Tag Archives: review

Review: Moderate Alcohol May Benefit Bone, but Abuse has Toxic Effect

Abstract

Bone and the ‘comforts of life’.

Coffee drinking, smoking and especially alcohol abuse are considered to be risk factors for fractures and osteoporosis. Caffeine causes acute increase in urinary calcium excretion, but epidemiological evidence for the effects of coffee consumption on the risk of fractures is contradictory. Many, (but not all) studies point to decreased bone mass or increased fracture risk in smokers. Alcohol abuse is associated with deleterious changes in bone structure detected by histomorphometry, and with a decrease in bone mineral density (BMD).

 These changes may also be produced by factors commonly associated with alcohol abuse, e.g. nutritional deficiencies, liver damage and hypogonadism. Alcohol, however, has clear-cut direct effects on bone and mineral metabolism. Acute alcohol intoxication causes transitory hypoparathyroidism with resultant hypocalcaemia and hypercalciuria. As assessed by serum osteocalcin levels, prolonged moderate drinking decreases the function of osteoblasts, the bone-forming cells. In addition, chronic alcoholics are characterized by low serum levels of vitamin D metabolites. Thus, alcohol seems to have a direct toxic effect on bone and mineral metabolism. In contrast, it has recently been reported that moderate alcohol consumption by postmenopausal women may have a beneficial effect on bone.

Laitinen K, Välimäki M
Ann. Med. Aug 1993
PMID: 8217108

Review: Melatonin Induces Osteoblastogenesis and Inhibits Osteoclastogenesis

Abstract

Melatonin effects on bone: potential use for the prevention and treatment for osteopenia, osteoporosis, and periodontal disease and for use in bone-grafting procedures.

An important role for melatonin in bone formation and restructuring has emerged, and studies demonstrate the multiple mechanisms for these beneficial actions. Statistical analysis shows that even with existing osteoporotic therapies, bone-related disease, and mortality are on the rise, creating a huge financial burden for societies worldwide. These findings suggest that novel alternatives need to be developed to either prevent or reverse bone loss to combat osteoporosis-related fractures. The focus of this review describes melatonin’s role in bone physiology and discusses how disruption of melatonin rhythms by light exposure at night, shift work, and disease can adversely impact on bone. The signal transduction mechanisms underlying osteoblast and osteoclast differentiation and coupling with one another are discussed with a focus on how melatonin, through the regulation of RANKL and osteoprotegerin synthesis and release from osteoblasts, can induce osteoblastogenesis while inhibiting osteoclastogenesis. Also, melatonin’s free-radical scavenging and antioxidant properties of this indoleamine are discussed as yet an additional mechanism by which melatonin can maintain one’s bone health, especially oral health. The clinical use for melatonin in bone-grafting procedures, in reversing bone loss due to osteopenia and osteoporosis, and in managing periodontal disease is discussed.

Maria S, Witt-Enderby PA
J. Pineal Res. Dec 2013
PMID: 24372640

Review: Flaxseed Oil, but not Flax Lignans, may Help Bones

Abstract

Implications of dietary α-linolenic acid in bone health.

Recent evidence implies the benefit of ω-3 polyunsaturated fatty acids in bone health. Although eicosapentaenoic acid and docosahexaenoic acid, present in fish oil, have been extensively researched, much less is known about the influence of α-linolenic acid (ALA; present in flaxseeds), a metabolic precursor of eicosapentaenoic acid and docosahexaenoic acid, on bone. Our objective was to evaluate the published literature and distinguish between the individual effects of flaxseed oil and flax lignans on bone to elucidate the exact role of ALA in skeletal biology. The search was conducted in several databases resulting in 129 articles of which 30 were eligible for inclusion in this review. The studies showed that consumption of whole flaxseeds did not lead to a marked improvement of osteoporotic bones in humans and animals. However, when combined with estrogen therapy, flaxseed supplementation offered an extra benefit to bone in animal models. Similar results were found in studies conducted with flaxseed oil (predominantly ALA), but the favorable role of flaxseed oil was more obvious in various pathologic conditions (kidney disease, obesity with insulin resistance), resulting in improved bone properties. In contrast, despite a marginal estrogenic effect, the consumption of flax lignans resulted in little benefit to bone and the effect was limited to early life of females only in animal models. Based on the available studies, it could be concluded that supplementation with flaxseeds may contribute to some improvement in osteoporotic bone properties but the bone-protective effect may be attributed to ALA, not to the lignan fraction of flaxseeds.

