Tag Archives: review

Review: Phytochemicals for Bone Osteoporosis

Abstract

Regulatory mechanism of food factors in bone metabolism and prevention of osteoporosis.

Aging induces a decrease in bone mass, and osteoporosis with its accompanying decrease in bone mass is widely recognized as a major public health problem. Bone loss with increasing age may be due to decreased bone formation and increased bone resorption. Pharmacologic and nutritional factors may prevent bone loss with aging, although chemical compounds in food and plants which act on bone metabolism are poorly understood. We have found that isoflavones (including genistein and daidzein), which are contained in soybeans, have a stimulatory effect on osteoblastic bone formation and an inhibitory effect on osteoclastic bone resorption, thereby increasing bone mass. Menaquinone-7, an analogue of vitamin K(2) which is abundant in fermented soybeans, has been demonstrated to stimulate osteoblastic bone formation and to inhibit osteoclastic bone resorption. Of various carotenoids, beta-cryptoxanthin, which is abundant in Satsuma mandarin (Citrus unchiu MARC), has a stimulatory effect on osteoblastic bone formation and an inhibitory effect on osteoclastic bone resorption. The supplementation of these factors has a preventive effect on bone loss induced by ovariectomy in rats, which are an animal model of osteoporosis, and their intake has been shown to have a stimulatory effect on bone mass in humans. Factors with an anabolic effect on bone metabolism were found in extracts obtained from wasabi leafstalk (Wasabi japonica MATSUM), the marine alga Sargassum horneri, and bee pollen Cistus ladaniferus. Phytocomponent p-hydroxycinnamic acid was also found to have an anabolic effect on bone metabolism. Food chemical factors thus play a role in bone health and may be important in the prevention of bone loss with increasing age.

Yamaguchi M
Yakugaku Zasshi Nov 2006
PMID: 17077614 | Free Full Text

Review: Exercises to Reduce Falls, and Improve Gait and Balance

Abstract

Effects of different exercise interventions on risk of falls, gait ability, and balance in physically frail older adults: a systematic review.

The aim of this review was to recommend training strategies that improve the functional capacity in physically frail older adults based on scientific literature, focusing specially in supervised exercise programs that improved muscle strength, fall risk, balance, and gait ability. Scielo, Science Citation Index, MEDLINE, Scopus, Sport Discus, and ScienceDirect databases were searched from 1990 to 2012. Studies must have mentioned the effects of exercise training on at least one of the following four parameters: Incidence of falls, gait, balance, and lower-body strength. Twenty studies that investigated the effects of multi-component exercise training (10), resistance training (6), endurance training (1), and balance training (3) were included in the present revision. Ten trials investigated the effects of exercise on the incidence of falls in elderly with physical frailty. Seven of them have found a fewer falls incidence after physical training when compared with the control group. Eleven trials investigated the effects of exercise intervention on the gait ability. Six of them showed enhancements in the gait ability. Ten trials investigated the effects of exercise intervention on the balance performance and seven of them demonstrated enhanced balance. Thirteen trials investigated the effects of exercise intervention on the muscle strength and nine of them showed increases in the muscle strength. The multi-component exercise intervention composed by strength, endurance and balance training seems to be the best strategy to improve rate of falls, gait ability, balance, and strength performance in physically frail older adults.

Cadore EL, Rodríguez-Mañas L, Sinclair A, Izquierdo M
Rejuvenation Res Apr 2013
PMID: 23327448 | Free Full Text

Review: Nutrients for Bone Health

Abstract

Essential Nutrients for Bone Health and a Review of their Availability in the Average North American Diet.

Osteoporosis and low bone mineral density affect millions of Americans. The majority of adults in North America have insufficient intake of vitamin D and calcium along with inadequate exercise. Physicians are aware that vitamin D, calcium and exercise are essential for maintenance of bone health. Physicians are less likely to be aware that dietary insufficiencies of magnesium, silicon, Vitamin K, and boron are also widely prevalent, and each of these essential nutrients is an important contributor to bone health. In addition, specific nutritional factors may improve calcium metabolism and bone formation. It is the authors’ opinion that nutritional supplements should attempt to provide ample, but not excessive, amounts of factors that are frequently insufficient in the typical American diet. In contrast to dietary insufficiencies, several nutrients that support bone health are readily available in the average American diet. These include zinc, manganese, and copper which may have adverse effects at higher levels of intake. Some multivitamins and bone support products provide additional quantities of nutrients that may be unnecessary or potentially harmful. The purpose of this paper is to identify specific nutritional components of bone health, the effects on bone, the level of availability in the average American diet, and the implications of supplementation for each nutritional component. A summary of recommended dietary supplementation is included.

