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Soy Isoflavones + Vitamin D3 Improve Bone Density, Stimulate Osteoblasts, and Inhibit Osteoclasts in Ovariectomized Rats

Abstract

Combined effect of soy isoflavones and vitamin D3 on bone loss in ovariectomized rats.

Several studies have shown that soy isoflavones have estrogen-like activities and might constitute an alternative to hormone replacement treatment. The present study investigated the effects of soy isoflavones alone and combined with vitamin D3 on prevention of bone loss.
Sprague-Dawley rats were sham-operated (n = 8) or ovariectomized (OVX; n = 40), and then the OVX rats were randomly assigned to five groups that were untreated or treated for 14 wk with vitamin D3, 17β-estradiol, soy isoflavone extract (SIE), or vitamin D3 plus SIE. The effects of the isoflavones and 1α,25(OH)(2)D(3) on cultured osteoblasts and osteoclasts also were investigated.
In OVX rats, the bone mineral density and trabecular bone volume loss were improved by 17β-estradiol, SIE, or SIE plus vitamin D3 treatment. SIE treatment was more effective than vitamin D3 or 17β-estradiol in inhibiting increases in serum tumor necrosis factor-α levels and osteoblast osteoprotegerin expression. SIE plus vitamin D3 was more effective in increasing osterix expression than each alone. Bone cell cultures showed that the isoflavones induced preosteoblasts to differentiate into osteoblasts and increased osteoblast mineralization. Isoflavones inhibited preosteoclasts and osteoclast proliferation and decreased osteoclast resorption. The combination of isoflavones plus 1α,25(OH)(2)D(3) showed additive effects on the increase in cell proliferation of cultured preosteoblasts.
Treatment with soy isoflavones might be an alternative to hormone replacement therapy in decreasing bone loss from postmenopausal estrogen deficiency. In addition, there are further effects on increasing transcription factor osterix expression and preosteoblast proliferation when these were combined with vitamin D3.

Chang KL, Hu YC, Hsieh BS, Cheng HL…
Nutrition Jan 2013
PMID: 22858193

Clothing Style May Lower Vitamin D and Increase Fractures in Italian Nuns

Abstract

Low 25-hydroxyvitamin D levels and low bone density assessed by quantitative ultrasonometry in a cohort of postmenopausal Italian nuns.

This study was aimed at evaluating the effect of clothing style on bone mass and fractures in 70 postmenopausal nuns residing in a monastery in Naples. Sixty healthy women matched for age, body mass index, and menopausal status were enrolled as controls. Each participant underwent measurement by quantitative ultrasonometry (QUS) using a DBM Sonic Bone Profiler (IGEA S.p.A., Carpi, Modena, Italy) at proximal phalanges, responded to questionnaires regarding lifestyle, calcium intake, medical history, including clinical fragility fractures, and was submitted to routine biochemical assessment. A significant reduction in ultrasonometric parameters of bone mass was found in nuns compared with controls (p from 0.007 to <0.0001). 25-hydroxyvitamin D (25-OH vit D) levels were reduced by more than 50% in nuns (9.8 ± 4.2 vs 23.5 ± 5.7 nmol/L; p < 0.0001), whereas their estimated daily calcium intake was higher (1.004 ± 0.23 vs 0.721 ± 0.25 g of controls; p = 0.0007). Age at menopause was significantly lower in nuns’ group (p = 0.016). Incidence of fractures was higher in nuns (39% vs 10%; p = 0.0029), and the best predictors of fractures were age at menopause (odds ratio [OR]: 1.12; 95% confidence interval [CI]: 1.01-1.30), amplitude-dependent speed of sound T-score (OR: 1.15; 95% CI: 1.03-1.63), and bone transmission time T-score (OR: 1.30; 95% CI: 1.15-1.81). This study documented low 25-OH vit D levels, increased frequency of clinical fractures, and low bone mass detected by QUS in Southern Italian nuns.

Nuzzo V, Zuccoli A, de Terlizzi F, Colao A…
J Clin Densitom
PMID: 22832035

Low-Dose Estrogen Increases Bone Density in Postmenopausal Women

Abstract

Effects of a low-dose oral estrogen only treatment on bone mineral density and quantitative ultrasonometry in postmenopausal women.

