Tag Archives: abstract

Calcium More or Less Than 800mg Increases Heart Risk, More or Less Than 900mg Increases All-Cause Mortality

Abstract

Dietary calcium intake and mortality risk from cardiovascular disease and all causes: a meta-analysis of prospective cohort studies.

Considerable controversy exists regarding the association between dietary calcium intake and risk of mortality from cardiovascular disease and all causes. Therefore, we performed a meta-analysis of prospective cohort studies to examine the controversy.
We identified relevant studies by searching MEDLINE, Embase, and the Cochrane Library databases between 1 September 2013 and 30 December 2013. Reference lists of relevant articles were also reviewed. Observational prospective studies that reported relative risks and 95% confidence intervals for the association of calcium intake with cardiovascular and all-cause mortality were eligible. Study-specific relative risks were pooled using a random-effects model.
In this meta-analysis, 11 prospective studies with 12 independent cohorts, involving 757,304 participants, were eligible. There was evidence of a non-linear association between dietary calcium intake and risk of mortality from cardiovascular disease (P for non-linearity <0.01) and all causes (P for non-linearity <0.01). A dose-response analysis showed a U-shaped relationship between dietary calcium intake and cardiovascular mortality. Intakes that were lower and higher than around 800 mg/day were gradually associated with a higher risk of cardiovascular mortality. For all-cause mortality, we also observed a threshold effect at intakes around 900 mg/day. The risk of all-cause mortality did not decrease further at intakes above 900 mg/day.
This meta-analysis of prospective cohort studies suggests that dietary calcium intake is associated with cardiovascular mortality in a U-shaped manner and that high dietary calcium intake (>900 mg/day) is not associated with a decreased risk of all-cause mortality.

Wang X, Chen H, Ouyang Y, Liu J…
BMC Med 2014
PMID: 25252963 | Free Full Text

From the full text:

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Calcium Supplements Associated with Increased Fracture Risk In Women

Abstract

Calcium intake and fracture risk: results from the study of osteoporotic fractures.

The relation between dietary calcium, calcium, and vitamin D supplements and the risk of fractures of the hip (n = 332), ankle (n = 210), proximal humerus (n = 241), wrist (n = 467), and vertebrae (n = 389) was investigated in a cohort study involving 9,704 US white women aged 65 years or older. Baseline assessments took place in 1986-1988 in four US metropolitan areas. Dietary calcium intake was assessed at baseline with a validated food frequency questionnaire. Data on new nonvertebral fractures were collected every 4 months during a mean of 6.6 years of follow-up; identification of new vertebral fractures was based on comparison of baseline and follow-up radiographs of the spine done a mean of 3.7 years apart. Results were adjusted for numerous potential confounders, including weight, physical activity, estrogen use, protein intake, and history of falls, osteoporosis, and fractures. There were no important associations between dietary calcium intake and the risk of any of the fractures studied. Current use of calcium supplements was associated with increased risk of hip (relative risk = 1.5, 95% confidence interval 1.1-2.0) and vertebral (relative risk = 1.4, 95% confidence interval 1.1-1.9) fractures; current use of Tums antacid tablets was associated with increased risk of fractures of the proximal humerus (relative risk = 1.7, 95% confidence interval 1.3-2.4). There was no evidence of a protective effect of vitamin D supplements. Although a true adverse effect of calcium supplements on fracture risk cannot be ruled out, it is more likely that our findings are due to inadequately controlled confounding by indications for use of supplements. In conclusion, this study did not find a substantial beneficial effect of calcium on fracture risk.

Cumming RG, Cummings SR, Nevitt MC, Scott J…
Am. J. Epidemiol. May 1997
PMID: 9149664 | Free Full Text

Calcium Intake of 903mg to 1025mg Associated with Lowest Fracture Risk, More and Less Increases Risk

Abstract

Dietary calcium intake and risk of fracture and osteoporosis: prospective longitudinal cohort study.

