Dietary Magnesium Intake and Osteoporosis
October 2000; Volume 2; 73-77
By Robert K. Rude, MD
A common clinical condition, osteoporosis is characterized by low bone mass and an increased propensity for fracture. Known risk factors include hereditary predisposition, female gender, excessive alcohol intake, smoking, and dietary factors (calcium and vitamin D deficiency). Magnesium (Mg) deficiency also has been implicated as a risk factor for osteoporosis. Mg is the second most prevalent intracellular cation in the body, where it plays important roles in enzyme activity, membrane stability, and ion transport.1
The U.S. Food and Nutrition Board recently changed the Recommended Daily Allowance for Mg for adult males to 420 mg/d and for adult females to 320 mg/d.2 However, in a large proportion of the population, the usual dietary Mg intake falls below this recommendation. According to the USDA, the mean Mg intake for males is 323 mg/d and for females is 228 mg/d.3 For individuals over age 70 (those at greatest risk for fracture), Mg intake is the lowest for any adult group. Severe Mg deficiency markedly perturbs calcium homeostasis, resulting in impaired parathyroid hormone (PTH) secretion and PTH end-organ resistance that can lead to hypocalcemia and neuromuscular hyperexcitability.1 The effect of more mild degrees of Mg deficiency on the skeleton is relatively unexplored. This paper is a review of human and animal studies designed to assess the role of dietary Mg intake in the development of osteoporosis. (See Table 1 for dietary sources of Mg.)
| Table 1-Dietary sources of magnesium | ||
| Food Source | Serving Size | Magnesium Content |
| 100% bran | 1 oz | 134 mg |
| Florida avocado | 1/2 med | 103 mg |
| Toasted wheat germ | 1 oz | 90 mg |
| Dry roasted almonds | 1 oz | 86 mg |
| Shredded wheat cereal | 2 biscuits | 80 mg |
| Pumpkin seeds | 1/2 oz | 75 mg |
| Dry roasted cashews | 1 oz | 73 mg |
| Cooked spinach | 1/2 cup | 65 mg |
| Baked potato with skin | 1 med | 55 mg |
| Cooked soybeans | 1/2 cup | 54 mg |
| Chocolate bar | 1.45 oz | 45 mg |
| http://www.cc.nih.gov/ccc/supplements/magn.html. Accessed September 12, 2000. |
||
Epidemiological Studies
The major link between inadequate Mg intake and osteoporosis has come from epidemiologic studies. Most studies have shown a correlation; there may be gender differences. One cross-sectional study assessed the effect of dietary nutrients on bone mineral density (BMD).4 In 1,208 Japanese-American males (ages 61-81) living in Hawaii, whose mean Mg intake was 238 mg/d, Mg intake did not correlate with BMD at any site. However, in a subgroup of 259 of these subjects who took Mg supplements (mean Mg intake 381 mg/d), BMD was positively correlated with Mg intake. In 912 females (ages 43-80) whose Mg intake was 191 mg/d, a positive correlation with BMD was observed. In contrast to the males, no correlation with BMD was found in females who took Mg supplements (total Mg intake of 321 mg/d).
In a smaller study of women ages 35-65 (17 premenopausal, mean Mg intake 243 mg/d; 67 postmenopausal, mean Mg intake 249 mg/d) in which BMD was measured in the distal forearm, no cross-sectional correlation with Mg intake in either group was observed.5 Longitudinal observation over four years, however, demonstrated that loss of bone mass was inversely related to Mg intake in premenopausal women (P < 0.05); there was no significant change in the postmenopausal group. In another cross-sectional study, a positive correlation of Mg intake with BMD of the forearm was found in 89 premenopausal women (mean age 37.8; Mg intake 243 mg/d), but not in 71 postmenopausal women (mean age 58.9; Mg intake 253 mg/d).6 In contrast, another study demonstrated a significant positive correlation between BMD of the forearm in 194 older postmenopausal women (ages 69-97) and Mg intake (mean 288 mg/d).7
A more recent one-year study of 66 premenopausal women (ages 28-39; mean Mg intake 289 mg/d) found a significant relationship between dietary Mg intake and rate of change of BMD in the lumbar spine; there also was a correlation with total body calcium.8 However, a cross-sectional study that included 175 women (ages 28-74, mean Mg intake 262 mg/d) found no correlation with BMD at the lumbar spine, femoral neck, or total body calcium.9 In a study of 994 premenopausal women (ages 45-49; mean Mg intake 311 mg/d), New et al found a significant correlation between lumbar spine BMD with Mg intake.10 A significant difference also was observed in lumbar spine BMD between the highest and lowest quartiles of dietary Mg intake. In a study of 65 women (ages 45-55), this same group again found higher bone mass of the forearm (but not femoral neck or hip) in subjects who consumed a mean Mg intake of 326 mg/d.11 Tucker et al assessed Mg intake in older males and females (ages 69-97) in a cross-sectional study (345 male; 562 female) and a two-year longitudinal study of a subset of these subjects (229 male; 399 female).12 In the cross-sectional analysis in males, Mg intake (300 mg/d) was correlated with BMD of the radius and hip. In the four-year longitudinal study of these subjects, a positive inverse relationship between bone loss of the hip and Mg intake was observed. Positive cross-sectional correlation of BMD of the hip also was observed in females (Mg intake 288 mg/d), but not in the longitudinal assessment.