Price CT, Langford JR, Liporace FA
Open Orthop J 2012
PMID: 22523525 | Free Full Text

Oral intake of 2 gm/day of strontium ranelate have improved bone strength and reduced fracture rates in women with osteoporosis, but there are reports of increased risks of venous blood clots and memory loss [82, 87].

Review: Nutrients Involved in Maintaining Healthy Bone

Abstract

Update on nutrients involved in maintaining healthy bone.

Osteoporosis is a leading cause of morbidity and mortality in the elderly and influences quality of life, as well as life expectancy. Currently, there is a growing interest among the medical scientists in search of specific nutrients and/or bioactive compounds of natural origin for the prevention of disease and maintenance of bone health. Although calcium and vitamin D have been the primary focus of nutritional prevention of osteoporosis, a recent research has clarified the importance of several additional nutrients and food constituents. Based on this review of the literature, supplementation with vitamins B, C, K, and silicon could be recommended for proper maintenance of bone health, although further clinical studies are needed. The results of studies on long-chain polyunsaturated fatty acids, potassium, magnesium, copper, selenium, and strontium are not conclusive, although studies in vitro and in animal models are interesting and promising.

Rondanelli M, Opizzi A, Perna S, Faliva MA
Endocrinol Nutr Apr 2013
PMID: 23273614

Review: Zinc Compounds in Osteoporosis

Abstract

Role of nutritional zinc in the prevention of osteoporosis.

Zinc is known as an essential nutritional factor in the growth of the human and animals. Bone growth retardation is a common finding in various conditions associated with dietary zinc deficiency. Bone zinc content has been shown to decrease in aging, skeletal unloading, and postmenopausal conditions, suggesting its role in bone disorder. Zinc has been demonstrated to have a stimulatory effect on osteoblastic bone formation and mineralization; the metal directly activates aminoacyl-tRNA synthetase, a rate-limiting enzyme at translational process of protein synthesis, in the cells, and it stimulates cellular protein synthesis. Zinc has been shown to stimulate gene expression of the transcription factors runt-related transcription factor 2 (Runx2) that is related to differentiation into osteoblastic cells. Moreover, zinc has been shown to inhibit osteoclastic bone resorption due to inhibiting osteoclast-like cell formation from bone marrow cells and stimulating apoptotic cell death of mature osteoclasts. Zinc has a suppressive effect on the receptor activator of nuclear factor (NF)-kappaB ligand (RANKL)-induced osteoclastogenesis. Zinc transporter has been shown to express in osteoblastic and osteoclastic cells. Zinc protein is involved in transcription. The intake of dietary zinc causes an increase in bone mass. beta-Alanyl-L: -histidinato zinc (AHZ) is a zinc compound, in which zinc is chelated to beta-alanyl-L: -histidine. The stimulatory effect of AHZ on bone formation is more intensive than that of zinc sulfate. Zinc acexamate has also been shown to have a potent-anabolic effect on bone. The oral administration of AHZ or zinc acexamate has the restorative effect on bone loss under various pathophysiologic conditions including aging, skeletal unloading, aluminum bone toxicity, calcium- and vitamin D-deficiency, adjuvant arthritis, estrogen deficiency, diabetes, and fracture healing. Zinc compounds may be designed as new supplementation factor in the prevention and therapy of osteoporosis.

Yamaguchi M
Mol. Cell. Biochem. May 2010
PMID: 20035439

Review: Zinc-Carnosine and Bone Resorption

Abstract

beta-Alanyl-L-histidinato zinc and bone resorption.

