Tag Archives: abstract

Lowering Sodium Increases the Effect of Calcium to Reduce Bone Loss in 124 Postmenopausal Women

Abstract

A longitudinal study of the effect of sodium and calcium intakes on regional bone density in postmenopausal women.

The influence of urinary sodium excretion and dietary calcium intake was examined in a 2-y longitudinal study of bone density in 124 women postmenopausal for > 10 y. Analysis of bone density changes showed that urinary sodium excretion was negatively correlated with changes in bone density at the intertrochanteric and total hip sites. Multiple-regression analysis of dietary calcium intake and urine sodium excretion on the change in bone density showed that both dietary calcium and urinary sodium excretion were significant determinants of the change in bone mass over 2 y at the hip and ankle sites. These data suggest that an effect of reducing bone loss equivalent to that achieved by a daily dietary increase of 891 mg (22 mmol) Ca can also be achieved by halving daily sodium excretion. No bone loss occurred at the total hip site at a calcium intake of 1768 mg/d (44 mmol/d) or a urine sodium excretion of 2110 mg/d (92 mmol/d). We report a significant effect of sodium excretion on bone loss in this population.

Devine A, Criddle RA, Dick IM, Kerr DA…
Am. J. Clin. Nutr. Oct 1995
PMID: 7572702 | Free Full Text

Risk Factors for Hip Fracture in 9,516 White Women

Abstract

Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group.

Many risk factors for hip fractures have been suggested but have not been evaluated in a comprehensive prospective study.
We assessed potential risk factors, including bone mass, in 9516 white women 65 years of age or older who had had no previous hip fracture. We then followed these women at 4-month intervals for an average of 4.1 years to determine the frequency of hip fracture. All reports of hip fractures were validated by review of x-ray films.
During the follow-up period, 192 women had first hip fractures not due to motor vehicle accidents. In multivariable age-adjusted analyses, a maternal history of hip fracture doubled the risk of hip fracture (relative risk, 2.0; 95 percent confidence interval, 1.4 to 2.9), and the increase in risk remained significant after adjustment for bone density. Women who had gained weight since the age of 25 had a lower risk. The risk was higher among women who had previous fractures of any type after the age of 50, were tall at the age of 25, rated their own health as fair or poor, had previous hyperthyroidism, had been treated with long-acting benzodiazepines or anticonvulsant drugs, ingested greater amounts of caffeine, or spent four hours a day or less on their feet. Examination findings associated with an increased risk included the inability to rise from a chair without using one’s arms, poor depth perception, poor contrast sensitivity, and tachycardia at rest. Low calcaneal bone density was also an independent risk factor. The incidence of hip fracture ranged from 1.1 (95 percent confidence interval, 0.5 to 1.6) per 1,000 woman-years among women with no more than two risk factors and normal calcaneal bone density for their age to 27 (95 percent confidence interval, 20 to 34) per 1,000 woman-years among those with five or more risk factors and bone density in the lowest third for their age.
Women with multiple risk factors and low bone density have an especially high risk of hip fracture. Maintaining body weight, walking for exercise, avoiding long-acting benzodiazepines, minimizing caffeine intake, and treating impaired visual function are among the steps that may decrease the risk.

Cummings SR, Nevitt MC, Browner WS, Stone K…
N. Engl. J. Med. Mar 1995
PMID: 7862179 | Free Full Text

Fish Oil Reduces Bone Resorption in Postmenopausal Women Taking Aromatase Inhibitors

Abstract

High-dose eicosapentaenoic acid and docosahexaenoic acid supplementation reduces bone resorption in postmenopausal breast cancer survivors on aromatase inhibitors: a pilot study.

Postmenopausal breast cancer survivors are living longer; however, a common class of drugs, aromatase inhibitors (AI), depletes estrogen levels, promotes bone loss, and heightens fracture risk. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may offset AI effects to bone because of the known effects on cellular processes of bone turnover. Therefore, we hypothesized that 4 g of EPA and DHA daily for 3 mo would decrease bone turnover in postmenopausal breast cancer survivors on AI therapy in a randomized, double-blind, placebo controlled pilot study that included 38 women. At baseline and 3 mo, serum fatty acids, bone turnover, and inflammatory markers were analyzed. Serum EPA and DHA, total and long-chain (LC) omega (n)-3 polyunsaturated fatty acids (PUFA) increased, whereas arachidonic acid, total and LC n-6 PUFA, and the LC n-6:n-3 PUFA ratio decreased compared to placebo (all P < .05). Bone resorption was inhibited in the fish oil responders compared to placebo (P < .05). Inflammatory markers were not altered. This short-term, high-dose fish oil supplementation study’s findings demonstrate that fish oil can reduce bone resorption; however, longer-term studies are needed to assess bone density preservation and to explore mechanistic pathways in this population at high risk for bone loss.

