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Calorie Restriction Beneficial in Rats with High Oxidative Stress

Abstract

Effects of dietary restriction on total body, femoral, and vertebral bone in SENCAR, C57BL/6, and DBA/2 mice.

Dietary restriction (DR) increases the life span and retards aging, in part, by limiting free radical generation and oxidative damage. DR also reduces body mass, a major determinant of bone mass across the life span. We tested the hypothesis that DR has its most beneficial effects on bone in mouse strains with high free radical generation (sensitive to carcinogenesis [SENCAR] > C57 > DBA) versus the hypothesis that bone mass at weight-bearing sites is determined by body mass in DR and ad libitum (AL)-fed mice. Male mice of each strain were killed at 10 weeks of age (t(0)) or randomized to an AL-fed or 30% DR feeding regimen for 6 months. Food consumption by AL-fed mice was measured daily, and DR mice received 70% of the amount of food consumed by their respective AL-fed mice the previous day. Body fat (%) and bone mineral density (BMD) and content (BMC) were determined by PIXImus densitometry. There were strain-dependent effects on body mass, crown-to-rump length, percent body fat, and total body, femoral, and vertebral BMD and BMC under all conditions. SENCAR mice were heavier, longer, had larger bones, and generally exhibited higher total body, femoral, and vertebral BMC and BMD than C57 and DBA mice. DR had beneficial effects on BMD and BMC in the vertebrae of the SENCAR mouse model of high free radical generation and in the obese, diabetes-prone C57 mouse model of high end-stage protein glycation. DR DBA and SENCAR mice had lower femoral BMDs and BMCs than their respective AL-fed controls. Regression analysis confirmed linear relationships between total and lean body mass and total body and femoral BMDs and BMCs, suggesting that physiologic adaptation to a lower body mass accounts for the lower femoral bone mineral values observed in DR versus AL-fed mice. Thus, both hypotheses are, at least, partially valid. DR is beneficial in the trabeculae-rich vertebrae of animal models of high oxidant stress, and total/lean body mass determines BMD and BMC in the weight-bearing femur in DR and AL-fed mice.

Brochmann EJ, Duarte ME, Zaidi HA, Murray SS
Metab. Clin. Exp. Oct 2003
PMID: 14564677

Calcium + Magnesium From Seaweed Improves Bone More than Inorganic Calcium + Magnesium in Rats

Abstract

Magnesium supplementation through seaweed calcium extract rather than synthetic magnesium oxide improves femur bone mineral density and strength in ovariectomized rats.

Commercially available seaweed calcium extract can supply high amounts of calcium as well as significant amounts of magnesium and other microminerals. The purpose of this study was to investigate the degree to which the high levels of magnesium in seaweed calcium extract affects the calcium balance and the bone status in ovariectomized rats in comparison to rats supplemented with calcium carbonate and magnesium oxide. A total of 40 Sprague-Dawley female rats (7 weeks) were divided into four groups and bred for 12 weeks: sham-operated group (Sham), ovariectomized group (OVX), ovariectomized with inorganic calcium and magnesium supplementation group (OVX-Mg), and ovariectomized with seaweed calcium and magnesium supplementation group (OVX-SCa). All experimental diets contained 0.5% calcium. The magnesium content in the experimental diet was 0.05% of the diet in the Sham and OVX groups and 0.1% of the diet in the OVX-Mg and OVX-SCa groups. In the calcium balance study, the OVX-Mg and OVX-SCa groups were not significantly different in calcium absorption compared to the OVX group. However, the femoral bone mineral density and strength of the OVX-SCa group were higher than those of the OVX-Mg and OVX groups. Seaweed calcium with magnesium supplementation or magnesium supplementation alone did not affect the serum ALP and CTx levels in ovariectomized rats. In summary, consumption of seaweed calcium extract or inorganic calcium carbonate with magnesium oxide demonstrated the same degree of intestinal calcium absorption, but only the consumption of seaweed calcium extract resulted in increased femoral bone mineral density and strength in ovariectomized rats. Our results suggest that seaweed calcium extract is an effective calcium and magnesium source for improving bone health compared to synthetic calcium and magnesium supplementation.

Bae YJ, Bu SY, Kim JY, Yeon JY…
Biol Trace Elem Res Dec 2011
PMID: 21584658

Magnesium Deficiency Decreases Bone Density and Strength of Implants in Rats

Abstract

Effect of severe dietary magnesium deficiency on systemic bone density and removal torque of osseointegrated implants.

This study evaluated the effect of severe magnesium (Mg) dietary deficiency on systemic bone density and biomechanical resistance of bone tissue to the removal torque of osseointegrated implants.
The sample consisted of 45 rats; each received a titanium implant in their tibial metaphysis. After 60 days, the animals were divided into three groups (n = 15) according to their dietary Mg: the control group received the recommended content of Mg, group Mg1 received a 75% reduction in dietary Mg content, and group Mg2 was fed a diet with a 90% reduction in Mg content. Animals were sacrificed 150 days after implant placement. Serum concentrations of Mg were measured and the effect of Mg deficiency on systemic bone density was evaluated by densitometry of the lumbar vertebrae and femur. Biomechanical characteristics were measured by resistance of the bone tissue to removal of the implants. Results: Lower Mg serum concentrations were found for the Mg1 and Mg2 groups; however, densitometric analysis and torque evaluations showed a statistically significant difference only in the Mg2 group (P < .05). There was a statistically significant difference in removal torque between the Mg2 group and the control group.
This study showed that a severe deficiency of Mg decreased the systemic bone density and removal torque of osseointegrated implants.

Del Barrio RA, Giro G, Belluci MM, Pereira RM…
Int J Oral Maxillofac Implants
PMID: 21197488

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

Korean Black Raspberry Enhances Osteoblast Function In Vitro

Abstract

Rubus coreanus Miq. extract promotes osteoblast differentiation and inhibits bone-resorbing mediators in MC3T3-E1 cells.

To prevent bone loss that occurs with increasing age, certain nutritional and pharmacological factors are needed. In the present study, the ethanol extract from the fruit of Rubus coreanus Miq. (RCE) was investigated for its effect on the function of osteoblastic MC3T3-E1 cells. RCE (10approximately50 microg/ml) caused a significant elevation in cell viability, alkaline phosphatase (ALP) activity, collagen content, and osteocalcin secretion in the cells. The effect of RCE (50 microg/ml) in increasing cell viability, ALP activity, and collagen content was prevented by the presence of 10(-6) M cycloheximide and 10(-6) M tamoxifen, suggesting that RCE’s effect results from a newly synthesized protein component and might be partly involved in estrogen action. We then examined the effect of RCE on the H(2)O(2)-induced apoptosis and production of local factors in osteoblasts. Treatment with RCE (10approximately50 microg/ml) decreased the 0.2 mM H(2)O(2)-induced apoptosis and production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and nitric oxide (NO) in osteoblasts. Our data indicate that the enhancement of osteoblast function by Rubus coreanus Miq. may result in the prevention of osteoporosis and inflammatory bone diseases.

Lee KH, Choi EM
Am. J. Chin. Med. 2006
PMID: 16883635