Skeletal and Hormonal Effects of Magnesium Deficiency

Abstract

Magnesium (Mg) is the second most abundant intracellular cation where it plays an important role in enzyme function and trans-membrane ion transport. Mg deficiency has been associated with a number of clinical disorders including osteoporosis. Osteoporosis is common problem accounting for 2 million fractures per year in the United States at a cost of over $17 billion dollars. The average dietary Mg intake in women is 68% of the RDA, indicating that a large proportion of our population has substantial dietary Mg deficits. The objective of this paper is to review the evidence for Mg deficiency-induced osteoporosis and potential reasons why this occurs, including a cumulative review of work in our laboratories and well as a review of other published studies linking Mg deficiency to osteoporosis. Epidemiological studies have linked dietary Mg deficiency to osteoporosis. As diets deficient in Mg are also deficient in other nutrients that may affect bone, studies have been carried out with select dietary Mg depletion in animal models. Severe Mg deficiency in the rat (Mg at <0.0002% of total diet; normal = 0.05%) causes impaired bone growth, osteopenia and skeletal fragility. This degree of Mg deficiency probably does not commonly exist in the human population. We have therefore induced dietary Mg deprivation in the rat at 10%, 25% and 50% of recommended nutrient requirement. We observed bone loss, decrease in osteoblasts, and an increase in osteoclasts by histomorphometry. Such reduced Mg intake levels are present in our population. We also investigated potential mechanisms for bone loss in Mg deficiency. Studies in humans and and our rat model demonstrated low serum parathyroid hormone (PTH) and 1,25(OH)(2)-vitamin D levels, which may contribute to reduced bone formation. It is known that cytokines can increase osteoclastic bone resorption. Mg deficiency in the rat and/or mouse results in increased skeletal substance P, which in turn stimulates production of cytokines. With the use of immunohistocytochemistry, we found that Mg deficiency resulted in an increase in substance P, TNFalpha and IL1beta. Additional studies assessing the relative presence of receptor activator of nuclear factor kB ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG), found a decrease in OPG and an increase in RANKL favoring an increase in bone resorption. These data support the notion at dietary Mg intake at levels not uncommon in humans may perturb bone and mineral metabolism and be a risk factor for osteoporosis.

Reported zinc, but not copper, intakes influence whole-body bone density, mineral content and T score responses to zinc and copper supplementation in healthy postmenopausal women

“…Bone mineral contents, densities and T scores were neither improved in women consuming , 0·9 mg/d Cu, nor exacerbated in women consuming $0·9 mg/d Cu, by the Zn plus Cu supplement. However, Cu intake might have had some effect on the Baseline 217 767 32 770 29 12·9 0·5 12·9 0·4 3·28 0·23 3·13 0·23 Year 1 181 803 36 771 31 13·3 0·6 12·5 0·4 3·50 0·25 3·18 0·23 Year 2 167 824 37 838 43 12·9 0·5 13·2 0·6 3·70 0·28 3·25 0·25 Post-year 3 150 804 34 802 37 13·0 0·5 12·4 0·5 3·73 0·28 3·30 (16) , and Mg deficiency may be a risk factor for bone loss in postmenopausal women (17) . Thus, an analysis was made of whether the negative response to Zn supplementation was greater with Mg intakes ,237 mg/d through exacerbating the negative effect of Mg deprivation on bone health.…”

Magnesium substitution effect on porous scaffolds for bone repair

“…A very interesting result of this study was that the variants containing Mg slightly increased cell adhesion capacity. It is also demonstrated that Mg is closely associated with the mineralization of calcified tissues, directly stimulating osteoblast proliferation [9]. In addition to chemistry, the dimension of ceramic crystals is a factor implicated in the first phase of cell-biomaterial interactions.…”

“…In this process, Mg inhibits calcium phosphate cluster growth and stabilizes the amorphous state of bone mineral apatites [8]. Mg depletion alters bone and mineral metabolism and results in bone loss [9], and has been considered a risk factor for osteoporosis [10]. Experimental Mg deficiency in rats causes abnormalities in skeletal structure, enzyme (i.e., alkaline phosphatase) activity and bone mineralization that resemble some of those seen in several clinical bone diseases [11].…”

The Role of Vitamin K in Bone Remodeling and Osteoporosis

“…It is well known that a marked reduction of calcium causes a decrease of bone mass in rats (Rude, Singer, & Gruber, 2009). Numerous studies that have reported the beneficial effects of MKS on osteopenia and calcium homeostasis in rats with calcium deficiency A diet low in calcium (80-100 mg /day versus 800-1200 mg /day) reduced femoral BMD in rats by 12%.…”

“…Magnesium deficiency reduces bone strength in the femur with no significant changes in the cortical BMD and cortical thickness (Rude, Singer, & Gruber, 2009). The administration of MKS in these rats does not alter the value of femoral BMD or the thickeness of bone tissue.…”