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Nutritional Influences on Bone Health: 8th International Symposium

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Abstract

Nutritional Influences on Bone Health presents a collection of papers from the 8th International Symposium on Nutritional Aspects of Osteoporosis, the primary forum for and only regular meeting exclusively devoted to the topic of nutritional influences on bone health. The outcome is a fusion of the most current and up-to-date research in this area. Key themes include the permeation of the Western diet across the globe, calcium, vitamin D and acid-base balance. Written by authorities on the impact of nutrition on bone health, Nutritional Influences on Bone Health brings the reader the emerging trends, new messages and the latest scientific data in the field, to inform future research and clinical practice. This comprehensive, well researched volume is an essential reference for professionals in the field of bone health and nutrition.

Chapters (36)

Aging is accompanied by a chronic low-grade systemic inflammation state, characterized by an increase in circulating levels in inflammatory mediators, that has been strongly implicated in the pathophysiology of common chronic diseases, including osteoporosis and fractures, sarcopenia, and disability. While a range of genetic, hormonal, environmental, and lifestyle factors have been reported to contribute to increased levels of inflammation, various dietary patterns, foods, and nutrients have also been reported to have anti-inflammatory effects, particularly in people with chronic diseases characterized by increased inflammation such as cardiovascular disease, type 2 diabetes, and cancer. With regard to musculoskeletal and functional outcomes, the findings from cross-sectional and prospective studies and randomized controlled trials on the effects of dietary/supplemental calcium, vitamin D, protein, vitamin K, omega-3 fatty acids, or their combination or food products such as dairy on markers of inflammation are mixed. Currently there is little or no evidence that these nutrients or foods attenuate circulating inflammatory cytokines in healthy middle-aged and older adults. In contrast, in people with chronic disease and/or increased inflammation, including those with osteoporosis and sarcopenia, a limited number of human intervention trials, mostly conducted over 12–16 weeks, have reported that calcium-vitamin D supplementation, high-dairy diets, and increased dietary protein, vitamin K, or omega-3 fatty acids alone or in combination with resistance training can produce modest reductions in inflammation. Whether these short-term reductions in inflammatory markers are clinically important and translate into positive effects on muscle and bone health and function or reduced disability remains unknown. Further randomized controlled trials in older adults and the elderly with or at increased risk of chronic disease are needed to evaluate the long-term efficacy of different nutrients or combination of nutrients and dietary interventions on markers of inflammation and their relation to musculoskeletal health outcomes.
Examination of combinations of foods, as described by dietary patterns in relation to health indices, may be an important approach to further our understanding of chronic disease prevention. Bone loss is a common factor in many chronic inflammatory conditions, although it is unclear whether low-grade systemic inflammation may have similar long-term effects. In this chapter we summarize current evidence relating dietary patterns and chronic low-grade systemic inflammation to bone health. Consideration is then given to potential mechanisms whereby dietary eating patterns may affect inflammatory status. Dietary patterns rich in fruits and vegetables consistently appear to have a protective effect on bone mineral density, likely due to their abundance of micronutrients, minerals, and bioactive compounds. Current evidence relating low-grade systemic inflammation to indices of bone health is limited and contradictory, although modification of dietary eating habits (increasing intakes of plant-based foods and reducing the omega-6 to omega-3 fatty acid ratio) may be important in the management of chronic inflammatory status. Longitudinal studies assessing dietary patterns in relation to bone mineral density/fracture incidence and biomarkers of inflammation could further our understanding of these complex interactions.
The prevalence of overweight and obesity continues to be a major public health concern worldwide. Obesity is a major risk factor for the development of type II diabetes, cardiovascular disease, and increased mortality. Concerns about obesity and overweight among older adults have been far more controversial. The association of overweight and obesity with increased disease burden persists in older adults, and overweight and obesity are also strongly associated with the development of physical disability in this population. However, the efficacy for treatment of obesity in older adults remains an open debate. For obese older adults, who may require weight loss to reduce the risk of cardiometabolic syndrome, weight loss may not be recommended as the associated loss of bone and muscle could leave these individuals at higher risk for frailty and fracture. Thus, optimal strategies for reducing fat mass while preserving bone and muscle mass need to be further evaluated. This chapter will first review the usual age-related changes in skeletal muscle and bone mass with advancing age, the controversy surrounding intentional weight loss in older adults, and discuss the role of diet and physical activity interventions for the successful loss of body fat with specific reference to their effects on bone and skeletal muscle.
