Monthly Archives: March 2014

Calcium Does Not Prevent Decreased Bone Formation From Magnesium Deficiency in Rats

Abstract

Effects of a high-calcium diet on serum insulin-like growth factor-1 levels in magnesium-deficient rats.

In order to clarify the effects of a high-calcium (Ca) diet on bone formation in magnesium (Mg)-deficient rats, this study focused on the effects of a high-Ca diet on serum insulin-like growth factor-1 (IGF-1) levels. Male rats were randomized by weight into four groups, and fed one of four experimental diets containing two different Mg concentrations (0.05% (normal-Mg) or Mg-free (Mg-deficient)), and two different Ca concentrations (0.5% (normal-Ca) or 1.0% (high-Ca)) for 14 days. Serum concentrations of osteocalcin and IGF-1 were significantly lower in rats fed the Mg-deficient diet than in rats fed the normal-Mg diet. On the other hand, dietary Ca concentration had no significant influence on serum concentrations of osteocalcin and IGF-1. This study suggested that: 1) a high-Ca diet has no preventive effects on the decreased bone formation seen in Mg-deficient rats; and 2) a high-Ca diet does not enhance serum IGF-1 levels in Mg-deficient rats. Moreover, unchanged serum IGF-1 concentrations may contribute to the decreased bone formation seen in Mg-deficient rats receiving a high-Ca diet.

Matsuzaki H, Kajita Y, Miwa M
Magnes Res
PMID: 22995212

Magnesium Not Associated with Bone Mass in Young Women

Abstract

Magnesium intake and bone mineral density in young adult women.

The purpose of this study was to determine a possible association between magnesium intake and bone mass in young adult women. Subjects consisted of 106 female university students aged 19-25 years. Calcium and magnesium intakes were evaluated using the duplicate sampling method on three weekdays. Spinal and femoral bone mineral density (BMD) was measured by dual energy X-ray absorptiometry. Mean magnesium intake was 139 mg/day (median 127, SD 54). The correlation between magnesium intake and BMD was of borderline significance (r = 0.175, p = 0.073) for the femoral neck, and was insignificant (r = 0.084, p = 0.391) for the lumbar spine. However, the partial correlation between magnesium intake and BMD of the femoral neck (r = -0.027, p = 0.788), adjusted for calcium intake, was not significant. In conclusion, we did not find an association between magnesium intake and bone mass in young women, and calcium intake needs to be included as an important, potential confounding factor when exploring such an association.

Nakamura K, Ueno K, Nishiwaki T, Saito T…
Magnes Res Dec 2007
PMID: 18271495 | Free Full Text

Review: Magnesium Deficiency Effects on Bone

Abstract

Skeletal and hormonal effects of magnesium deficiency.

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.

Rude RK, Singer FR, Gruber HE
J Am Coll Nutr Apr 2009
PMID: 19828898

Magnesium in Bone is Higher When Taken More Frequently in Rats

Abstract

The frequency of magnesium consumption directly influences its serum concentration and the amount of elutable bone magnesium in rats.

We investigated the influence of Mg feeding frequency on the variation in serum Mg concentration and tissue Mg levels in Mg-deficient rats. Sprague-Dawley rats, which had been fed a Mg-deficient diet for 14 d, were divided into 3 groups that were kept on 3 diets differing in their Mg content. The rats were fed 0.5-fold (Mg250 group), 1-fold (Mg500 group), or 1.5-fold (Mg750 group) the amounts of recommended Mg in their standard AIN-93G diet (Mg: 478 mg/kg diet) during the recovery period (12 d). The Mg500 and Mg750 groups were intermittently fed (Mg500, every 2 d; Mg750, every 3 d) so that their total intake of Mg during the recovery period could equal the Mg intake of the Mg250 group. The serum Mg concentrations increased in the 3 groups after feeding with a Mg-containing diet. However, serum Mg levels were only maintained within the normal range in the Mg250 group. After feeding on the Mg-deficient diet, in the intermittently fed groups, serum Mg concentrations decreased. Urinary Mg excretion was higher and Mg retention was lower in the Mg500 and Mg750 groups than in the Mg250 group. Moreover, bone Mg, especially elutable bone Mg, was lower in the Mg500 and Mg750 groups than in the Mg250 group. The elutable fraction of bone Mg correlated to the coefficient of variation of serum Mg concentration. In conclusion, for the maintenance of serum Mg concentration, it is important to increase the amount of elutable bone Mg by frequent Mg consumption.