1. beta-Alanyl-L-histidinato zinc (AHZ), in which zinc is chelated to beta-alanyl-L-histidine, is a new zinc compound. beta-Alanyl-L-histidine can uniquely chelated zinc ion in various essential trace metals. More recently, it has been demonstrated that this compound has more intensive effect than zinc sulfate on bone metabolism, suggesting a role as pharmacological tool in osteoporosis. This review describes mainly the action of AHZ on bone resorption as summarized in the following.
2. The prolonged oral administration of AHZ (10-100 mg/kg/day) can completely prevent bone loss in the femur of ovariectomized rats, indicating the preventive effect of AHZ on bone resorption in vivo.
3. The decrease in bone calcium content induced by various bone resorbing factors was completely inhibited by the presence of AHZ (10(-6)-10(-4) M) in bone tissue culture system in vitro.
4. Many bone resorbing agents can stimulate the formation (differentiation) of osteoclasts from marrow cells. AHZ (10(-6)-10(-4) M) clearly inhibited osteoclast-like cell formation in mouse marrow culture in vitro.
5. AHZ may act on the process of parathyroid hormone-induced protein kinase C activation which is involved in Ca(2+)-signaling in osteoclastic cells.

Yamaguchi M
Gen. Pharmacol. Oct 1995
PMID: 7590105

Review: Alkaline Diets and the Acid Load Theory are Bunk – 2013

Abstract

Nutritional disturbance in acid-base balance and osteoporosis: a hypothesis that disregards the essential homeostatic role of the kidney.

The nutritional acid load hypothesis of osteoporosis is reviewed from its historical origin to most recent studies with particular attention to the essential but overlooked role of the kidney in acid-base homeostasis. This hypothesis posits that foods associated with an increased urinary acid excretion are deleterious for the skeleton, leading to osteoporosis and enhanced fragility fracture risk. Conversely, foods generating neutral or alkaline urine would favour bone growth and Ca balance, prevent bone loss and reduce osteoporotic fracture risk. This theory currently influences nutrition research, dietary recommendations and the marketing of alkaline salt products or medications meant to optimise bone health and prevent osteoporosis. It stemmed from classic investigations in patients suffering from chronic kidney diseases (CKD) conducted in the 1960s. Accordingly, in CKD, bone mineral mobilisation would serve as a buffer system to acid accumulation. This interpretation was later questioned on both theoretical and experimental grounds. Notwithstanding this questionable role of bone mineral in systemic acid-base equilibrium, not only in CKD but even more in the absence of renal impairment, it is postulated that, in healthy individuals, foods, particularly those containing animal protein, would induce ‘latent’ acidosis and result, in the long run, in osteoporosis. Thus, a questionable interpretation of data from patients with CKD and the subsequent extrapolation to healthy subjects converted a hypothesis into nutritional recommendations for the prevention of osteoporosis. In a historical perspective, the present review dissects out speculation from experimental facts and emphasises the essential role of the renal tubule in systemic acid-base and Ca homeostasis.

Bonjour JP
Br. J. Nutr. Oct 2013
PMID: 23551968 | Free Full Text

…experiments carried out among patients suffering from severe metabolic acidosis caused by renal insufficiency, or among healthy subjects made acidotic by administering NH4Cl, suggested the involvement of bone tissue in maintaining the acid–base balance. This hypothesis was later refuted on the basis of both theoretical and experimental arguments. Despite this rebuttal, the hypothesis was put forward that bone could play a buffering role, with the consideration that nutrients, particularly animal proteins with their acid load, could be a major cause of osteoporosis. Several recent human studies have shown that there is no relationship between nutritionally induced variations of urinary acid excretion and Ca balance, bone metabolism and the risk of osteoporotic fractures. Variations in human diets across a plausible range of intakes have been shown to have no effect on blood pH. Consistent with this lack of a mechanistic basis, long-term studies of alkalinising diets have shown no effect on the age-related change in bone fragility. Consequently, advocating the consumption of alkalinising foods or supplements and/or removing animal protein from the human diet is not justified by the evidence accumulated over the last several decades.

Review: Magnesium Deficiency Effects on Bone

Abstract

Skeletal and hormonal effects of magnesium deficiency.