Obesity is associated with alterations in several endocrine factors, some of which are involved in regulating bone metabolism. The higher serum concentrations of parathyroid hormone (PTH), estradiol, pancreatic hormones, and adipokines such as leptin, resistin, and cytokines and the lower 25-hydroxyvitamin D (25OHD) have specific actions on the skeleton and regulate cortical and trabecular bone differently. Recent evidence suggests that bone quality is altered in obesity with a higher trabecular volumetric bone mineral density (vBMD), while cortical vBMD is lower. Also, the obese are at greater risk of fracture for a given BMD compared to normal weight individuals supporting the evidence that bone quality is altered due to excess adiposity. Higher concentrations of serum PTH have a catabolic effect on cortical bone and may play a role in reducing cortical vBMD in obesity. The lower serum 25OHD, higher leptin and resistin, and lower adiponectin may also independently contribute to the lower cortical vBMD in obesity. There is little evidence to show that higher pancreatic hormones and cytokines influence trabecular and cortical bone in obesity. The altered hormonal milieu in obesity is one important factor that explains bone architectural changes that occur due to excess adiposity. However, other factors such as diet, genetic factors, altered mechanical loading, and/or other environmental factors may also contribute to bone quality and site-specific fracture risk in obesity.
Late adolescence and early adulthood are times of major behavioral transition in young women as they become more independent and make choices about lifestyle that will affect their long-term health. We prospectively evaluated nutritional and lifestyle factors in 566 15 30-year-old female twins participating in a mixed longitudinal study of diet and lifestyle. Twins completed 790 visits including questionnaires and measures of anthropometry. Nonparametric tests (chi-square, Mann-Whitney U, and Kruskal-Wallis; SPSS) were used to examine age-related differences in selected variables. Dietary calcium intake by short food frequency questionnaire was relatively low [511 (321,747)] mg/day (median, IQR; 60 % of estimated daily total) and did not vary significantly with age. The number of young women who reported ever consuming alcohol (12+ standard drinks ever) increased from 50 % under 18 years to 93 99 % for the 18+ age groups. Of those who consumed alcohol in the preceding year, monthly intake doubled from under 18 years (5.7, 3.9, 19.0 standard drinks; median, IQR) to 18+ years (12.0, 4.7, 26.0; P < 0.001) with the highest consumers being 21 23 and 27 29 years. At age 15 17 years, 14 % reported ever smoking and by age 27–29, 51 % had smoked (P = 0.002). Under the age of 20 years, average cigarette consumption in smokers was six cigarettes per day, increasing to ten above age 20 (P < 0.001). Participation in sporting activity decreased with age (P < 0.001): 47.5 % of 15–17-year-olds undertook 4 or more hour/week of sport, compared with 23.5 % at age 27–29 years. Conversely, sedentary behavior increased with age: 25.0 % of 15–17-year-olds reported 1 or less hour/week of exercise compared with 50.0 % at age 27–29 years. BMI increased with age (P = 0.011), from 21.3 (19.5, 23.6; median, IQR) in the youngest to 23.1 (21.5, 25.9) in the oldest. These highly significant changes in behavior in young women as they transitioned into independent adult living are predicted to impact adversely on bone and other health outcomes in later life. It is crucial to improve understanding of the determinants of these changes and to develop effective interventions to improve long-term health outcomes in young women.