Nakaya Y, Uehara M, Katsumata S, Suzuki K…
Magnes Res Mar 2010
PMID: 20228011 | Free Full Text

Note the rats that ate 250mg/kg Magnesium had higher bone Magnesium than the rats fed just as much Magnesium but less often, every 2 or 3 days.

Magnesium Deficiency Reduces Bone Mass in Rats

Abstract

Effects of magnesium intake deficiency on bone metabolism and bone tissue around osseointegrated implants.

This study evaluated the effect of magnesium dietary deficiency on bone metabolism and bone tissue around implants with established osseointegration.
For this, 30 rats received an implant in the right tibial metaphysis. After 60 days for healing of the implants, the animals were divided into groups according to the diet received. Control group (CTL) received a standard diet with adequate magnesium content, while test group (Mg) received the same diet except for a 90% reduction of magnesium. The animals were sacrificed after 90 days for evaluation of calcium, magnesium, osteocalcin and parathyroid hormone (PTH) serum levels and the deoxypyridinoline (DPD) level in the urine. The effect of magnesium deficiency on skeletal bone tissue was evaluated by densitometry of the lumbar vertebrae, while the effect of bone tissue around titanium implants was evaluated by radiographic measurement of cortical bone thickness and bone density. The effect on biomechanical characteristics was verified by implant removal torque testing.
Magnesium dietary deficiency resulted in a decrease of the magnesium serum level and an increase of PTH and DPD levels (P ≤ 0.05). The Mg [deficient] group also presented a loss of systemic bone mass, decreased cortical bone thickness and lower values of removal torque of the implants (P ≤ 0.01).
The present study concluded that magnesium-deficient diet had a negative influence on bone metabolism as well as on the bone tissue around the implants.

Belluci MM, Giro G, del Barrio RA, Pereira RM…
Clin Oral Implants Res Jul 2011
PMID: 21143536

Magnesium Suppresses Bone Turnover in Postmenopausal Women with Osteoporosis

Abstract

Short-term oral magnesium supplementation suppresses bone turnover in postmenopausal osteoporotic women.

Magnesium has been shown to increase bone mineral density when used in the treatment of osteoporosis, yet its mechanism of action is obscure. In this study, the effects of daily oral magnesium supplementation on biochemical markers of bone turnover were investigated. Twenty postmenopausal women have been divided into two groups. Ten patients were given magnesium citrate (1,830 mg/day) orally for 30 days. Ten postmenopausal women of matching age, menopause duration, and BMI were recruited as the control group and followed without any medication. Fasting blood and first-void urine samples were collected on days 0, 1, 5, 10, 20, and 30, respectively. Total magnesium, calcium, phosphorus, iPTH and osteocalcin were determined in blood samples. Deoxypyridinoline levels adjusted for creatinine were measured in urine samples. Thirty consecutive days of oral magnesium supplementation caused significantly decrease in serum iPTH levels in the Mg-supplemented group (p < 0.05). Serum osteocalcin levels were significantly increased (p < 0.001) and urinary deoxypyridinoline levels were decreased (p < 0.001) in the Mg-supplemented group. This study has demonstrated that oral magnesium supplementation in postmenopausal osteoporotic women suppresses bone turnover.

Aydin H, Deyneli O, Yavuz D, Gözü H…
Biol Trace Elem Res Feb 2010
PMID: 19488681

Magnesium Associated with Bone Density in Swimmers

Abstract

Magnesium intake mediates the association between bone mineral density and lean soft tissue in elite swimmers.