Kim Y, Ilich JZ
Nutrition
PMID: 21726979

Review: Essential Fatty Acids may Help Bones

Abstract

Can manipulation of the ratios of essential fatty acids slow the rapid rate of postmenopausal bone loss?

The rapid rate of postmenopausal bone loss is mediated by the inflammatory cytokines interleukin-1, interleukin-6, and tumor necrosis factor alpha. Dietary supplementation with fish oil, flaxseeds, and flaxseed oil in animals and healthy humans significantly reduces cytokine production while concomitantly increasing calcium absorption, bone calcium, and bone density. Possibilities may exist for the therapeutic use of the omega-3 fatty acids, as supplements or in the diet, to blunt the increase of the inflammatory bone resorbing cytokines produced in the early postmenopausal years, in order to slow the rapid rate of postmenopausal bone loss. Evidence also points to the possible benefit of gamma-linolenic acid in preserving bone density.

Kettler DB
Altern Med Rev Feb 2001
PMID: 11207457 | Free Full Text

Review: Studies on GLA, Omega 3, and Other Fatty Acids

Abstract

Polyunsaturated fatty acids: biochemical, nutritional and epigenetic properties.

Dietary polyunsaturated fatty acids (PUFA) have effects on diverse physiological processes impacting normal health and chronic diseases, such as the regulation of plasma lipid levels, cardiovascular and immune function, insulin action and neuronal development and visual function. Ingestion of PUFA will lead to their distribution to virtually every cell in the body with effects on membrane composition and function, eicosanoid synthesis, cellular signaling and regulation of gene expression. Cell specific lipid metabolism, as well as the expression of fatty acid-regulated transcription factors, likely play an important role in determining how cells respond to changes in PUFA composition. This review will focus on recent advances on the essentiality of these molecules and on their interplay in cell physiology, leading to new perspective in different therapeutic fields.

Benatti P, Peluso G, Nicolai R, Calvani M
J Am Coll Nutr Aug 2004
PMID: 15310732 | Free Full Text

This article reviewed, among many others, the study from EPA + GLA Increases Bone Density in Elderly Women:

In a single-blind, randomized study, Kruger et al. [174] tested the interactions between calcium and DGLA + EPA in osteoporotic or osteopenic women. All of the women were living in the same institution for the elderly and fed the same low-calcium, non-vitamin D enriched foods, and had similar amounts of sunlight. Subjects were randomly assigned to DGLA + EPA or coconut oil (placebo group); in addition, all received 600 mg/day of calcium. Markers of bone formation/degradation and bone mineral density (BMD) were measured at baseline, 6, 12 and 18 months. At 18 months, osteocalcin and deoxypyridinoline levels fell significantly in both groups, indicating a decrease in bone turnover, whereas bone specific ALP rose indicating beneficial effects of calcium given to all the patients. Lumbar and femoral BMD, in contrast, showed different results in the two groups. Over the first 18 months, lumbar spine density remained the same in the treatment group, but decreased 3.2% in the placebo group. Femoral bone density increased 1.3% in the treatment group, but decreased 2.1% in the placebo group. During the second period of 18 months with all patients now on active treatment, lumbar spine density increased 3.1% in patients who remained on active treatment, and 2.3% in patients who switched from placebo to active treatment; femoral BMD in the latter group showed an increase of 4.7%.

 

Review: Vitamin K1 Cost Effectiveness for Osteoporosis

Abstract

Vitamin K to prevent fractures in older women: systematic review and economic evaluation.