The aim of this study was to evaluate an oral low-dose estrogen therapy on bone mineral density (BMD) and quantitative ultrasonometry (QUS) in osteopenic postmenopausal women.
This prospective, open-label cohort study investigated 120 postmenopausal hysterectomized women. Forty-seven women had been treated with 0.3 mg conjugated equine estrogen daily (ET). Primary end point was the change in BMD at the spine after 24 months. Secondary end points were among other changes in QUS at the os calcis and phalanges.
After matching 42 participants in the ET group, 42 controls were analyzed. The change in BMD differed significantly after 24 months (p = 0.019). Women on ET showed significant increase of spine and hip Z-score, whereas controls showed significant decreases in spine and total hip BMD. In QUS of the os calcis and the phalanges, a number of variables showed a significant improvements with ET.
Our results comprised a positive effect of an oral low-dose estrogen therapy on BMD. Limitations of the study are the small sample size and the open-label, non-randomized cohort study design. The findings are in accordance to the common literature and support the use of ET in the primary prevention of postmenopausal bone loss.

Ziller M, Herwig J, Ziller V, Kauka A…
Gynecol. Endocrinol. Dec 2012
PMID: 22835159

Low to Moderate Alcohol May Protect Bone

Abstract

Alcohol consumption and bone mineral density in elderly women.

Findings regarding alcohol consumption and bone mineral density (BMD) in elderly women have been inconsistent. The objective of the present study was to explore the association of alcohol intake with BMD in elderly women.
This cohort study included women from the population-based Kuopio Osteoporosis Risk Factor and Prevention – Fracture Prevention Study (OSTPRE-FPS). Alcohol intake and potential confounders were assessed at baseline and after 3 years of follow-up using a lifestyle questionnaire. In addition, an FFQ was distributed in the third year to measure dietary intake, including alcohol. Women underwent BMD measurements at the femoral neck and lumbar spine at baseline and after 3 years of follow-up.
Kuopio Province, Finland.
Three hundred elderly women (mean age 67·8 years) who provided both BMD measurements and FFQ data.
Alcohol consumption estimated from the FFQ and lifestyle questionnaire was significantly associated with BMD at both measurement sites after adjustment for potential confounders, including lifestyle and dietary factors (P < 0·05). Using the FFQ, women drinking >3 alcoholic drinks/week had significantly higher BMD than abstainers, 12·0 % at the femoral neck and 9·2 % at the lumbar spine. Results based on the lifestyle questionnaire showed higher BMD values for all alcohol-consuming women at the femoral neck and for women drinking 1-3 alcoholic beverages/week at the lumbar spine, compared with non-users.
The results from OSTPRE-FPS suggest that low to moderate alcohol intake may exert protective effects on bone health in elderly women.

Sommer I, Erkkilä AT, Järvinen R, Mursu J…
Public Health Nutr Apr 2013
PMID: 22800300

Fruit Associated With Bone Density and Content in Chinese Women

Abstract

Fruit and vegetable intake and bone mass in Chinese adolescents, young and postmenopausal women.

Previous studies showed an inconsistent association of fruit and vegetable consumption with bone health. We assessed the associations in Chinese adolescents, young and postmenopausal women.
A cross-sectional study conducted in China during July 2009 to May 2010.
Bone mineral density (BMD) and content (BMC) at the whole body, lumbar spine and left hip were measured with dual-energy X-ray absorptiometry. Dietary intakes were assessed using an FFQ. All these values were separately standardized into Z-scores in each population subgroup.
One hundred and ten boys and 112 girls (11-14 years), 371 young women (20-34 years, postpartum within 2 weeks) and 333 postmenopausal women (50-70 years).
After adjustment for potential covariates, analysis of covariance showed a significantly positive association between fruit intake and BMD and BMC in all participants combined (P-trend: < 0.001 to 0.002). BMD Z-score increased by 0.25 (or 2.1 % of the mean), 0.22 (3.5 %), 0.23 (3.0 %) and 0.25 (3.5 %), and BMC Z-score increased by 0.33 (5.7 %), 0.25 (5.8 %), 0.34 (5.9 %) and 0.29 (4.7 %), at the total body, lumbar spine, total hip and femoral neck in participants belonging to the top tertile compared with the bottom tertile of fruit intake (all P < 0.05), respectively. There was no significant association between vegetable intake and bone mass at all bone sites studied except for total body BMD (P = 0.030). Relatively more pronounced effects were observed in boys and postmenopausal women.
Our findings add to the existing evidence that fruits and vegetables may have a bone sparing effect.