Hutchins-Wiese HL, Picho K, Watkins BA, Li Y…
Nutr Cancer 2014
PMID: 24274259

Fish Oil Benefits Bone in Salt-Loaded Rats

Abstract

Benefits of omega-3 fatty acid against bone changes in salt-loaded rats: possible role of kidney.

There is evidence that dietary fats are important components contributing in bone health and that bone mineral density is inversely related to sodium intake. Salt loading is also known to impose negative effects on renal function. The present study aimed to determine the effect of the polyunsaturated fatty acid omega-3 on bone changes imposed by salt loading, highlighting the role of kidney as a potential mechanism involved in this effect. Male Wistar rats were divided into three groups: control group, salt-loaded group consuming 2% NaCl solution as drinking water for 8 weeks, and omega-3-treated salt-loaded group receiving 1 g/kg/day omega-3 by gavage with consumption of 2% NaCl solution for 8 weeks. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) were recorded. Plasma levels of sodium, potassium, calcium, inorganic phosphorus (Pi), alkaline phosphatase (ALP), creatinine, urea, 1,25-dihydroxyvitamin D [1,25(OH)2D3], and transforming growth factor-beta1 (TGF-β1) were measured. The right tibia and kidney were removed for histologic examination and renal immunohistochemical analysis for endothelial nitric oxide synthase (eNOS) was performed. The results revealed that omega-3 reduced SBP, DBP, and MAP and plasma levels of sodium, potassium, Pi, creatinine, urea, and TGF-β1, but increased plasma levels of calcium, ALP, and 1,25(OH)2D3 as well as renal eNOS. Omega-3 increased cortical and trabecular bone thickness, decreased osteoclast number, and increased newly formed osteoid bone. Renal morphology was found preserved. In conclusion, omega-3 prevents the disturbed bone status imposed by salt loading. This osteoprotective effect is possibly mediated by attenuation of alterations in Ca(2+), Pi, and ALP, and improvement of renal function and arterial blood pressure.

Ahmed MA, Abd El Samad AA
Physiol Rep Oct 2013
PMID: 24303178 | Free Full Text

The acquisition and maintenance of bone mass and strength are influenced by environmental factors, including physical activity and nutrition (Massey and Whiting 1996). Nutrition is important to bone health, and a number of minerals and vitamins have been identified as playing a potential role in the prevention of bone diseases, particularly osteoporosis (Massey and Whiting 1996). Evidence indicates that dietary fats can influence bone health (Tartibian et al. 2010), in particular the omega-3 (n-3) polyunsaturated fatty acids (PUFAs), as they have been shown to inhibit osteoclast activity and enhance osteoblast activity (Watkins et al. 2003). Eicosapentaenoic acid (EPA) supplementation was found to increase bone mineral density in postmenopausal women (Terano 2001). Beneficial effects of n-3 PUFAs on markers of bone resorption and formation in animal (Shen et al. 2006) and human (Griel et al. 2007) studies have, also, been observed.

On the other hand, a number of studies suggested a detrimental effect of dietary salt on bone. Devine et al. (1995) showed that change in bone mineral density was inversely related to sodium intake and that both dietary calcium and urinary sodium excretion were significant determinants of the change in bone mass. High-sodium diet was found to increase urinary calcium excretion and cause loss of bone calcium (Chan and Swaminathan 1998), while reducing sodium intake complemented the beneficial skeletal effects of the Dietary Approaches to Stop Hypertension diet (Lin et al. 2003). Furthermore, an epidemiological study of men and women has shown that salt intake is associated with markers of bone resorption and appears likely to be a risk factor for osteoporosis (Jones et al. 1997). Similar effect of sodium loading has been demonstrated in animal model (Gold and Gouldin 1995).

 

Review: Inadequate Protein is a Greater Problem for Bone Health Than Protein Excess

Abstract

Does a high dietary acid content cause bone loss, and can bone loss be prevented with an alkaline diet?