To investigate associations between long term dietary intake of calcium and risk of fracture of any type, hip fractures, and osteoporosis.
A longitudinal and prospective cohort study, based on the Swedish Mammography Cohort, including a subcohort, the Swedish Mammography Cohort Clinical.
A population based cohort in Sweden established in 1987.
61,433 women (born between 1914 and 1948) were followed up for 19 years. 5022 of these women participated in the subcohort.
Primary outcome measures were incident fractures of any type and hip fractures, which were identified from registry data. Secondary outcome was osteoporosis diagnosed by dual energy x ray absorptiometry in the subcohort. Diet was assessed by repeated food frequency questionnaires.
During follow-up, 14,738 women (24%) experienced a first fracture of any type and among them 3871 (6%) a first hip fracture. Of the 5022 women in the subcohort, 1012 (20%) were measured as osteoporotic. The risk patterns with dietary calcium were non-linear. The crude rate of a first fracture of any type was 17.2/1000 person years at risk in the lowest quintile of calcium intake, and 14.0/1000 person years at risk in the third quintile, corresponding to a multivariable adjusted hazard ratio of 1.18 (95% confidence interval 1.12 to 1.25). The hazard ratio for a first hip fracture was 1.29 (1.17 to 1.43) and the odds ratio for osteoporosis was 1.47 (1.09 to 2.00). With a low vitamin D intake, the rate of fracture in the first calcium quintile was more pronounced. The highest quintile of calcium intake did not further reduce the risk of fractures of any type, or of osteoporosis, but was associated with a higher rate of hip fracture, hazard ratio 1.19 (1.06 to 1.32).
Gradual increases in dietary calcium intake above the first quintile in our female population were not associated with further reductions in fracture risk or osteoporosis.

Warensjö E, Byberg L, Melhus H, Gedeborg R…
BMJ 2011
PMID: 21610048 | Free Full Text

From the full text:

• Dietary calcium intakes below approximately 700 mg per day in women were associated with an increased risk of hip fracture, any fracture, and of osteoporosis

• The highest reported calcium intake did not further reduce the risk of fractures of any type, or of osteoporosis, but was associated with a higher rate of hip fracture

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Calcium Alone Increases Hip Fractures but Lowers Total Fractures

Abstract

Effect of calcium supplementation on hip fractures.

There have been numerous studies of the effects of calcium supplementation, with or without vitamin D, on fractures. Individually, they have not provided clarity regarding calcium’s anti-fracture efficacy, though they have established that calcium does have beneficial effects on bone density throughout the skeleton in women. Meta-analysis of these data suggests that total fracture numbers are diminished. However, the data from the 5,500 women involved in trials of calcium monotherapy show consistent adverse trends in numbers of hip fractures (relative risk 1.50, 95% CI 1.06-2.12). Observational data from the Study of Osteoporotic Fractures show a similar increase in risk of hip fracture associated with calcium use. We hypothesize that reduced periosteal expansion in women using calcium supplementation might account for the differences in anti-fracture efficacy of calcium at the hip, in comparison with other sites. Until there are further trial results to clarify this area, the present findings suggest that reliance on high calcium intakes to reduce the risk of hip fracture in older women is not appropriate. In addition, those at risk should be looking to other agents with a proven capacity to prevent hip fractures, such as bisphosphonates.

Reid IR, Bolland MJ, Grey A
Osteoporos Int Aug 2008
PMID: 18286218 | Free Full Text

Furthermore, our own recent trial of calcium monotherapy suggested that there might be heterogeneity between the responses of hip and other fractures to calcium supplementation [2], with downward trends in vertebral, forearm, and total osteoporotic fractures, but a significant increase in hip fractures.

[…]

Observational studies have also assessed the relationship between calcium use and fractures. While there is a potential problem of confounding by indication, it is noteworthy that the Study of Osteoporotic Fractures reported an increase in hip fracture risk in postmenopausal women taking calcium supplements of almost identical magnitude to that found in the present meta-analysis (relative risk 1.5; 95%CI, 1.1–2.0) [18]. This consistency across the available intervention studies and a large observational study raises doubts regarding the safety of calcium monotherapy in elderly postmenopausal women, though we cannot completely preclude the possibility that these results are a chance finding arising from the smaller numbers of this particular fracture type.

The adverse effect of calcium monotherapy on hip fractures poses the question of how this could occur when the same intervention has the opposite effect on total fracture numbers.

