Monthly Archives: March 2014

Magnesium Water No Benefit in Postmenopausal Women

Abstract

A double-blind, placebo-controlled study of the short term effects of a spring water supplemented with magnesium bicarbonate on acid/base balance, bone metabolism and cardiovascular risk factors in postmenopausal women.

A number of health benefits including improvements in acid/base balance, bone metabolism, and cardiovascular risk factors have been attributed to the intake of magnesium rich alkaline mineral water. This study was designed to investigate the effects of the regular consumption of magnesium bicarbonate supplemented spring water on pH, biochemical parameters of bone metabolism, lipid profile and blood pressure in postmenopausal women. In this double-blind, placebo-controlled, parallel-group, study, 67 postmenopausal women were randomised to receive between 1500 mL and 1800 mL daily of magnesium bicarbonate supplemented spring water (650 mg/L bicarbonate, 120 mg/L magnesium, pH 8.3-8.5) (supplemented water group) or spring water without supplements (control water group) over 84 days. Over this period biomarkers of bone turnover (serum parathyroid hormone (PTH), 1,25-dihydroxyvitamin D, osteocalcin, urinary telopeptides and hydroxyproline), serum lipids (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides), venous and urinary pH were measured together with measurements of standard biochemistry, haematology and urine examinations. Serum magnesium concentrations and urinary pH in subjects consuming the magnesium bicarbonate supplemented water increased significantly at Day 84 compared to subjects consuming the spring water control (magnesium – p = 0.03; pH – p = 0.018). The consumption of spring water led to a trend for an increase in parathyroid hormone (PTH) concentrations while the PTH concentrations remained stable with the intake of the supplemented spring water. However there were no significant effects of magnesium bicarbonate supplementation in changes to biomarkers of bone mineral metabolism (n-telopeptides, hydroxyproline, osteocalcin and 1,25-dihydroxyvitamin D) or serum lipids or blood pressure in postmenopausal women from Day 0 to Day 84.
Short term regular ingestion of magnesium bicarbonate supplemented water provides a source of orally available magnesium. Long term clinical studies are required to investigate any health benefits.

Day RO, Liauw W, Tozer LM, McElduff P…
BMC Res Notes 2010
PMID: 20579398 | Free Full Text

The acid/base theory is questionable and this was a low dose of Magnesium.

Review: Vitamin A Increases Fracture Risk at 2x Recommended Intake

Abstract

Vitamin A intake and osteoporosis: a clinical review.

If osteoporosis is linked with vitamin A (Vit A) A consumption, millions of people could be affected. A MEDLINE search was performed with keywords retinol, beta-carotene, and osteoporosis. Of 20 clinical studies, 3 were randomized controlled trials (RCTs), 14 were observational studies, and 3 were case reports. Most (8) observational studies were cross-sectional. Oral retinoyl palmitate (RP) in high doses induces fractures and radiographic osteoporosis in animals. Retinol intake from diet or supplements is negatively associated with lumbar, femoral neck, and trochanter bone mineral density (BMD). There is a graded increase in relative risk of hip fracture with increasing retinol intake, attributable primarily to retinol (either from diet or supplements) but not beta-carotene intake. Higher serum retinol levels are associated with higher risk of any fracture and with higher risk of hip fracture, whereas there is no evidence of harm associated with beta-carotene intake. The few RCTs involve serum markers of bone metabolism, not bone density or fracture outcomes. Observational studies are generally consistent in finding harm from either dietary or supplemental retinol intake on BMD and hip fracture risk. Total Vit A intake is more important than source in determining harm. Adverse effects may occur at a level of retinol intake that is only about twice the current recommendation for adult females.
It is not yet possible to set a specific level of retinol intake above which bone health is compromised. Pending further investigation, Vit A supplements should not be used with the express goal of improving bone health.

