Magnesium Deficiency: Effect on Bone and Mineral Metabolism in the Mouse

Abstract

Insufficient dietary magnesium (Mg) intake has been associated in humans with low bone mass. Mg deficiency in the rat has suggested bone loss is due to increased bone resorption and/or inadequate bone formation during remodeling. The purpose of this study was to assess the effect of a low Mg diet on bone and mineral metabolism in the young and mature BALB/c mouse and explore the hypothesis that inflammatory cytokines may contribute to Mg deficiency-induced osteoporosis. Using an artificial diet, we induced targeted Mg depletion (0.002% Mg) with all other nutrients maintained at the normal level. In all Mg-depleted mice, hypomagnesemia developed and skeletal Mg content fell significantly. The serum Ca in Mg-deficient mice was higher than in control mice; however, serum PTH levels were not significantly different. Osteoprotegerin (OPG) in dosages that inhibit osteoclastic bone resorption did not prevent hypercalcemia in Mg-deficient animals. No significant difference in serum Ca was observed between groups when dietary Ca was reduced by 50%, suggesting that a compensatory increase in intestinal absorption might account for the hypercalcemia. Growth plate width decreased 33% in young Mg-deficient animals and chondrocyte columns decreased in number and length, suggesting that Mg deficiency reduced bone growth. Trabecular bone volume in the metaphysis of the tibia in these animals was decreased and osteoclast number was increased by 135%. Osteoblast number was significantly reduced. Immunohistochemistry revealed that substance P increased 230% and 200% in megakaryocytes and lymphocytes, respectively, after 1 day of Mg depletion. IL-1 increased by 140% in osteoclasts by day 3 and TNF alpha increased in osteoclasts by 120% and 500% in megakaryocytes on day 12. This study demonstrates a profound effect of Mg depletion on bone characterized by impaired bone growth, decreased osteoblast number, increased osteoclast number in young animals, and loss of trabecular bone with stimulation of cytokine activity in bone.

Probing the calcium and sodium local environment in bones and teeth using multinuclear solid state NMR and X-ray absorption spectroscopy

“…8,10 Although they are present in very small quantities, these ions often have a strong influence on the functional properties of bone and teeth. For example, sodium plays a role in bone remodeling, 11 magnesium deficiency leads to an increase in osteoclastic bone resorption, 12 and fluoride helps prevent the development of dental caries. 13 Infra-red (IR) spectroscopy, [14][15][16] XRD, 17,18 and X-ray absorption spectroscopy, [19][20][21] have played their part in unravelling the complexity of the mineral structure.…”

Molecular Determinants of Magnesium Homeostasis

“…26 Consistent with this notion, animals fed Mg 2ϩ -deficient diets have a bone Mg 2ϩ content that is reduced by 30 to 40% and a reduced bone mineral density. [27][28][29] This is mediated by a decrease in the number of osteoblasts, with inhibited function, 9,27,28 and an increase in both the number and function of osteoclasts. 9,[27][28][29] Finally, current data, although by no means conclusive, suggest that Mg 2ϩ deficiency predisposes an individual to osteoporosis.…”

“…[27][28][29] This is mediated by a decrease in the number of osteoblasts, with inhibited function, 9,27,28 and an increase in both the number and function of osteoclasts. 9,[27][28][29] Finally, current data, although by no means conclusive, suggest that Mg 2ϩ deficiency predisposes an individual to osteoporosis. 29 -32 Unfortunately, our understanding of the molecular details governing the incorporation of Mg 2ϩ into bone by osteoblasts and its retrieval by osteoclasts is minimal.…”

Biocompatibility and bioactivity of porous polymer-derived Ca-Mg silicate ceramics

“…Mg was suggested to interact with integrins of osteoblasts 17 that are responsible for cell adhesion and stability [23,50]. The importance of Mg in bone [25,51,52]. In addition to Mg, Ca 2+ and soluble silica were also released by the bioactive Ca-…”