Resveratrol Stimulates Bone Formation or Mineralization in Obese Men

Abstract

Resveratrol Increases Bone Mineral Density and Bone Alkaline Phosphatase in Obese Men: A Randomized Placebo-Controlled Trial.

Context: Metabolic syndrome (MetS) is associated with low-grade inflammation, which may harmfully affect bone. Resveratrol (RSV) possesses anti-inflammatory properties, and rodent studies suggest bone protective effects. Objective: This study sought to evaluate effects of RSV treatment on bone in men with MetS. Setting and Design: The study was conducted at Aarhus University Hospital as a randomized, double-blinded, placebo-controlled trial assessing changes in bone turnover markers, bone mineral density (BMD), and geometry. Participants: The study population comprised 74 middle-aged obese men with MetS recruited from the general community, of which 66 completed all visits. Mean age of participants was 49.3 ± 6.3 years and mean body mass index was 33.7 ± 3.6 kg/m(2). Intervention: Oral treatment with 1.000 mg RSV (RSVhigh), 150mg RSV (RSVlow), or placebo daily for 16 weeks. Main Outcome Measure: Prespecified primary endpoint was change in bone alkaline phosphatase (BAP). Results: BAP increased dose dependently with RSV (R = 0.471, P < .001), resulting in a significantly greater increase in BAP in the RSVhigh group compared with placebo at all time-points (week 4, 16.4 ± 4.2%, P < .001; week 8, 16.5 ± 4.1%, P < .001; week 16, 15.2 ± 3.7%, P < .001). Lumbar spine trabecular volumetric bone mineral density (LS vBMDtrab) also increased dose dependently with RSV (R = 0.268, P = .036), with a significant increase of 2.6 ± 1.3% in the RSVhigh group compared with placebo (P = .043). In addition, changes in BAP and LS vBMDtrab were positively correlated (R = 0.281, P = .027). No consistent changes were detected in bone density at the hip. Conclusions: Our data suggest that high-dose RSV supplementation positively affects bone, primarily by stimulating formation or mineralization. Future studies of longer duration comprising populations at risk of osteoporosis are needed to confirm these results.

Ornstrup MJ, Harsløf T, Kjær TN, Langdahl BL…
J. Clin. Endocrinol. Metab. Oct 2014
PMID: 25322274

Review: Resveratrol, Inositol, Vitamin D and K for Bone and Cardiovascular Risk

Abstract

Resveratrol, inositol, vitamin D and K in the prevention of cardiovascular and osteoporotic risk: a novel approach in peri- and postmenopause.

The prevention of cardiovascular and osteoporotic risk is a topic of great importance in the peri- and postmenopausal periods. This paper reviews the role of resveratrol, inositol, vitamin D and K in the prevention of cardiovascular and osteoporotic risk in peri- and post-. The phytoestrogen-like activity of resveratrol has potential clinical implications in the gynecological practice. In particular transresveratrol inhibits low-density lipoprotein oxidation, which is a recognized risk factor for cardiovascular diseases. Resveratrol has also a documented antiplatelet effect and may prevent cardiovascular diseases inhibiting the cardiac fibroblasts proliferation. With regard to bone health, in in vitro studies resveratrol has shown activities in osteoblastic MC3T3-E1 cells. Resveratrol also interacts with vitamin D in promoting bone health. Resveratrol is considered a caloric restriction mimetic and potentially effects factors involved in the metabolic syndrome. Myo-inositol has documented in clinical studies its effectiveness in improving the metabolic syndrome in post menopausal women. Thus the supplementation with inositol and resveratrol may be useful in the prevention of insulin resistance and consequently metabolic syndrome and cardiovascular diseases risk. Finally vitamin K2 effects calcium metabolisms and subjects with higher levels of calcium in the bones tend to have a lower frequency of vascular calcifications and a lower cardiovascular risk. Vitamin K2 also has a key role in the bone homeostasis. A supplement including resveratrol, inositol, vitamin K and vitamin D offers a novel opportunity to the woman in peri- and postmenopause.

Parazzini F
Minerva Ginecol Oct 2014
PMID: 25245999

Resveratrol May Increase Bone Length in Pre-pubertal Rabbits

Abstract

Resveratrol treatment delays growth plate fusion and improves bone growth in female rabbits.

