Monthly Archives: April 2014

Curcumol Suppresses Osteoclast Formation In Vitro

Abstract

Curcumol suppresses RANKL-induced osteoclast formation by attenuating the JNK signaling pathway.

Osteoclasts, derived from hemopoietic progenitors of the monocyte/macrophage lineage, have a unique role in bone resorption, and are considered a potential therapeutic target in the treatment of such pathologic bone diseases as osteoporosis, rheumatoid arthritis, and periodontitis. In the present study, we demonstrate that curcumol, one of the major components of the essential oil of Rhizoma Curcumae, exhibits an inhibitory effect on receptor activator of nuclear factor kappaB ligand (RANKL)-induced osteoclast differentiation with both bone marrow-derived macrophages and RAW264.7 cells in a dose-dependent manner. In addition, RANKL-induced mRNA expression of osteoclast-specific genes, such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K, is prominently reduced in the presence of curcumol. Furthermore, the molecular mechanism of action was investigated, and curcumol inhibited osteoclastogenesis by specifically impairing RANKL-induced c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) signaling, which was further identified in rescue studies by means of anisomycin, a JNK signaling-specific activator. Taken together, these findings suggest that curcumol suppresses RANKL-induced osteoclast differentiation through the JNK/AP-1 signaling pathway, and may be useful as a therapeutic treatment for bone resorption-associated diseases.

Yu M, Chen X, Lv C, Yi X…
Biochem. Biophys. Res. Commun. Apr 2014
PMID: 24732351

Vitamin E Associated with Increased Bone Density in Postmenopausal Women

Abstract

Lower vitamin E serum levels are associated with osteoporosis in early postmenopausal women: a cross-sectional study.

The aim of this study was to evaluate the relationship between vitamin E status and osteoporosis in early postmenopausal women. Anthropometric data, osteoporosis risk factors, vitamin E serum levels, bone mineral density (BMD) and other serum parameters which may influence bone mineral density in postmenopausal women were analyzed in a cross-sectional study. The association between osteoporosis and age, age of menopause, body mass index, osteocalcin, calcium, vitamin D, vitamin E (measured as 25 hydroxyvitamin D and as α-tocopherol:lipids ratio, respectively), bone alkaline phosphatase, smoking status, leisure physical activity and alcohol intake were modeled by a multivariate logistic regression and multi-linear regression analysis in 232 early postmenopausal women. A lower vitamin E:lipid ratio was associated with osteoporosis in multivariate logistic regression. In a multivariate linear model with BMD of the lumbar spine as a dependent variable, the vitamin E:lipid ratio was clearly related with BMD of the lumbar spine (F ratio = 6.30, p = 0.002). BMD of the lumbar spine was significantly higher in the highest tertile of the vitamin E:lipid ratio than in the lowest tertile. The mean vitamin E:lipid ratio was significantly lower in osteoporotic postmenopausal women (T score ≤-2.5) (3.0 ± 0.6 μmol/mmol) than normal (neither osteoporotic nor osteopenic) postmenopausal women (T score >-1) (3.5 ± 0.7 μmol/mmol) using multivariable-adjusted BMD. These findings highlight that vitamin E may increase BMD in healthy postmenopausal women.

Mata-Granados JM, Cuenca-Acebedo R, Luque de Castro MD, Quesada Gómez JM
J. Bone Miner. Metab. Jul 2013
PMID: 23536191

Review: Green Tea May Decrease Fractures by Improving Bone Density and Osteoblasts and Suppressing Osteoclasts

Abstract

Green tea and bone metabolism.

Osteoporosis is a major health problem in both elderly women and men. Epidemiological evidence has shown an association between tea consumption and the prevention of age-related bone loss in elderly women and men. Ingestion of green tea and green tea bioactive compounds may be beneficial in mitigating bone loss of this population and decreasing their risk of osteoporotic fractures. This review describes the effect of green tea or its bioactive components on bone health, with an emphasis on (i) the prevalence and etiology of osteoporosis; (ii) the role of oxidative stress and antioxidants in osteoporosis; (iii) green tea composition and bioavailability; (iv) the effects of green tea and its active components on osteogenesis, osteoblastogenesis, and osteoclastogenesis from human epidemiological, animal, as well as cell culture studies; (v) possible mechanisms explaining the osteoprotective effects of green tea bioactive compounds; (vi) other bioactive components in tea that benefit bone health; and (vii) a summary and future direction of green tea and bone health research and the translational aspects. In general, tea and its bioactive components might decrease the risk of fracture by improving bone mineral density and supporting osteoblastic activities while suppressing osteoclastic activities.