Lastly, another investigation evaluated the effect of dietary Mg intake of preadolescent girls (ages 9-11) on bone mass/quality in these same young women at ages 18-19.13 Ultrasound determination of bone mass of the calcaneus in 35 African-American women (Mg intake 237 mg/d) and 26 white women (Mg intake 240 mg/d) was performed. Mg intake was positively related to quantitative ultrasound properties of bone, suggesting that this nutrient was important in skeletal growth and development.
In summary, these epidemiological studies link dietary Mg intake to bone mass. Exceptions appear to include women in the early postmenopausal period, perhaps because the effect of acute sex steroid deficiency may mask the effect of dietary factors such as Mg. In addition, diets deficient in Mg usually are deficient in other nutrients as well. Therefore, further investigations are needed to provide a firm relationship of dietary Mg inadequacy with osteoporosis.
Dietary Mg Intake and Bone Turnover
High bone turnover has been suggested to indicate a greater risk for bone loss and osteoporosis. In two of the epidemiological studies cited above, markers of bone turnover were determined. In the first, where no correlation was found between BMD and dietary Mg intake, serum osteocalcin did not correlate with dietary intake of Mg (or any other nutrient).9 In the study by New et al, serum osteocalcin also was not associated with dietary intake of Mg or any other nutrient.11 Low Mg intake, however, seemed to reflect bone resorption, as intake was significantly negatively correlated with pyridinoline and deoxypyridinoline excretion.11
Mg Status in Osteoporosis
Despite interest in the possible role that dietary Mg insufficiency may play as a risk factor for osteoporosis, few studies have been conducted assessing Mg status in patients with osteoporosis. One study reported on a small group of 15 osteoporotic subjects (10 female, 5 male) ages 70-85 (the presence or absence of osteoporosis was determined by radiographic features) compared to 10 control non-osteoporotic subjects.14 Both groups had normal serum Mg concentrations and were not significantly different from each other. However, the Mg tolerance test resulted in a significantly greater retention in the osteoporotic patients, 38% as compared to 10% in the control subjects. The Mg tolerance test usually is performed by collecting a 24-hour urine for Mg and creatinine. A small amount of Mg (0.2 mEq/kg body weight) is then infused over four hours. A second 24-hour urine is collected for Mg and creatinine beginning with the Mg infusion. The amount of Mg excreted above baseline represents the amount not retained by the body. In Mg deficiency, most of the Mg will be retained and very little Mg excreted into the urine. In contrast, a normal Mg-replete person will excrete > 90% of that infused.
In another study by this same group, 12 younger women ages 55-65 with osteoporosis had significantly lower serum Mg concentrations than 10 control subjects; however, no difference in Mg tolerance was observed.15 Another study found red blood cell Mg to be significantly lower in 10 postmenopausal women who had at least one vertebral fracture as compared to 10 subjects with degenerative osteoarthritis.16 No difference in plasma Mg was found. In a second study by this group, 10 postmenopausal women age 68.9 ± 9 with vertebral crush fracture were compared to 10 non-osteoporotic women age 67.2 ± 6 years.17 In comparison to the 10 controls, the osteoporotic subjects had significantly lower serum Mg, but no difference was noted in red blood cell Mg.