Trans-resveratrol (RES), naturally produced by many plants, has a structure similar to synthetic estrogen diethylstilbestrol, but any effect on bone growth has not yet been clarified. Pre-pubertal ovary-intact New Zealand white rabbits received daily oral administration of either vehicle (control) or RES (200 mg/kg) until growth plate fusion occurred. Bone growth and growth plate size were longitudinally monitored by X-ray imaging, while at the endpoint, bone length was assessed by a digital caliper. In addition, pubertal ovariectomized (OVX) rabbits were treated with vehicle, RES or estradiol cypionate (positive control) for 7 or 10 weeks and fetal rat metatarsal bones were cultured in vitro with RES (0.03 µM-50 µM) and followed for up to 19 days. In ovary-intact rabbits, sixteen-week treatment with RES increased tibiae and vertebrae bone growth and subsequently improved final length. In OVX rabbits, RES delayed fusion of the distal tibia, distal femur and proximal tibia epiphyses and femur length and vertebral bone growth increased when compared with controls. Histomorphometrical analysis showed that RES-treated OVX rabbits had a wider distal femur growth plate, enlarged resting zone, increased number/size of hypertrophic chondrocytes, increased height of the hypertrophic zone, and suppressed chondrocyte expression of VEGF and laminin. In cultured fetal rat metatarsal bones, RES stimulated growth at 0.3 µM while at higher concentrations (10 μM and 50 μM) growth was inhibited. We conclude that RES has the potential to improve longitudinal bone growth. The effect was associated with a delay of growth plate fusion resulting in increased final length. These effects were accompanied by a profound suppression of VEGF and laminin expression suggesting that impairment of growth plate vascularization might be an underlying mechanism.

Karimian E, Tamm C, Chagin AS, Samuelsson K…
PLoS ONE 2013
PMID: 23840780 | Free Full Text

Resveratrol May Have Detrimental Bone Effects in Rats

Abstract

Resveratrol supplementation influences bone properties in the tibia of hindlimb-suspended mature Fisher 344 × Brown Norway male rats.

The deleterious bone effects of mechanical unloading have been suggested to be due to oxidative stress and (or) inflammation. Resveratrol has both antioxidant and anti-inflammatory properties; therefore, the study’s objective was to determine whether providing resveratrol in the low supplementation range for a short duration prevents bone loss during mechanical unloading. Mature (6 months old) Fischer 344 × Brown Norway male rats were hindlimb-suspended (HLS) or kept ambulatory for 14 days. Rats were provided either trans-resveratrol (RES; 12.5 mg/kg body mass per day) or deionized distilled water by oral gavage for 21 days (7 days prior to and during the 14 days of HLS). Bone mass was measured by dual energy X-ray absorptiometry. Bone microstructure was determined by microcomputed tomography. HLS of rats resulted in femur trabecular bone deterioration. Resveratrol supplementation did not attenuate trabecular bone deterioration in HLS rats. Unexpectedly, HLS-RES rats had the lowest tibial bone mineral content (P < 0.05), calcium content and lower cortical thickness (P < 0.05), and increased porosity compared with HLS/control rats. Plasma osteocalcin was also lower (P < 0.04) in HLS/resveratrol rats. There were no significant effects on plasma C-reactive protein, a marker of systemic inflammation, or total antioxidant capacity. However, HLS-RES rats showed a negative relationship (r(2) = 0.69, P = 0.02) between plasma osteocalcin and thiobarbituric acid reactive substances, a marker of lipid peroxidation. Based on the results, resveratrol supplementation of 6-month-old HLS male rats had no bone protective effects and possibly even detrimental bone effects.

Durbin SM, Jackson JR, Ryan MJ, Gigliotti JC…
Appl Physiol Nutr Metab Dec 2012
PMID: 23050779

Review: Resveratrol Pre-Clinical Evidence

Abstract

Resveratrol Supplementation Affects Bone Acquisition and Osteoporosis: Pre-Clinical Evidence Towards Translational Diet Therapy.