Crandall C
J Womens Health (Larchmt) Oct 2004
PMID: 15671709

The recommended dietary allowance (RDA) for Vitamin as preformed Vitamin A (Retinol Activity Equivalents) is 700 mcg (or 2,333 IU). This article suggests that twice that, or 4666 IU, increases fracture risk.

Vitamin A Not Associated with Bone Density or Fracture in 2016 Perimenopausal Danish Women

Abstract

No effect of vitamin A intake on bone mineral density and fracture risk in perimenopausal women.

In recent studies from Sweden and the United States, a high vitamin A intake has been associated with low bone mineral density (BMD) and increased fracture risk. In Sweden and the United States, food items such as milk and breakfast cereals are fortified with vitamin A, whereas in Denmark there is no mandatory fortification with vitamin A. In the present study, we investigated relations between vitamin A intake and BMD and fracture risk in a Danish population consuming mostly unfortified food items. Within a population-based cohort study in 2,016 perimenopausal women, associations between BMD and vitamin A intake were assessed at baseline and after 5-year follow-up. Moreover, associations between baseline vitamin A intake and 5-year changes in BMD were studied. Finally, fracture risk was assessed in relation to vitamin A intake. In our cohort, dietary retinol intake (0.53 mg/day) was lower than the intake reported in recent studies form Sweden (0.78 mg/day) and the United States (1.66 mg/day). Cross-sectional and longitudinal analyses showed no associations between intake of vitamin A and BMD of the femoral neck or lumbar spine. Neither did BMD differ between those 5% who had the highest, and those 5% who had the lowest, vitamin A intake. During the 5-year study period, 163 subjects sustained a fracture (cases). Compared to 978 controls, logistic regression analyses revealed no difference in vitamin A intake. Thus, in a Danish population, average vitamin A intake is lower than in Sweden and the United States and not associated with detrimental effects on bone.

Rejnmark L, Vestergaard P, Charles P, Hermann AP…
Osteoporos Int Nov 2004
PMID: 15034644

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

Korean Black Raspberry Increases Osteoblasts and Apoptosis of Osteoclasts in Ovariectomized Rats

Abstract

Bone-protecting effect of Rubus coreanus by dual regulation of osteoblasts and osteoclasts.

Bone loss occurs with increasing age and/or as a secondary occurrence to chronic metabolic disease. Certain nutritional and pharmacological, as well as nonpharmacologic interventions such as weight-bearing exercise and muscle strengthening help prevent bone loss. We examined the effect of the methanol extract from the fruit of Rubus coreanus (RCM) on postmenopausal osteoporosis.
Ovariectomized rats were assigned to sham (negative control), vehicle control, positive control, safflower seed 200 mg/kg, RCM 100 mg/kg (RCM 100), RCM 200 mg/kg (RCM 200), and RCM 400 mg/kg (RCM 400) groups for 10 weeks after the operation. Serum biochemistry, histochemistry, immunohistochemistry, and other related biomarkers of bone metabolism were investigated.
We observed that RCM could prevent bone loss by increasing the femur trabecular bone area in a dose-dependent manner in ovariectomized rats. The mineral composition of RCM contains many more valuable elements, especially potassium, magnesium, and vitamins D and B2, than safflower seed. The effect of RCM increased not only osteoblast differentiation but also osteoclast apoptosis. In addition, the extract of RCM contained in quercetin suggests that the extract of RCM resulted in improved aging-related bone loss through an antioxidant effect.
The present data provide the first direct in vivo evidence that RCM has a bone-protecting effect caused by estrogen deficiency, without undesirable side effects on the uterus and other solid organs. The beneficial effect of RCM may be mediated, at least in part, by dual regulation of the enhancement of osteoblast function and induction of osteoclast apoptosis.

Do SH, Lee JW, Jeong WI, Chung JY…
Menopause
PMID: 18709701

Sodium Associated with Higher Bone Density

Abstract

Dietary sodium and bone mineral density: results of a 16-year follow-up study.