Shen CL, Yeh JK, Cao JJ, Wang JS
Nutr Res Jul 2009
PMID: 19700031

Citric Acid Increases Bone Density and Strength in Chicks

Abstract

Effect of dietary citric acid on the performance and mineral metabolism of broiler.

The objective of this study was to investigate the effect of dietary citric acid (CA) on the performance and mineral metabolism of broiler chicks. A total of 1720 Ross PM3 broiler chicks (days old) were randomly assigned to four groups (430 in each) and reared for a period of 35 days. The diets of groups 1, 2, 3 and 4 were supplemented with 0%, 0.25%, 0.75% or 1.25% CA by weight respectively. Feed and faeces samples were collected weekly and analysed for acid insoluble ash, calcium (Ca), phosphorus (P) and magnesium (Mg). The pH was measured in feed and faeces. At the age of 28 days, 10 birds from each group were slaughtered; tibiae were collected from each bird for the determination of bone mineral density, total ash, Ca, P, Mg and bone-breaking strength, and blood was collected for the measurement of osteocalcin, serum CrossLaps(®), Ca, P, Mg and 1,25(OH)(2)Vit-D in serum. After finishing the trial on day 37, all chicks were slaughtered by using the approved procedure. Birds that were fed CA diets were heavier (average body weights of 2030, 2079 and 2086 g in the 0.25%, 0.75% and 1.25% CA groups, respectively, relative to the control birds (1986 g). Feed conversion efficiency (weight gain in g per kg of feed intake) was also higher in birds of the CA-fed groups (582, 595 and 587 g/kg feed intake for 0.25%, 0.75% and 1.25% CA respectively), relative to the control birds (565 g/kg feed intake). The digestibility of Ca, P and Mg increased in the CA-fed groups, especially for the diets supplemented with 0.25% and 0.75% CA. Support for finding was also indicated in the results of the analysis of the tibia. At slaughter, the birds had higher carcass weights and higher graded carcasses in the groups that were fed the CA diets. The estimated profit margin was highest for birds fed the diet containing 0.25% CA. Birds of the 0.75% CA group were found to have the second highest estimated profit margin. Addition of CA up to a level of 1.25% of the diet increased performance, feed conversion efficiency, carcass weight and carcass quality, but only in numerical terms. The addition of CA up to 0.75% significantly increased the digestibility of macro minerals, bone ash content, bone mineral density and bone strength of the broiler chicks. It may, therefore, be concluded that the addition of 0.75% CA in a standard diet is suitable for growth, carcass traits, macromineral digestibility and bone mineral density of broiler chicks.

Islam KM, Schaeublin H, Wenk C, Wanner M…
J Anim Physiol Anim Nutr (Berl) Oct 2012
PMID: 22093035

High Sodium Causes Loss of Calcium in Rats

Abstract

Calcium metabolism and bone calcium content in normal and oophorectomized rats consuming various levels of saline for 12 months.

The effect of different intakes of salt for 12 mo on bone calcium content and urinary excretion of calcium and hydroxyproline were examined in sham operated and oophorectomized (OX) rats to determine the long term effects of high sodium intake and its interaction with estrogen deficiency. Sham operated (n = 24) and OX (n = 24) rats were divided into groups of six rats in a 2 x 4 design. One group of sham and one of OX rats were given 0, 2, 6 or 18 g/L sodium chloride to drink. Urine samples were collected at 0, 2, 4, 6, 10 and 12 mo for the measurement of sodium, calcium, creatinine and hydroxyproline. At the end of 12 mo, blood was taken for measurement of calcium, albumin, alkaline phosphatase and creatinine and the left femur was removed and analyzed for calcium and phosphate. Body weights of the OX rats were higher than the sham operated controls. At the start of the experiment (10 d after OX) urinary excretions of calcium and hydroxyproline were significantly higher in OX rats. However, after 4-6 mo, they were significantly lower in OX rats. Calcium excretion and hydroxyproline excretion were increased by high salt intake, and there was a significant correlation between sodium and calcium excretion (r = 0.962). Bone calcium content of OX rats was lower than their corresponding sham-operated controls. Sodium intake also had a significant effect on bone calcium content. Multiple regression analysis showed that OX and sodium intake explained 7.6% and 1.5% of the variation in bone calcium content. We conclude that high sodium intake causes increased loss of calcium and reduces bone calcium content in sham-operated as well as OX rats.

Chan EL, Swaminathan R
J. Nutr. Mar 1998
PMID: 9482774 | Free Full Text

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