Osteoporosis is a major public health issue that is expected to rise as the global population ages. Resveratrol (RES) is a plant polyphenol with various anti-aging properties. RES treatment of bone cells results in protective effects, but dose translation from in vitro studies to clinically relevant doses is limited since bioavailability is not taken into account. The aims of this review is to evaluate in vivo evidence for a role of RES supplementation in promoting bone health to reduced osteoporosis risk and potential mechanisms of action. Due to multiple actions on both osteoblasts and osteoclasts, RES has potential to attenuate bone loss resulting from different etiologies and pathologies. Several animal models have investigated the bone protective effects of RES supplementation. Ovariectomized rodent models of rapid bone loss due to estrogen-deficiency reported that RES supplementation improved bone mass and trabecular bone without stimulating other estrogen-sensitive tissues. RES supplementation prior to age-related bone loss was beneficial. The hindlimb unloaded rat model used to investigate bone loss due to mechanical unloading showed RES supplementation attenuated bone loss in old rats, but had inconsistent bone effects in mature rats. In growing rodents, RES increased longitudinal bone growth, but had no other effects on bone. In the absence of human clinical trials, evidence for a role of RES on bone heath relies on evidence generated by animal studies. A better understanding of efficacy, safety, and molecular mechanisms of RES on bone will contribute to the determination of dietary recommendations and therapies to reduce osteoporosis. This article is part of a Special Issue entitled: Resveratol: Challenges in translating pre-clincial findigns to iproved patient outcomes.

Tou JC
Biochim. Biophys. Acta Oct 2014
PMID: 25315301

Review: Orthosilicic Acid

Abstract

Biological and therapeutic effects of ortho-silicic acid and some ortho-silicic acid-releasing compounds: New perspectives for therapy.

Silicon (Si) is the most abundant element present in the Earth’s crust besides oxygen. However, the exact biological roles of silicon remain unknown. Moreover, the ortho-silicic acid (H4SiO4), as a major form of bioavailable silicon for both humans and animals, has not been given adequate attention so far. Silicon has already been associated with bone mineralization, collagen synthesis, skin, hair and nails health atherosclerosis, Alzheimer disease, immune system enhancement, and with some other disorders or pharmacological effects. Beside the ortho-silicic acid and its stabilized formulations such as choline chloride-stabilized ortho-silicic acid and sodium or potassium silicates (e.g. M2SiO3; M= Na,K), the most important sources that release ortho-silicic acid as a bioavailable form of silicon are: colloidal silicic acid (hydrated silica gel), silica gel (amorphous silicon dioxide), and zeolites. Although all these compounds are characterized by substantial water insolubility, they release small, but significant, equilibrium concentration of ortho-silicic acid (H4SiO4) in contact with water and physiological fluids. Even though certain pharmacological effects of these compounds might be attributed to specific structural characteristics that result in profound adsorption and absorption properties, they all exhibit similar pharmacological profiles readily comparable to ortho-silicic acid effects. The most unusual ortho-silicic acid-releasing agents are certain types of zeolites, a class of aluminosilicates with well described ion(cation)-exchange properties. Numerous biological activities of some types of zeolites documented so far might probably be attributable to the ortho-silicic acid-releasing property. In this review, we therefore discuss biological and potential therapeutic effects of ortho-silicic acid and ortho-silicic acid -releasing silicon compounds as its major natural sources.

Jurkić LM, Cepanec I, Pavelić SK, Pavelić K
Nutr Metab (Lond) 2013
PMID: 23298332 | Free Full Text

The full text article (link above) has a subsection on osteoporosis:

…Interestingly, the administration of silicon in a controlled clinical study induced a significant increase in femoral bone mineral density in osteoporotic women [31]. Direct relationship between silicon content and bone formation has been shown by Moukarzel et al. [64]. They found a correlation between decreased silicon concentrations in total parenterally fed infants with a decreased bone mineral content. This was the first observation of a possible dietary deficiency of silicon in humans. A randomized controlled animal study on aged ovariectomized rats revealed that long-term preventive treatment with ch-OSA prevented partial femoral bone loss and had a positive effect on the bone turnover [65]. Dietary silicon is associated with postmenopausal bone turnover and bone mineral density at the women’s age when the risk of osteoporosis increases. Moreover, in a cohort study on 3198 middle-aged woman (50–62 years) it was shown that silicon interacts with the oestrogen status on bone mineral density, suggesting that oestrogen status is important for the silicon metabolism in bone health [66].