It has been proposed that high dietary sodium intake, resulting in a sodium-mediated increase in renal calcium excretion, is a risk factor for osteoporosis. To evaluate the relationship between dietary sodium intake and bone mineral density (BMD), a prospective study of the Rancho Bernardo cohort was performed. A 24-hour diet recall was done for the period 1973 through 1975; follow-up bone mineral density of the ultradistal radius, midradius, total hip, and spine was measured between 1988 and 1991. Covariates were ascertained by self-report and examination at baseline. Multivariable analysis of the sodium-BMD association was performed using gender and menopause-specific linear regressions.
All subjects were white. At the bone evaluation, there were 258 women (average age 73.3 years) and 169 men (average age 72.4 years). In both men and women, higher levels of sodium intake were strongly associated with higher levels of calcium intake and total calories. Body mass index increased with sodium quartile in women, while a modest negative association was seen in men. In women, after age adjustment, positive associations between dietary sodium and bone density were found at the ultradistal radius (beta = 0.01, P = 0.03) and the total hip (beta = 0.019, P = 0.02). BMD increased by 0.01 to 0.02 g/cm2 per gram increase in sodium ingested. After adjustment for estrogen use, body mass, dietary calcium, alcohol, and total calories, these effects were no longer significant. Similar patterns were seen in pre- and postmenopausal women. In men, age and multivariate-adjusted BMD increased with higher sodium intake at the ultradistal radius only (beta = 0.013, P = 0.05). Stratification by gender-specific median calcium level did not significantly effect the results.
After control for confounders, a small, statistically significant protective effect of sodium was found at the ultradistal radius in men only. At other sites in women and men, no effect of sodium on BMD was apparent in the multivariable models. These results do not support a detrimental effect of dietary sodium on bone mineral density. Rather, the findings suggest that sodium intake, in the range measured, is not a major osteoporosis risk factor.

Greendale GA, Barrett-Connor E, Edelstein S, Ingles S…
J Am Geriatr Soc Oct 1994
PMID: 7930328

Review: Optimal Treatment may Include Both Anabolic and Antiresorptive Treatments

Abstract

Future directions in osteoporosis therapeutics.

Future directions in osteoporosis treatment will include development of medications with increasingly precise mechanistic targets, including the RANK-ligand pathway, cathepsin K inhibition, and Wnt signaling manipulation. More gains are likely with anabolics and newer antiresorptives that cause little or no suppression of formation. Optimal treatment of osteoporosis may require coordination of anabolic and antiresorptive treatment, following stimulation of bone formation with consolidation and long-term maintenance. Some well-established drugs may be useful in such regimens. We can also anticipate emphasis on cost containment using currently available drugs, especially as they become generic. Effective implementation and treatment continuity will be important themes.

Bone H
Endocrinol. Metab. Clin. North Am. Sep 2012
PMID: 22877435

Oligogalacturonic Acid Inhibits Resorption In Vitro

Abstract

Oligogalacturonic acid inhibit bone resorption and collagen degradation through its interaction with type I collagen.

In this study, we showed that oligogalacturonic acid (OGA) purified from flax pectin inhibit in vitro osteoclastic bone resorption in a dose-dependent manner. The OGA inhibitory effect was neither linked to an effect on osteoclast apoptosis, nor to an inhibition of cathepsin K activity. By means of an in vitro collagen degradation assay we demonstrated that OGA prevented triple-helical type I collagen cleavage by cathepsin K in a dose and chain length dependent manner. This inhibition was not restricted to cathepsin K, since collagenolytic activity of other lysosomal cysteine proteases, such as cathepsin B and cathepsin L, as well as matrixmetalloproteinases such as MMP-9 were also inhibited. Interestingly, using non-collagen substrates we demonstrated that OGA does not inhibit the proteolytic activity of cathepsin B and L, suggesting that OGA inhibits collagen degradation without affecting the lysosomal cysteine enzyme proteolytic activity. Finally, preliminary study using surface plasmon resonance (SPR) showed that OGA binds to type I collagen but not to albumin, consistent with a specific effect on collagen. These results suggest that the observed inhibition of collagen degradation by OGA may be due to its ability to bind to the collagen molecule. By masking the collagen surface, OGA may render the collagen cleavage site less accessible to enzymes and thus prevent its enzymatic degradation.