Magnesium (Mg) deficiency has been associated with bone disorders. Physical activity is also crucial for bone mineralization. Bone mass loss has been observed to be accelerated in subjects with low Mg intake. We aim to understand if Mg intake mediates the association between bone mineral density (BMD) and lean soft tissue (LST) in elite swimmers. Seventeen elite swimmers (eight males; nine females) were evaluated. Bone mineral content, BMD, LST, and fat mass were assessed using dual energy X-ray absorptiometry. Energy and nutrient intake were assessed during a seven-day period and analyzed with Food Processor SQL. Males presented lower values than the normative data for BMD. Mg, phosphorus (P) and vitamin D intake were significantly lower than the recommended daily allowance. A linear regression model demonstrated a significant association between LST and BMD. When Mg intake was included, we observed that this was a significant, independent predictor of BMD, with a significant increase of 24% in the R(2) of the initial predictive model. When adjusted for energy, vitamin D, calcium, and P intake, Mg remained a significant predictor of BMD. In conclusion, young athletes engaged in low impact sports, should pay special attention to Mg intake, given its potential role in bone mineral mass acquisition during growth.

Matias CN, Santos DA, Monteiro CP, Vasco AM…
Magnes Res
PMID: 23015157

Magnesium Deficiency Increases Resorption and Osteoclasts While Decreasing Bone Formation and Osteoblasts

Abstract

Magnesium deficiency-induced osteoporosis in the rat: uncoupling of bone formation and bone resorption.

Magnesium (Mg) intake has been linked to bone mass and/or rate of bone loss in humans. Experimental Mg deficiency in animal models has resulted in impaired bone growth, osteopenia, and increased skeletal fragility. In order to assess changes in bone and mineral homeostasis that may be responsible, we induced dietary Mg deficiency in adult Simonsen albino rats for 16 weeks. Rats were fed either a low Mg diet (0.002 percent) or a normal control Mg diet (0.063 percent). Blood was obtained at baseline, 4 weeks, 8 weeks, 12 weeks and 16 weeks in both groups for serum Mg, calcium, PTH, and 1.25(OH)2-vitamin D determinations. Femora were harvested at 4 weeks and 16 weeks for mineral analysis and histomorphometry. Serum Mg fell in the Mg depleted group to 0.6 mg/dl (mean) by 16 weeks (controls = 2.0 mg/dl). The serum calcium (Ca) concentration was higher in the Mg depleted animals at 16 weeks, 10.8 mg/dl (controls = 8.9 mg/dl). Serum PTH concentration fell progressively in the Mg deficient rats to 30 pg/ml by week 16 (control = 96 pg/ml). Serum concentration of 1.25(OH)2-vitamin D also fell progressively in the Mg deficient animals by 16 weeks to 14 pg/ml (control = 30 pg/ml). While the percent ash weights of Ca and phosphorus in the femur were not different at any time point, the percent ash weight of Mg progressively fell to 0.54 percent vs control (0.74 percent) by 16 weeks. The percent ash weight of potassium also fell progressively in the Mg deficient group to approximately 30 percent of control by 16 weeks. Histomorphometric analyses showed a significant drop in trabecular bone volume in Mg deficient animals by 16 weeks (percent BV/TV = 13.2 percent vs 17.3 percent in controls). Evaluation of the endosteal bone surface features showed significantly greater bone resorption in the Mg depleted group as reflected in increased number of tartrate-resistant positive osteoclasts/mm bone surface (7.8 vs 4.0 in controls) and an elevated percent of bone surface occupied by osteoclasts (percent OcS/BS = 12.2 percent vs 6.7 percent in controls. This increased resorption occurred in the presence of an inappropriate lowered bone forming surface relative to controls; a decreased number of osteoblasts per mm bone surface (0.23 vs 0.94 in control) and a decrease in percent trabecular surface lined by osteoid (percent OS/BS = 0.41 vs 2.27 percent in controls) were also noted. Our findings demonstrate a Mg-deficiency induced uncoupling of bone formation and bone resorption resulting in a loss of bone mass. While the fall in PTH and/or 1.25(OH)2-D may explain a decrease in osteoblast activity, the mechanism for increased osteoclast activity is unclear. These data suggest that Mg deficiency may be a risk factor for osteoporosis.