Magnesium (Mg) is the second most abundant intracellular cation where it plays an important role in enzyme function and trans-membrane ion transport. Mg deficiency has been associated with a number of clinical disorders including osteoporosis. Osteoporosis is common problem accounting for 2 million fractures per year in the United States at a cost of over $17 billion dollars. The average dietary Mg intake in women is 68% of the RDA, indicating that a large proportion of our population has substantial dietary Mg deficits. The objective of this paper is to review the evidence for Mg deficiency-induced osteoporosis and potential reasons why this occurs, including a cumulative review of work in our laboratories and well as a review of other published studies linking Mg deficiency to osteoporosis. Epidemiological studies have linked dietary Mg deficiency to osteoporosis. As diets deficient in Mg are also deficient in other nutrients that may affect bone, studies have been carried out with select dietary Mg depletion in animal models. Severe Mg deficiency in the rat (Mg at <0.0002% of total diet; normal = 0.05%) causes impaired bone growth, osteopenia and skeletal fragility. This degree of Mg deficiency probably does not commonly exist in the human population. We have therefore induced dietary Mg deprivation in the rat at 10%, 25% and 50% of recommended nutrient requirement. We observed bone loss, decrease in osteoblasts, and an increase in osteoclasts by histomorphometry. Such reduced Mg intake levels are present in our population. We also investigated potential mechanisms for bone loss in Mg deficiency. Studies in humans and and our rat model demonstrated low serum parathyroid hormone (PTH) and 1,25(OH)(2)-vitamin D levels, which may contribute to reduced bone formation. It is known that cytokines can increase osteoclastic bone resorption. Mg deficiency in the rat and/or mouse results in increased skeletal substance P, which in turn stimulates production of cytokines. With the use of immunohistocytochemistry, we found that Mg deficiency resulted in an increase in substance P, TNFalpha and IL1beta. Additional studies assessing the relative presence of receptor activator of nuclear factor kB ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG), found a decrease in OPG and an increase in RANKL favoring an increase in bone resorption. These data support the notion at dietary Mg intake at levels not uncommon in humans may perturb bone and mineral metabolism and be a risk factor for osteoporosis.

Rude RK, Singer FR, Gruber HE
J Am Coll Nutr Apr 2009
PMID: 19828898

Review: Vitamin A Increases Fracture Risk at 2x Recommended Intake

Abstract

Vitamin A intake and osteoporosis: a clinical review.

If osteoporosis is linked with vitamin A (Vit A) A consumption, millions of people could be affected. A MEDLINE search was performed with keywords retinol, beta-carotene, and osteoporosis. Of 20 clinical studies, 3 were randomized controlled trials (RCTs), 14 were observational studies, and 3 were case reports. Most (8) observational studies were cross-sectional. Oral retinoyl palmitate (RP) in high doses induces fractures and radiographic osteoporosis in animals. Retinol intake from diet or supplements is negatively associated with lumbar, femoral neck, and trochanter bone mineral density (BMD). There is a graded increase in relative risk of hip fracture with increasing retinol intake, attributable primarily to retinol (either from diet or supplements) but not beta-carotene intake. Higher serum retinol levels are associated with higher risk of any fracture and with higher risk of hip fracture, whereas there is no evidence of harm associated with beta-carotene intake. The few RCTs involve serum markers of bone metabolism, not bone density or fracture outcomes. Observational studies are generally consistent in finding harm from either dietary or supplemental retinol intake on BMD and hip fracture risk. Total Vit A intake is more important than source in determining harm. Adverse effects may occur at a level of retinol intake that is only about twice the current recommendation for adult females.
It is not yet possible to set a specific level of retinol intake above which bone health is compromised. Pending further investigation, Vit A supplements should not be used with the express goal of improving bone health.

Crandall C
J Womens Health (Larchmt) Oct 2004
PMID: 15671709

The recommended dietary allowance (RDA) for Vitamin as preformed Vitamin A (Retinol Activity Equivalents) is 700 mcg (or 2,333 IU). This article suggests that twice that, or 4666 IU, increases fracture risk.

Review: Optimal Treatment may Include Both Anabolic and Antiresorptive Treatments

Abstract

Future directions in osteoporosis therapeutics.

Future directions in osteoporosis treatment will include development of medications with increasingly precise mechanistic targets, including the RANK-ligand pathway, cathepsin K inhibition, and Wnt signaling manipulation. More gains are likely with anabolics and newer antiresorptives that cause little or no suppression of formation. Optimal treatment of osteoporosis may require coordination of anabolic and antiresorptive treatment, following stimulation of bone formation with consolidation and long-term maintenance. Some well-established drugs may be useful in such regimens. We can also anticipate emphasis on cost containment using currently available drugs, especially as they become generic. Effective implementation and treatment continuity will be important themes.

Bone H
Endocrinol. Metab. Clin. North Am. Sep 2012
PMID: 22877435