Lion JM, Mentaverri R, Rossard S, Jullian N…
Biochem. Pharmacol. Dec 2009
PMID: 19647720

Resistive Vibration Exercise May Reduce Bone Loss During Bed Rest in Men

Abstract

Resistive vibration exercise attenuates bone and muscle atrophy in 56 days of bed rest: biochemical markers of bone metabolism.

During and after prolonged bed rest, changes in bone metabolic markers occur within 3 days. Resistive vibration exercise during bed rest impedes bone loss and restricts increases in bone resorption markers whilst increasing bone formation. To investigate the effectiveness of a resistive vibration exercise (RVE) countermeasure during prolonged bed rest using serum markers of bone metabolism and whole-body dual X-ray absorptiometry (DXA) as endpoints.
Twenty healthy male subjects underwent 8 weeks of bed rest with 12 months follow-up. Ten subjects performed RVE. Blood drawings and DXA measures were conducted regularly during and after bed rest.
Bone resorption increased in the CTRL group with a less severe increase in the RVE group (p = 0.0004). Bone formation markers increased in the RVE group but decreased marginally in the CTRL group (p < 0.0001). At the end of bed rest, the CTRL group showed significant loss in leg bone mass (-1.8(0.9)%, p = 0.042) whereas the RVE group did not (-0.7(0.8)%, p = 0.405) although the difference between the groups was not significant (p = 0.12).
The results suggest the countermeasure restricts increases in bone resorption, increased bone formation, and reduced bone loss during bed rest.

Armbrecht G, Belavý DL, Gast U, Bongrazio M…
Osteoporos Int Apr 2010
PMID: 19536451

Judo Provides Powerful Oseogenic Stimuli Despite Off-Season Weight Loss

Abstract

Bone density in elite judoists and effects of weight cycling on bone metabolic balance.

Weight cycling has been shown to exert negative effects on bone metabolism and bone mass, whereas weight-bearing activity is positively associated with bone mineral density (BMD). Bone health in judoists and effects of weight cycling on bone metabolism have not previously been investigated. To examine potential disrupter and stimulators of bone integrity, this study analyzed bone parameters at baseline and the effects of the first weight cycle of the season on bone metabolic status in 48 male and female elite judoists.
Body composition and lumbar, femoral, and total body BMD were evaluated by dual-energy x-ray absorptiometry. Cortisol, osteocalcin, C-terminal telopeptide of type I collagen (CTx), and bone uncoupling index (UI) were measured in judoists at normal body weight, after weight reduction, and after regaining weight. As a comparison, a control group of moderately active students was included at baseline. Training, menstrual status, and calcium intake were assessed by questionnaires.
Euweighted judoists displayed high BMD and an increased rate of bone formation. Precompetitive weight loss averaged 4 +/- 0.3% of body weight and induced an acute rise in cortisol (81%, P < 0.05) and CTx (33%, P < 0.0001), with a metabolic imbalance in favor of bone resorption. A 4 +/- 0.5% weight regain restored a positive UI in favor of bone formation. Metabolic responses were not dependent on gender. BMD was unaltered by weight cycling.
Increased bone formation rate pertaining to judo athletes lent protection from alterations in bone metabolic balance associated with weight cycling. This observation suggests that powerful osteogenic stimuli provided by judo’s unique biomechanical environment may help prevent bone loss associated with weight loss.

Prouteau S, Pelle A, Collomp K, Benhamou L…
Med Sci Sports Exerc Apr 2006
PMID: 16679985