A popular concept in nutrition and lay literature is that of the role of a diet high in acid or protein in the pathogenesis of osteoporosis. A diet rich in fruit and vegetable intake is thought to enhance bone health as the result of its greater potassium and lower “acidic” content than a diet rich in animal protein and sodium. Consequently, there have been a number of studies of diet manipulation to enhance potassium and “alkaline” content of the diet to improve bone density or other parameters of bone health. Although acid loading or an acidic diet featuring a high protein intake may be associated with an increase in calciuria, the evidence supporting a role of these variables in the development of osteoporosis is not consistent. Similarly, intervention studies with a more alkaline diet or use of supplements of potassium citrate or bicarbonate have not consistently shown a bone health benefit. In the elderly, inadequate protein intake is a greater problem for bone health than protein excess.

Hanley DA, Whiting SJ
J Clin Densitom. Oct 2013
PMID: 24094472

Review: Protein and Bone Studies

Abstract

Health effects of protein intake in healthy adults: a systematic literature review.

The purpose of this systematic review is to assess the evidence behind the dietary requirement of protein and to assess the health effects of varying protein intake in healthy adults. The literature search covered the years 2000-2011. Prospective cohort, case-control, and intervention studies were included. Out of a total of 5,718 abstracts, 412 full papers were identified as potentially relevant, and after careful scrutiny, 64 papers were quality graded as A (highest), B, or C. The grade of evidence was classified as convincing, probable, suggestive or inconclusive. The evidence is assessed as: probable for an estimated average requirement of 0.66 g good-quality protein/kg body weight (BW)/day based on nitrogen balance studies, suggestive for a relationship between increased all-cause mortality risk and long-term low-carbohydrate-high-protein (LCHP) diets; but inconclusive for a relationship between all-cause mortality risk and protein intake per se; suggestive for an inverse relationship between cardiovascular mortality and vegetable protein intake; inconclusive for relationships between cancer mortality and cancer diseases, respectively, and protein intake; inconclusive for a relationship between cardiovascular diseases and total protein intake; suggestive for an inverse relationship between blood pressure (BP) and vegetable protein; probable to convincing for an inverse relationship between soya protein intake and LDL cholesterol; inconclusive for a relationship between protein intake and bone health, energy intake, BW control, body composition, renal function, and risk of kidney stones, respectively; suggestive for a relationship between increased risk of type 2 diabetes (T2D) and long-term LCHP-high-fat diets; inconclusive for impact of physical training on protein requirement; and suggestive for effect of physical training on whole-body protein retention. In conclusion, the evidence is assessed as probable regarding the estimated requirement based on nitrogen balance studies, and suggestive to inconclusive for protein intake and mortality and morbidity. Vegetable protein intake was associated with decreased risk in many studies. Potentially adverse effects of a protein intake exceeding 20-23 E% remain to be investigated.

Pedersen AN, Kondrup J, Børsheim E
Food Nutr Res 2013
PMID: 23908602 | Free Full Text

Based on a validated FFQ, a French study of postmenopausal women with a habitual HP intake (45), there was no overall association between fracture risk and total protein intake. In the presence of low calcium intake (<400 mg/1,000 kcal), there was an increased risk of fractures related to energy-adjusted total and animal protein as well as gram per kg BW, while energy-adjusted vegetable protein was associated with a decreased fracture risk. In the Framingham Offspring Study of men and women (46), there was no overall association between fracture risk and total protein intake based on FFQ. Animal protein intake was associated with an increased fracture risk provided a low (<800 mg) calcium intake and a decreased risk of fractures provided a high (>800 mg) calcium intake. The Study of Osteoporotic Fractures in postmenopausal women (42) found increased risk of hip fractures related to high animal protein intake and high A/V ratio estimated from FFQ. When the model was adjusted for BMD, the relation of A/V ratio to fracture risk became non-significant. The systematic review and meta-analysis (44) found no relationship between protein intake and risk of fractures, neither in the cohort studies nor in the supplemental studies.

[…]

A systematic review and meta-analysis assessed the relation of dietary acid load to bone health (47), quality graded as C because of the lack of information about dietary intake methods or intervention (see Appendix C, Table C10). The analysis did not support the hypothesis that ‘acid’ from the diet causes osteoporosis or that an ‘alkaline’ diet prevents osteoporosis. The systematic review also indicated that higher protein intake and animal protein were not detrimental to calcium retention. The ideal protein intake for bone health could not be determined.

