsorption rate of P was significantly lower in rats fed the Mg-deficient diet than in the controls. Serum FGF-23 levels in rats fed the Mg-deficient diet were significantly higher than those in animals fed the control diet. The results from the present study indicate that 1) Mg deficiency increases serum FGF-23 levels; and 2) Mg deficiency causes increased urinary P excretion via inhibition of renal P reabsorption, resulting in a lowering of serum P levels. Moreover, we suggest that the high serum FGF-23 levels induced by Mg deficiency contribute to the decrease in renal P reabsorption.

Magnesium deficiency regulates vitamin D metabolizing enzymes and type II sodium-phosphate cotransporter mRNA expression in rats.

A magnesium (Mg) deficiency induces changes in calcium (Ca) and phosphorus (P) metabolism; however, the mechanisms responsible for these effects remain unclear. Since 1,25-dihydroxyvitamin D3 and type II sodium-phosphate (Na/Pi) cotransporters are essential regulators of Ca and P metabolism, this study examined the effects of Mg deficiency on the mRNA expression of vitamin D metabolizing enzymes (25-hydroxyvitamin D-1α-hydroxylase (1α(OH)ase) and 25-hydroxyvitamin D-24-hydroxylase (24(OH)ase)), and Na/Pi cotransporters (type IIa and IIc) in the rat kidney. Rats were divided into two groups and fed a control diet (Mg concentration: 0.05%) or a Mg-deficient diet (Mg concentration: Mg-free) for 21 days. 1α(OH)ase mRNA levels were significantly decreased in rats fed the Mg-deficient diet, while 24(OH)ase mRNA levels were significantly increased, compared to rats fed the control diet. Type IIa and IIc Na/Pi cotransporter mRNA levels in rats fed the Mg-deficient diet were significantly decreased compared to rats fed the control diet. These results suggest that Mg deficiency induces downregulation of 1α(OH)ase and type IIa and IIc Na/Pi cotransporters, and upregulation of 24(OH)ase in the kidney.

Effects of a high-calcium diet on serum insulin-like growth factor-1 levels in magnesium-deficient rats.

In order to clarify the effects of a high-calcium (Ca) diet on bone formation in magnesium (Mg)-deficient rats, this study focused on the effects of a high-Ca diet on serum insulin-like growth factor-1 (IGF-1) levels. Male rats were randomized by weight into four groups, and fed one of four experimental diets containing two different Mg concentrations (0.05% (normal-Mg) or Mg-free (Mg-deficient)), and two different Ca concentrations (0.5% (normal-Ca) or 1.0% (high-Ca)) for 14 days. Serum concentrations of osteocalcin and IGF-1 were significantly lower in rats fed the Mg-deficient diet than in rats fed the normal-Mg diet. On the other hand, dietary Ca concentration had no significant influence on serum concentrations of osteocalcin and IGF-1. This study suggested that: 1) a high-Ca diet has no preventive effects on the decreased bone formation seen in Mg-deficient rats; and 2) a high-Ca diet does not enhance serum IGF-1 levels in Mg-deficient rats. Moreover, unchanged serum IGF-1 concentrations may contribute to the decreased bone formation seen in Mg-deficient rats receiving a high-Ca diet.