Rude RK, Kirchen ME, Gruber HE, Meyer MH…
Magnes Res Dec 1999
PMID: 10612083

Magnesium Reduces Bone Formation and Resorption in Young Men

Abstract

Daily oral magnesium supplementation suppresses bone turnover in young adult males.

This study examined the effects of daily oral magnesium (Mg) supplementation on bone turnover in 12 young (27-36 yr old) healthy men. Twelve healthy men of matching age, height, and weight were recruited as the control group. The study group received orally 15 mmol Mg (Magnosolv powder, Asta Medica) daily in the early afternoon with 2-h fasting before and after Mg intake. Fasting blood and second void urine samples were collected in the early morning on days 0, 1, 5, 10, 20, and 30, respectively. Total and ionized Mg2+ and calcium (Ca2+), and intact PTH (iPTH) levels were determined in blood samples. Serum biochemical markers of bone formation (i.e. C-terminus of type I procollagen peptide and osteocalcin) and resorption (i.e. type I collagen telopeptide) and urinary Mg level adjusted for creatinine were measured. In these young males, 30 consecutive days of oral Mg supplementation had no significant effect on total circulating Mg level, but caused a significant reduction in the serum ionized Mg+ level after 5 days of intake. The Mg supplementation also significantly reduced the serum iPTH level, which did not appear to be related to changes in serum Ca2+ because the Mg intake had no significant effect on serum levels of either total or ionized Ca2+. There was a strong positive correlation between serum iPTH and ionized Mg2+ (r = 0.699; P < 0.001), supporting the contention that decreased serum iPTH may be associated with the reduction in serum ionized Mg2+. Mg supplementation also reduced levels of both serum bone formation and resorption biochemical markers after 1-5 days, consistent with the premise that Mg supplementation may have a suppressive effect on bone turnover rate. Covariance analyses revealed that serum bone formation markers correlated negatively with ionized Mg2+ (r = -0.274 for type I procollagen peptide and -0.315 for osteocalcin), but not with iPTH or ionized Ca2+. Thus, the suppressive effect on bone formation may be mediated by the reduction in serum ionized Mg2+ level (and not iPTH or ionized Ca2+). In summary, this study has demonstrated for the first time that oral Mg supplementation in normal young adults caused reductions in serum levels of iPTH, ionized Mg2+, and biochemical markers of bone turnover. In conclusion, oral Mg supplementation may suppress bone turnover in young adults. Because increased bone turnover has been implicated as a significant etiological factor for bone loss, these findings raise the interesting possibility that oral Mg supplementation may have beneficial effects in reducing bone loss associated with high bone turnover, such as age-related osteoporosis.

Dimai HP, Porta S, Wirnsberger G, Lindschinger M…
J. Clin. Endocrinol. Metab. Aug 1998
PMID: 9709941

Magnesium Suppresses Bone Resorption Rats Fed a High-Phosphorus Diet

Abstract

Dietary magnesium supplementation suppresses bone resorption via inhibition of parathyroid hormone secretion in rats fed a high-phosphorus diet.

This study examined the effects of dietary magnesium (Mg) supplementation on bone turnover and serum parathyroid hormone (PTH) levels in rats fed a high-phosphorus (P) diet. Male rats were randomized by weight into three groups, and fed a control diet (control), a high-P diet (HP) or a high-P and high-Mg diet (HPHMg) for 14 days. Serum osteocalcin levels were significantly higher in the HP and HPHMg groups than in the control group. Serum CTx levels were significantly higher in the HP and HPHMg groups than in the control group, while the levels in the HPHMg group were significantly lower than in the HP group. Serum PTH levels were significantly higher in the HP group than in the control and HPHMg groups. Dietary Mg supplementation had a significant influence on serum PTH levels in the HP and HPHMg groups. These results suggest that dietary Mg supplementation suppresses the high bone resorption induced by a high-P diet via inhibition of PTH secretion. Moreover, our results suggest that dietary Mg supplementation may be beneficial for the prevention of bone loss with high-P diet administration.

Matsuzaki H, Fuchigami M, Miwa M
Magnes Res Sep 2010
PMID: 20810356 | Free Full Text