Fifty to sixty percent of body Mg resides in the skeleton, and skeletal Mg content has been considered to reflect Mg status. In the two studies cited above in which a Mg deficit was suggested by either Mg tolerance testing or low serum Mg concentration, Mg content of trabecular bone was significantly reduced in the osteoporotic patients.14,15 Two additional studies also found a lower bone Mg content in elderly osteoporotic patients.18,19 Other studies, however, found no difference in Mg content of bone between subjects with normal bone mass and osteoporotic patients.17,20
Mg Therapy in Osteoporosis
Some studies have evaluated the effect of dietary Mg supplementation on bone mass in patients with osteoporosis. Abraham et al administered 600 mg/d Mg to 19 patients over 6-12 months.21 BMD of the calcaneus increased 11% compared to a 0.7% rise in seven control subjects. All subjects were postmenopausal (ages 42-75) and were taking hormone replacement therapy. However, the subjects who received Mg also received 500 mg/d calcium and many other dietary supplements, making it difficult to conclude that Mg alone was the sole reason for the increase in bone mass.
In a retrospective study, six postmenopausal women (mean age 59; Mg intake 200 mg/d for six months) were observed to have no significant change in bone density of the lumbar spine or the femur.22 Stendig-Linberg et al conducted a two-year trial in which 31 postmenopausal osteoporotic women were administered 250 mg/d Mg increasing to a maximum of 750 mg/d for six months depending on tolerance.23 All subjects were given 250 mg/d Mg from months six to 24. Twenty-three age-matched subjects served as control. At one year there was a significant 2.8% increase in bone density of the distal radius. Twenty-two of the 31 subjects had an increase in bone density while five did not change. Three subjects who showed a decrease in bone density had primary hyperparathyroidism and one other subject underwent a thyroidectomy. No significant effect of Mg supplementation was shown at two years, although only 10 subjects completed the second year of the trial. In a small uncontrolled trial, a significant increase in bone density of the proximal femur and lumbar spine was seen in celiac sprue patients who received approximately 575 mg/d Mg.24 These subjects had demonstrated evidence of reduced Mg in red blood cells and peripheral lymphocytes.
Mg Depletion and Osteoporosis: Experimental Animal Models
The effect of dietary Mg depletion on bone and mineral homeostasis has been studied extensively in the rat (for review and reference see references 1 and 25). Dietary restriction usually was severe. A universal observation was a decrease in growth of both the whole body as well as the skeleton. The epiphyseal and diaphyseal growth plate is characterized by thinning and a decrease in the number and organization of chondrocytes. Osteoblastic bone formation was reduced by quantitative histomorphometry. Serum and bone alkaline phosphatase, serum and bone osteocalcin, and bone osteocalcin mRNA were reduced, suggesting decreased osteoblastic function. Data on osteoclast function have been conflicting. A decrease in urinary hydroxyproline and deoxypyridinoline suggests a decrease in bone resorption; however, a recent study reported an increase in the number and activity of osteoclasts in the Mg-deficient rat. Osteoporosis occurred within six weeks and the bone from the Mg-deficient rat was described as brittle and fragile. Biomechanical testing directly demonstrated skeletal fragility in both rat and pig.
Possible Mechanisms for Osteoporosis in Mg Deficiency
Several potential mechanisms may account for decrease in bone mass in Mg deficiency (for review and reference see references 1 and 25). Mg is mitogenic for bone cell growth, which may directly result in a decrease in bone formation. Mg also affects crystal formation; a lack of Mg results in a larger, more perfect crystal that may affect bone strength. Mg deficiency will result in impaired PTH secretion as well as an end-organ resistance to PTH-action. Serum 1,25(OH)2 vitamin D levels also are low in Mg-deficient humans. Both hormones are trophic for bone and their deficiency may result in decrease in bone formation. Serum IGF-1 levels also have been observed to be low in the Mg-deficient rat, which could affect skeletal growth. While the above may explain low bone formation, it does not explain the observation of an increase in osteoclast bone resorption. Acute Mg depletion in the rat and mouse have demonstrated an immediate rise in substance P followed by a rise in inflammatory cytokines. These cytokines could contribute to an increase in osteoclastic bone resorption and explain the uncoupling of bone formation and bone resorption observed in the rat. Whether these possibilities are valid for suboptimal chronic dietary Mg deficit in human osteoporosis in unknown. Further studies are needed to explore these possibilities.