Li JJ, Huang ZW, Wang RQ, Ma XM…
Public Health Nutr Jan 2013
PMID: 22717072

Blueberry May Prevent Collagen and Bone Loss in Rat Cells

Abstract

Blueberry consumption prevents loss of collagen in bone matrix and inhibits senescence pathways in osteoblastic cells.

Ovariectomy (OVX)-induced bone loss has been linked to increased bone turnover and higher bone matrix collagen degradation as the result of osteoclast activation. However, the role of degraded collagen matrix in the fate of resident bone-forming cells is unclear. In this report, we show that OVX-induced bone loss is associated with profound decreases in collagen 1 and Sirt1. This was accompanied by increases in expression and activity of the senescence marker collagenase and expression of p16/p21 in bone. Feeding a diet supplemented with blueberries (BB) to pre-pubertal rats throughout development or only prior to puberty [postnatal day 21 (PND21) to PND34] prevents OVX-induced effects on expression of these molecules at PND68. In order to provide more evidence and gain a better understanding on the association between bone collagen matrix and resident bone cell fate, in vitro studies on the cellular senescence pathway using primary calvarial cells and three cell lines (ST2 cells, OB6, and MLO-Y4) were conducted. We found that senescence was inhibited by collagen in a dose-response manner. Treatment of cells with serum from OVX rats accelerated osteoblastic cell senescence pathways, but serum from BB-fed OVX rats had no effect. In the presence of low collagen or treatment with OVX rat serum, ST2 cells exhibited higher potential to differentiate into adipocytes. Finally, we demonstrated that bone cell senescence is associated with decreased Sirt1 expression and activated p53, p16, and p21. These results suggest that (1) a significant prevention of OVX-induced bone cell senescence from adult rats can occur after only 14 days consumption of a BB-containing diet immediately prior to puberty, and (2) the molecular mechanisms underlying this effect involves, at least in part, prevention of collagen degradation.

Zhang J, Lazarenko OP, Blackburn ML, Badger TM…
Age (Dordr) Jun 2013
PMID: 22555620

Review: Incretins May Stimulate Osteoblasts and Suppress Osteoclasts

Abstract

[Incretin and bone].

Gastrointestinal hormones including gastric inhibitory polypeptide (GIP) and glucagon-like peptide (GLP) -1 are incretin, which are secreted immediately after meal ingestion and stimulate insulin secretion from pancreatic beta-cells. Characterization of extra-pancreatic GIP and GLP-1 receptors has revealed that these hormones regulate bone turnover. GIP intermittently stimulates osteoblasts and GLP-1 suppresses osteoclasts through a calcitonin-dependent pathway to increase the bone volume.

Yamada Y
Clin Calcium Sep 2009
PMID: 19721203

Vitamin K2 (MK-4) + D + Calcium Reduces Lifetime Probability of Fracture by 25%

Abstract

Vitamin K supplementation for the primary prevention of osteoporotic fractures: is it cost-effective and is future research warranted?

Lifetime supplementation with vitamin K, vitamin D(3), and calcium is likely to reduce fractures and increase survival in postmenopausal women. It would be a cost-effective intervention at commonly used thresholds, but high uncertainty around the cost-effectiveness estimates persists. Further research on the effect of vitamin K on fractures is warranted.
Vitamin K might have a role in the primary prevention of fractures, but uncertainties about its effectiveness and cost-effectiveness persist.
We developed a state-transition probabilistic microsimulation model to quantify the cost-effectiveness of various interventions to prevent fractures in 50-year-old postmenopausal women without osteoporosis. We compared no supplementation, vitamin D(3) (800 IU/day) with calcium (1,200 mg/day), and vitamin K(2) (45 mg/day) with vitamin D(3) and calcium (at the same doses). An additional analysis explored replacing vitamin K(2) with vitamin K(1) (5 mg/day).
Adding vitamin K(2) to vitamin D(3) with calcium reduced the lifetime probability of at least one fracture by 25%, increased discounted survival by 0.7 quality-adjusted life-years (QALYs) (95% credible interval (CrI) 0.2; 1.3) and discounted costs by $8,956, yielding an incremental cost-effectiveness ratio (ICER) of $12,268/QALY. At a $50,000/QALY threshold, the probability of cost-effectiveness was 95% and the population expected value of perfect information (EVPI) was $28.9 billion. Adding vitamin K(1) to vitamin D and calcium reduced the lifetime probability of at least one fracture by 20%, increased discounted survival by 0.4 QALYs (95% CrI -1.9; 1.4) and discounted costs by $4,014, yielding an ICER of $9,557/QALY. At a $50,000/QALY threshold, the probability of cost-effectiveness was 80% while the EVPI was $414.9 billion. The efficacy of vitamin K was the most important parameter in sensitivity analyses.
Lifetime supplementation with vitamin K, vitamin D(3), and calcium is likely to reduce fractures and increase survival in postmenopausal women. Given high uncertainty around the cost-effectiveness estimates, further research on the efficacy of vitamin K on fractures is warranted.

