Immunolocalization of RANKL is Increased and OPG Decreased During Dietary Magnesium Deficiency in the Rat

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

doi:10.1186/1743-7075-2-24

Abstract

BackgroundEpidemiological 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.MethodsRANKL 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).ResultsAt 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.ConclusionWe 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.

Highlights

Severe magnesium (Mg) deficiency (0.04% of nutrient requirement, NR)[1] results in osteoporosis in rodent models characterized by decreased bone formation, increased bone resorption, and increased skeletal fragility [2,3,4,5,6,7,8]
Epidemiologic studies have demonstrated a positive correlation between dietary Mg intake, and bone density and/or an increased rate of bone loss with low dietary Mg intake suggesting that dietary Mg deficiency may be a risk factor for osteoporosis [13,14,15,16,17,18]
In rats fed a diet containing 0.4% of NR, there was an increase in staining in many cells of the bone microenvironment; receptor activator of nuclear factor kB ligand (RANKL) was increased by 448% in osteoblasts on day 1, in lymphocytes by 157% on day 3 and 100% on day 8, and in osteoclasts by 64% on day 22

Summary

Introduction

Severe magnesium (Mg) deficiency (0.04% of nutrient requirement, NR)[1] results in osteoporosis in rodent models characterized by decreased bone formation, increased bone resorption, and increased skeletal fragility [2,3,4,5,6,7,8] This degree of Mg depletion rarely exists in humans; we have found that a more moderate dietary Mg restriction, 10% of NR and 25% of NR, results in bone loss in the rat [9,10]. We have recently found that a diet of 50% of NR causes a reduction in bone mass (submitted for publication) These studies suggest that an inadequate Mg intake may be a risk for osteoporosis. The objective of this study was to assess the presence of RANKL and OPG in rats on a low Mg diet

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Discussion

Conclusion