To determine the clinical and cost-effectiveness of vitamin K in preventing osteoporotic fractures in postmenopausal women.
Searches were conducted in May 2007 in MEDLINE, MEDLINE In-Process, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, BIOSIS, CINAHL, DARE, NHS EED and HTA databases, AMED, NRR, Science Citation Index and Current Controlled Trials. The MEDLINE search was updated in March 2009.
Selected studies were assessed and subjected to data extraction and quality assessment using standard methods. Where appropriate, meta-analysis was carried out. A mathematical model was constructed to estimate the cost-effectiveness of vitamin K1.
The electronic literature searches identified 1078 potentially relevant articles. Of these, 14 articles relating to five trials that compared vitamin K with a relevant comparator in postmenopausal women with osteoporosis or osteopenia met the review inclusion criteria. The double-blind ECKO trial compared 5 mg of phylloquinone (vitamin K1) with placebo in Canadian women with osteopenia but without osteoporosis. Four open-label trials used 45 mg of menatetrenone (vitamin K2) in Japanese women with osteoporosis; the comparators were no treatment, etidronate or calcium. The methodological quality of the ECKO trial was good; however, all four menatetrenone trials were poorly reported and three were very small (n < 100 in each group). Phylloquinone was associated with a statistically significant reduction in the risk of clinical fractures relative to placebo [relative risk 0.46, 95% confidence interval (CI) 0.22 to 0.99]; morphometric vertebral fractures were not reported. The smaller menatetrenone trials found that menatetrenone was associated with a reduced risk of morphometric vertebral fractures relative to no treatment or calcium; however, the larger Osteoporosis Fracture (OF) study found no evidence of a reduction in vertebral fracture risk. The three smaller trials found no significant difference between treatment groups in non-vertebral fracture incidence. In the ECKO trial, phylloquinone was not associated with an increase in adverse events. In the menatetrenone trials, adverse event reporting was generally poor; however, in the OF study, menatetrenone was associated with a significantly higher incidence of skin and skin appendage lesions. No published economic evaluations of vitamin K were found and a mathematical model was thus constructed to estimate the cost-effectiveness of vitamin K1. Comparators were alendronate, risedronate and strontium ranelate. Vitamin K1 and alendronate were markedly more cost-effective than either risedronate or strontium ranelate. The base-case results favoured vitamin K1, but this relied on many assumptions, particularly on the efficacy of preventing hip and vertebral fractures. Calculation of the expected value of sampled information was conducted assuming a randomised controlled trial of 5 years’ duration comparing alendronate with vitamin K1. The costs incurred in obtaining updated efficacy data from a trial with 2000 women per arm were estimated to be a cost-effective use of resources.
There is currently large uncertainty over whether vitamin K1 is more cost-effective than alendronate; further research is required. It is unlikely that the present prescribing policy (i.e. alendronate as first-line treatment) would be altered.

Stevenson M, Lloyd-Jones M, Papaioannou D
Health Technol Assess Sep 2009
PMID: 19818211 | Free Full Text

This is a huge 158 page report. The reason they used K1 instead of K2 was:Vitamin K to prevent fractures in older women: systematic review and economic evaluation

No formal evaluation of vitamin K2 has been undertaken for a number of reasons. This intervention is currently not permitted as a food supplement in the EU because there is no evidence for its independent role in health26 and the price of the intervention is unknown. Additionally, the fracture efficacy data have wide confidence intervals, all of which spanned unity, and the only large (n > 1500 patients per arm) RCT reported a RR of 1.01 for vitamin K2 compared with calcium or no active intervention.

 

 

Review: Nutrition for Osteoporosis

Abstract

Osteoporosis prevention and nutrition.

Although calcium and vitamin D have been the primary focus of nutritional prevention of osteoporosis, recent research has clarified the importance of several additional nutrients and food constituents. Further, results of calcium and vitamin D supplementation trials have been inconsistent, suggesting that reliance on this intervention may be inadequate. In addition to dairy, fruit and vegetable intake has emerged as an important modifiable protective factor for bone health. Several nutrients, including magnesium, potassium, vitamin C, vitamin K, several B vitamins, and carotenoids, have been shown to be more important than previously realized. Rather than having a negative effect on bone, protein intake appears to benefit bone status, particularly in older adults. Regular intake of cola beverages shows negative effects and moderate alcohol intake shows positive effects on bone, particularly in older women. Current research on diet and bone status supports encouragement of balanced diets with plenty of fruit and vegetables, adequate dairy and other protein foods, and limitation of foods with low nutrient density.

Tucker KL
Curr Osteoporos Rep Dec 2009
PMID: 19968914

Review: Vitamin K and Bone Health 1998-2008

Abstract

Update on the role of vitamin K in skeletal health.

A protective role for vitamin K in bone health has been suggested based on its role as an enzymatic cofactor. In observational studies, vitamin K insufficiency is generally associated with lower bone mass and increased hip fracture risk. However, these findings are not supported in randomized controlled trials (RCT) of phylloquinone (vitamin K(1)) supplementation and bone loss at the hip in the elderly. This suggests that increased vegetable and legume intakes may simultaneously improve measures of vitamin K status and skeletal health, even though the mechanisms underlying these improvements may be independent of each other. Menaquinone-4 (vitamin K(2)), when given at pharmacological doses, appears to protect against fracture risk and bone loss at the spine. However, there are emerging data that suggest the efficacy of vitamin K supplementation on bone loss is inconclusive.