Dr. Rude is Professor of Medicine at the University of California School of Medicine in Los Angeles.
References
1. Rude RK. Magnesium deficiency: A heterogenous cause of disease in humans. J Bone Min Res 1998;13:749-758.
2. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academy Press; 1997:190-249.
3. Cleveland LE, et al. Data tables: Results from USDA’s 1994 continuing survey of food intakes by individuals and 1994 diet and health knowledge survey. Beltsville, MD: Agricultural Research Service, U.S. Department of Agriculture.
4. Yano K, et al. The relationship between diet and bone mineral content of multiple skeletal sites in elderly Japanese-American men and women living in Hawaii. Am J Clin Nutr 1985;42:877-888.
5. Freudenheim JL, et al. Relationships between usual nutrient intake and bone-mineral content of women 35-65 years of age: Longitudinal and cross-sectional analysis. Am J Clin Nutr 1986;44;863-876.
6. Angus RM, et al. Dietary intake and bone mineral density. Bone Miner 1988;4:265-277.
7. Tranquilli AL, et al. Calcium, phosphorus and magnesium intakes correlate with bone mineral content in postmenopausal women. Gynecol Endocrinol 1994;8:55-58.
8. Houtkooper LB, et al. Nutrients, body composition and exercise are related to change in bone mineral density in premenopausal women. J Nutr 1995;125:1229-1237.
9. Michaelsson K, et al. Diet, bone mass, and osteocalcin: A cross-sectional study. Calcif Tissue Int 1995;57:86-93.
10. New SA, et al. Nutritional influences on bone mineral density: A cross-sectional study in premenopausal women. Am J Clin Nutr 1997;65:1831-1839.
11. New SA, et al. Dietary influences on bone mass and bone metabolism: Further evidence of a positive link between fruit and vegetable consumption and bone health? Am J Clin Nutr 2000;71:142-151.
12. Tucker KL, et al. Potassium, magnesium and fruit and vegetable intakes are associated with greater bone mineral density in elderly men and women. Am J Clin Nutr 1999;69:727-736.
13. Wang MC, et al. Influence of pre-adolescent diet on quantitative ultrasound measurements of the calcaneus in young adult women. Osteoporos Int 1999;9:532-535.
14. Cohen L, Kitzes AL. Bone magnesium, crystallinity index and state of body magnesium in subjects with senile osteoporosis, maturity-onset diabetes and women treated with contraceptive preparations. Magnes 1983;2:70-75.
15. Cohen L, et al. Magnesium malabsorption in postmenopausal osteoporosis. Magnes 1983;2:139-143.
16. Reginster JY, et al. Serum and erythrocyte magnesium in osteoporotic and osteoarthritic postmenopausal women. Magnes 1985;4:208.
17. Reginster JY. Serum magnesium in postmenopausal osteoporosis. Magnes 1989;8:106.
18. Manicourt DH, et al. Bone mineral content of the radius: Good correlations with physicochemical determinations in iliac crest trabecular bone of normal and osteoporotic subjects. Metabolism 1981;30:57-62.
19. Milachowski K, et al. Die bedeutung des magnesiums beider medialen schenkelhasfrakur des alter menschen. Magnes Bull 1981;3:90-102.
20. Burnell JM, et al. Bone matrix and mineral abnormalities in postmenopausal osteoporosis. Metabolism 1982;31:1113-1120.
21. Abraham GE. The importance of magnesium in the management of primary postmenopausal osteoporosis. J Nutr Med 1991;2:165-178.
22. Eisinger J, Clairet D. Effects of silicon, fluoride, etidronate and magnesium on bone mineral density: A retrospective study. Magnes Res 1993;6:247-249.
23. Stendig-Lindberg G, et al. Trabecular bone density in a two year controlled trial of peroral magnesium in osteoporosis. Magnes Res 1993;6:155-163.
24. Rude RK, Olerich M. Magnesium deficiency: Possible role in osteoporosis associated with gluten-sensitive enteropathy. Osteoporos Int 1996;6:453-461.
25. Rude RK, et al. Chronic dietary-induced magnesium deficiency alters bone and mineral homeostasis in the rat. Magnes Res 1999;12:257-267.
October 2000; Volume 2; 73-77
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content