Gajic-Veljanoski O, Bayoumi AM, Tomlinson G, Khan K…
Osteoporos Int Nov 2012
PMID: 22398856

Melatonin Implants Influence Bone Repair in Rabbits

Abstract

Melatonin promotes angiogenesis during repair of bone defects: a radiological and histomorphometric study in rabbit tibiae.

The pineal gland hormone, melatonin, is an immunomodulator and neuroendocrine hormone; it also stimulates monocyte, cytokine and fibroblast proliferations, which influence angiogenesis. The aim of this study was to investigate the effects of melatonin on angiogenesis during bone defect repair by means of radiological and histomorphometric evaluations of bone response to melatonin implants.
Twenty New Zealand rabbits weighing 3,900-4,500 g were used. Twenty melatonin implants were inserted in the proximal metaphyseal area of the animals’ right tibia and 20 control areas were located in the left proximal metaphyseal area. Following implantation, the animals were sacrificed in groups of five, after 1, 2, 3 and 4 weeks, respectively. Anteroposterior and lateral radiographs were taken, and radiographic thermal imaging analysis was performed for all groups at different time stages following implant insertion. Samples were sectioned at 5 μm and stained using Hematoxylin-Eosin and Masson’s trichrome, supplementing radiographic findings with histomorphometric analysis.
After 4 weeks, radiological images showed complete repair of the bone defects. No healed or residual bone alterations attributable to the presence of the melatonin implant were observed. Histomorphometric analysis at 4 weeks showed the presence of a higher density newly formed bone. There were statistically significant differences in the length of cortical formation between the melatonin group and the control group during the first weeks of the study; there were also statistically significant differences in the number of vessels observed in the melatonin groups at the first two study stages.
Melatonin may have potential beneficial effects on bone defect repair.

Ramírez-Fernández MP, Calvo-Guirado JL, de-Val JE, Delgado-Ruiz RA…
Clin Oral Investig Jan 2013
PMID: 22323056

Genistein + EPA + DHA + Vitamin D + K1 Increases Bone Density in Postmenopausal Women

Abstract

Effect of a combination of genistein, polyunsaturated fatty acids and vitamins D3 and K1 on bone mineral density in postmenopausal women: a randomized, placebo-controlled, double-blind pilot study.

Many postmenopausal women desire non-pharmaceutical alternatives to hormone therapy for protection against osteoporosis. Soybean isoflavones, especially genistein, are being studied for this purpose. This study examined the effects of synthetic genistein in combination with other potential bone-protective dietary molecules on bone mineral density (BMD) in early postmenopausal women.
In this 6-month double-blind pilot study, 70 subjects were randomized to receive daily either calcium only or the geniVida™ bone blend (GBB), which consisted of genistein (30 mg/days), vitamin D3 (800 IU/days), vitamin K1 (150 μg/days) and polyunsaturated fatty acids (1 g polyunsaturated fatty acids as ethyl ester: eicosapentaenoic acid/docosahexaenoic acid ratio = ~2/1). Markers of bone resorption and formation and BMD at the femoral neck, lumbar spine, Ward’s triangle, trochanter and intertrochanter, total hip and whole body were assessed.
Subjects supplemented with the GBB (n = 30) maintained femoral neck BMD, whereas in the placebo group (n = 28), BMD significantly decreased (p = 0.007). There was also a significant difference (p < 0.05) in BMD between the groups at Ward’s triangle in favor of the GBB group. Bone-specific alkaline phosphatase and N-telopeptide significantly increased in the GBB group in comparison with those in baseline and in the placebo group. The GBB was well tolerated, and there were no significant differences in adverse events between groups.
The GBB may help to prevent osteoporosis and reduce fracture risk, at least at the hip, in postmenopausal women. Larger and longer-term clinical trials are warranted.

Lappe J, Kunz I, Bendik I, Prudence K…
Eur J Nutr Feb 2013
PMID: 22302614 | Free Full Text