Shea MK, Booth SL
Nutr. Rev. Oct 2008
PMID: 18826451 | Free Full Text

This is a great review of the different forms of Vitamin K and their benefits for bone. The full study includes a table listing many studies dated from 1998 to 2008 with their outcomes. I highly recommend reading the full text.

MK-4 in doses of 45 mg/d is used as a pharmacological treatment for osteoporosis in Japan, so there are numerous randomized control studies that have assessed the efficacy of MK-4 supplementation on skeletal health. Such doses cannot be attained from the diet, regardless of the form of vitamin K consumed. Phylloquinone from the diet is converted to MK-4 in certain tissues, including bone, but the proportion of phylloquinone that is converted is not known and no dose-dependent data are available for this conversion.

[…]

As reviewed in an earlier volume of this journal,60 studies indicate a therapeutic dose (45 mg/day) of MK-4 has a beneficial effect on spine or metacarpal BMD and fracture61–76 (Table 2). There is also improvement in bone turnover, as measured by circulating markers of bone formation and bone resorption, in response to MK-4 supplementation studies.71,72,76,77 In a separate systematic review and analysis of randomized clinical trials assessing the influence of vitamin K supplementation on hip fracture, Cockayne et al.78 concluded that supplementation with MK-4 for longer than 6 months reduces risk for hip and vertebral fracture. Included in that analysis were 12 studies that used daily doses of 45 mg/d of MK-4. As discussed by the authors, several of the studies used for the meta-analysis lacked sufficient sample size,64–66,70,73,79 were non-placebo-controlled intervention trials,70–74,76,77,80 and/or used concurrent treatment with calcium and/or vitamin D.62,69,75,76

It was subsequently disclosed that a large unpublished surveillance study conducted in Japan (n > 3000) did not find a protective effect of MK-4 supplementation (45 mg/day) on bone loss and fracture in the elderly, and that inclusion of this study may have altered the results of the meta-analysis.81 More recently, two placebo-controlled studies with large sample sizes reported no protective effect of 45 mg/d of MK-4 on hip BMD.59,67 Prior to these two publications, the majority of MK-4 supplementation studies did not report hip BMD as an outcome (Table 2). Given the heterogeneous quality of the studies used and considering the null findings of more recent, larger, placebo-controlled trials and unpublished surveillance data, prior systematic reviews and meta-analyses may need to be revisited.

 

Review: Vitamin K Evidence is Mixed

Abstract

Vitamin K and bone health in older adults.

Vitamin K is one of several nutrients that have been linked with bone health. In particular, there is an emerging literature regarding the questionable efficacy of vitamin K supplementation in reducing age-related bone loss. This review aims to summarize the role of vitamin K in bone health in older adults and discuss the clinical implications from a select few human studies. The evidence for vitamin K supplementation in older adults is mixed. Although the observational studies have shown linkages between vitamin K intake and lower risk of fractures in this population, the current evidence from randomized controlled trials is not strongly supportive of vitamin K supplementation in older adults for the intent of improving bone health.

Shah K, Gleason L, Villareal DT
J Nutr Gerontol Geriatr 2014
PMID: 24597993

Review: Vitamin K May Reduce Fractures

Abstract

Vitamin K and bone health.

Vitamin K has been purported to play an important role in bone health. It is required for the gamma-carboxylation of osteocalcin (the most abundant noncollagenous protein in bone), making osteocalcin functional. There are 2 main forms (vitamin K1 and vitamin K2), and they come from different sources and have different biological activities. Epidemiologic studies suggest a diet high in vitamin K is associated with a lower risk of hip fractures in aging men and women. However, randomized controlled trials of vitamin K1 or K2 supplementation in white populations did not increase bone mineral density at major skeletal sites. Supplementation with vitamin K1 and K2 may reduce the risk of fractures, but the trials that examined fractures as an outcome have methodological limitations. Large well-designed trials are needed to compare the efficacies of vitamin K1 and K2 on fractures. We conclude that currently there is not enough evidence to recommend the routine use of vitamin K supplements for the prevention of osteoporosis and fractures in postmenopausal women.

Hamidi MS, Gajic-Veljanoski O, Cheung AM
J Clin Densitom. 2013 Oct-Dec
PMID: 24090644