[…]

Two intervention trials including postmenopausal women (48, 49), quality graded as B and A, respectively, were identified for the association between protein and calcium and bone metabolism (see Appendix C, Table C10). Harrington et al. (48) used a high-sodium–high-protein diet versus a low-sodium–UP diet in a randomized cross-over trial. Thus, it was difficult to separate the effect of protein per se. Nevertheless, they found that a high-sodium HP diet led to increased urinary calcium loss and increased bone resorption. In a high-quality feeding trial by Hunt et al. (49), high- (20 E%) or low- (10 E%) protein intake was combined with high- (1,510 mg) and low-calcium (675 mg) intake in a randomized four interventions’ cross-over design. They found that the combination of HP and low-calcium diet increased calcium retention, and it also resulted in an increase in IGF-1, an anabolic peptide hormone stimulating bone formation.

Protodioscin Inhibits Bone Loss in Ovariectomized Rats

Abstract

In vivo antiosteoporotic activity of a fraction of Dioscorea spongiosa and its constituent, 22-O-methylprotodioscin.

The antiosteoporotic activity of the 90 % EtOH fraction of the water extract of rhizomes of Dioscorea spongiosa and methylprotodioscin, its major constituent, were examined in the model of postmenopausal bone loss using ovariectomized (OVX) rats or mice. After 6 weeks treatment, the proximal tibia of rats or mice and the distal femora of mice were scanned by peripheral quantitative computed tomography (pQCT). Both the 90 % EtOH fraction (100 mg/kg/d) and methylprotodioscin (50 mg/kg/d) significantly inhibited bone loss in bone mineral content (BMC) and bone mineral density (BMD) in total, cancellous and cortical bones, and the decrease in bone strength indexes induced by OVX, without side effect on the uterus.

Yin J, Tezuka Y, Kouda K, Le Tran Q…
Planta Med. Mar 2004
PMID: 15114498

Silibinin Promotes Osteoblasts In Vitro

Abstract

Silibinin promotes osteoblast differentiation of human bone marrow stromal cells via bone morphogenetic protein signaling.

Silibinin is the major active constituent of the natural compound silymarin; several studies suggest that silibinin possesses antihepatotoxic properties and anticancer effects against carcinoma cells. However, no study has yet investigated the effect of silibinin on osteogenic differentiation of human bone marrow stem cells (hBMSCs). The aim of this study was to evaluate the effect of silibinin on osteogenic differentiation of hBMSCs. In this study, the hBMSCs were cultured in an osteogenic medium with 0, 1, 10 or 20 μmol/l silibinin respectively. hBMSCs viability was analyzed by cell number quantification assay and cells osteogenic differentiation was evaluated by alkaline phosphatas (ALP) activity assay, Von Kossa staining and real time-polymerase chain reaction (RT-PCR). We found that silibinin promoted ALP activity in hBMSCs without affecting their proliferation. The mineralization of hBMSCs was enhanced by treatment with silibinin. Silibinin also increased the mRNA expressions of Collagen type I (COL-I), ALP, Osteocalcin (OCN), Osterix, bone morphogenetic protein-2 (BMP-2) and Runt-related transcription factor 2 (RUNX2). The BMP antagonist noggin and its receptor kinase inhibitors dorsomorphin and LDN-193189 attenuated silibinin-promoted ALP activity. Furthermore, BMP-responsive and Runx2-responsive reporters were activated by silibinin treatment. These results indicate that silibinin enhances osteoblast differentiation probably by inducing the expressions of BMPs and activating BMP and RUNX2 pathways. Thus, silibinin may play an important therapeutic role in osteoporosis patients by improving osteogenic differentiation of BMSCs.

Ying X, Sun L, Chen X, Xu H…
Eur. J. Pharmacol. Dec 2013
PMID: 24076187

Calcium Threonate in Ester-C Enhances Vitamin C’s Bone Mineralization In Vitro

Abstract

Enhanced production of mineralized nodules and collagenous proteins in vitro by calcium ascorbate supplemented with vitamin C metabolites.

