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. 2005 Sep 14;2(1):24.
doi: 10.1186/1743-7075-2-24.

Immunolocalization of RANKL is increased and OPG decreased during dietary magnesium deficiency in the rat

Robert K Rude  1 , Helen E Gruber, Livia Y Wei, Angelica Frausto
Affiliations

Immunolocalization of RANKL is increased and OPG decreased during dietary magnesium deficiency in the rat

Robert K Rude et al. Nutr Metab (Lond). .

Abstract

Background: Epidemiological studies have linked low dietary magnesium (Mg) to low bone mineral density and osteoporosis. Mg deficiency in animal models has demonstrated a reduction in bone mass and increase in skeletal fragility. One major mechanism appears to be an increase in osteoclast number and bone resorption. The final pathway of osteoclastogenesis involves three constituents of a cytokine system: receptor activator of nuclear factor kB ligand (RANKL); its receptor, receptor activator of nuclear factor kB (RANK); and its soluble decoy receptor, osteoprotegerin (OPG). The relative presence of RANKL and OPG dictates osteoclastogenesis. The objective of this study was to assess the presence of RANKL and OPG in rats on a low Mg diet.

Methods: RANKL and OPG were assessed by immunocytochemistry staining in the tibia for up to 6 months in control rats on regular Mg intake (0.5 g/kg) and experimental rats on reduction of dietary Mg (.04%, 25% and 50% of this Nutrient Requirement).

Results: At all dietary Mg intakes, alteration in the presence of immunocytochemical staining of RANKL and OPG was observed. In general, OPG was decreased and RANKL increased, reflecting an alteration in the RANKL/OPG ratio toward increased osteoclastogenesis.

Conclusion: We have, for the first time demonstrated that a reduction in dietary Mg in the rat alters the presence of RANKL and OPG and may explain the increase in osteoclast number and decrease in bone mass in this animal model. As some of these dietary intake reductions in terms of the RDA are present in a large segment of or population, Mg deficiency may be another risk factor for osteoporosis.

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Figures

Figure 1
Figure 1
Immunocytochemical staining of RANKL in bone from Mg deficient and control animals. A. Represents animals on a 25% NR diet and B. the control group. Note the positive staining of osteoclasts (solid arrows) and osteoblasts (open arrows) in A. while minimal staining is observed the control animals (B). C. Represents animals on a 50% NR diet and D. the control group. Again, as observed in C., Mg deficient animals have much more intense staining of RANKL of osteoclasts (solid arrows) and osteoblasts (open arrows) than is observed the control animals (D).
Figure 2
Figure 2
Immunocytochemical staining of OPG in bone from Mg deficient and control animals. A. Represents animals on a 25% NR diet and B. the control group. Note the minimal staining of osteoclasts (solid arrows) and osteoblasts (open arrows) in A. while positive staining is observed the control animals (B). C. Represents animals on a 50% NR diet and D. the control group. Again, as observed in C., Mg deficient animals have minimal staining for OPG in osteoclasts (solid arrows) and osteoblasts (open arrows), while much more intense staining is observed in the control animals (D).
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