Vitamin C or ascorbate is important in wound healing due to its essential role in collagen synthesis. To study wound healing in the periodontium, cells adherent to expanded polytetrafluoroethylene (ePTFE) augmentation membranes, recovered from edentulous ridge augmentation procedures, have been established in culture in our laboratories. The objective of this study was to determine whether treatment of these cells with a calcium ascorbate, which contains vitamin C metabolites (metabolite-supplemented ascorbate), would increase the production of collagenous protein and mineralized tissue in vitro, as compared to unsupplemented calcium ascorbate (ascorbate).
Cells derived from ePTFE membranes were cultured with beta-glycerophosphate and the test agents for 2 to 5 weeks, and the surface areas of the cell cultures occupied by mineralized nodules were measured using computerized image analysis. One experiment tested the effects of calcium threonate, one of the vitamin C metabolites in metabolite-supplemented ascorbate. Incorporation of radioactive proline and glycine was used as a measure of total protein (radioactivity precipitated by trichloracetic acid) and collagenase-digestible protein (radioactivity released by collagenase digestion.) Co-localization of collagen and fibronectin was examined by immunofluorescence.
In vitro treatment of these cells with metabolite-supplemented ascorbate increased the area of the cell cultures occupied by mineralized nodules after 5 weeks. Cell cultures treated with metabolite-supplemented ascorbate also exhibited significant increases in total protein. The increase in collagenous proteins in these cultures accounted for 85% of the increase in total protein. The greatest difference between treatment groups was observed in the cell-associated fraction containing the extracellular matrix. The additional collagen exhibited normal co-distribution with fibronectin. In cultures treated with ascorbate spiked with calcium threonate, the area of mineralized tissue was significantly greater than in ascorbate-treated cultures, but was less than that observed in cultures treated with metabolite-supplemented ascorbate.
In vitro treatment with ascorbate containing vitamin C metabolites enhanced the formation of mineralized nodules and collagenous proteins. Calcium threonate may be one of the metabolites influencing the mineralization process. Identifying factors which facilitate the formation of mineralized tissue has significant clinical ramifications in terms of wound healing and bone regeneration.

Rowe DJ, Ko S, Tom XM, Silverstein SJ…
J. Periodontol. Sep 1999
PMID: 10505801

This study is on Ester-C. Ester-C, PureWay-C, and AlphaSorb-C are Vitamin C products that contain Calcium-L-Threonate. Biocalth is Calcium product which is all Calcium-L-Threonate without Vitamin C.

 

L-Threonate Inhibits Resorption In Vitro

Abstract

[Effects of L-threonate on bone resorption by osteoclasts in vitro].

To clarify if calcium L-threonate and sodium L-threonate have inhibitory effects on the bone resorption of rabbit’s osteoclasts in vitro.
This study contained a total of 16 culture groups, including one group as control and 5 groups treated by 5 drugs (calcium D-threonate, sodium L-threonate, alendronate, 17beta-estradiol and calcium gluconate) each at the final concentrations of 10(-9) mol/L, 10(-7) mol/L, 10(-5) mol/L respectively. After 7 days, eight bone slices of every group were stained with toluidine blue and the areas of resorptive pits were analyzed under light microscope; the concentrations of C-telopeptide of type I collagen (CTx or Crosslaps) in culture supernatants were measured by ELISA.
(1) The resorption area and the CTx concentration of the Calcium L-threonate groups were reduced significantly as compared with those of control and of Calcium gluconate groups respectively. The resorption area and CTx level of the Sodium L-threonate groups were significantly reduced when compared with those of the control, but the effects of Calcium gluconate groups were not so. (2) The reduction in the resorption area and CTx concentration of Calcium L-threonate group was more than that of Sodium L-threonate group. (3) The reductive effect of the high concentration (10(-5)) group of Calcium L-threonate on the area and CTx level was corresponding to that of 17beta-estradiol at a concentration between 10(-7) and 10(-9). (4) The resorption area was related to the CTx concentration (r=0.876). (5) The CTX level was much more sensitive, precise and stable than the concentration.
L-threonate, especially calcium L-threonate could inhibit the bone resorption of osteoclasts in vitro, and its effect might be related to the radical of L-threonic acid. The CTx concentration in culture supernatants might be an effective marker quantitatively reflecting the bone resorption by osteoclasts in vitro.

He JH, Tong NW, Li HQ, Wu J
Sichuan Da Xue Xue Bao Yi Xue Ban Mar 2005
PMID: 15807273