Sarcopenia is the age-related loss of muscle mass and strength, and the consequences include the loss of physical function leading to frailty and disability and to an increased risk of falls and therefore fractures and also mortality. Although age-related muscle loss starts at the age of 30 years, the causes are not yet well established. Fat could influence muscle mass through its integral association with muscle metabolism and influence on myocellular membrane composition or indirectly through its effects on inflammation and insulin resistance. However, the association between the fat composition of the diet and the skeletal muscle mass has not been previously investigated in a general population. Therefore, we investigated this in 2,689 female twins aged 18–79 years calculated using a Food Frequency Questionnaire (FFQ). Body composition was measured using dual-energy X-ray absorptiometry, and indexes of skeletal muscle mass, fat-free mass (FFM), and fat-free mass index (FFMI, weight/height2) were calculated according to quintile of dietary fat and also adjusted for covariates. Associations per quintile were compared with 10 years of age. FFM and FFMI were significantly and positively associated with the P:S ratio and inversely associated with total fat, saturated fatty acids, monounsaturated fatty acids, and trans-fatty acids, as a percentage of energy. Comparisons of quintile associations versus those of 10 years of age ranged from 72 % for FFM for the P:S ratio to 95 % for total dietary fat. Both dietary total fat load and fatty acid composition were associated with skeletal muscle mass. Although the scales of the associations were relatively small, they were significant after multivariate adjustment. These novel findings are suggestive that a fat profile that is already associated with CVD protection may also be beneficial for conservation of skeletal muscle mass.
We urgently need public health strategies to help with the prevention of poor bone health across the age ranges. It is especially useful to focus attention on factors that are amenable to change, with nutrition and exercise having clear potential. The aim of this chapter is to review the current evidence for a role of acid–base homeostasis in bone. Analysis of existing literature enabled a combination of observational, clinical, and intervention studies to be assessed in relation to dietary alkalinity, dietary acidity and bone health. Mechanisms of action for a dietary alkalinity “component” effect were examined, and the role that fruit and vegetables can play in bone health was addressed. Natural, pathological, and experimental states of acid loading/acidosis have been associated with hypercalciuria, and negative calcium balance and, more recently, the detrimental effects of “acid” from the diet on bone mineral have been demonstrated. At the cellular level, a reduction in extracellular pH has been shown to enhance osteoclastic activity directly, resulting in increased resorption pit formation. A number of observational, experimental, clinical, and intervention studies have suggested a positive link between fruit and vegetable consumption and the skeleton. Further research is required, particularly with respect to the influence of dietary manipulation using alkali-forming foods on fracture prevention. There remain no long-term Dietary Approaches to Stop Hypertension (DASH) on bone health in younger and older age cohorts, and this is urgently required. Should the findings of the DASH/fruit and vegetable studies prove conclusive, a “fruit and vegetable” approach to bone health maintenance may provide a very helpful strategy for bone health development and maintenance throughout the life cycle.
Potential metabolic influences of dietary acid load on bone health have been discussed controversially. Here, we review the available findings in adults and healthy children regarding certain methodological aspects including (i) appropriate use of urinary biomarkers – potential renal acid load (PRAL) and net acid excretion (NAE), (ii) problems in the interpretation of results on calcium balance and bone turnover markers, and (iii) possible influences of selection bias regarding baseline diets of the population groups of randomized controlled trials. Based on the available evidence, it is concluded that calcium balance measurements and bone turnover markers are no adequate and sensitive tools to evaluate the modest but long-term prevailing influence of nutrition on bone status. Findings in children and adults exclusively conducted on the most reliable outcomes, that is, bone densitometric structure analyses, suggest that a low-PRAL diet may be especially relevant in certain population groups, for example, in children with higher dietary protein intakes, in postmenopausal women with impaired bone status, and probably in adults on a habitually acidifying nutrition. The mechanisms mediating detrimental bone effects of higher dietary acid loads under discussion include changes in endocrine–metabolic milieu, for example, impairment of GH/IGF-1 axis and higher glucocorticoid secretion as well as direct bone–cell-related changes by higher acid load. In conclusion, to identify moderate alterations in bone status exerted through nutritional influences, not only appropriate assessments of dietary proton load but also outcome measurements that are closely related to long-term bone structure are required.
Diets in industrialized nations are no longer based predominately on potassium rich fruit and vegetables, resulting in substantially lower potassium intakes as well as the alkaline anions such as bicarbonate and citrate that accompany potassium in fruit and vegetables. The reduction in potassium and alkali intake while maintaining adequate dietary protein intake leads to an imbalance between the acid producing and the base producing components of the diet. This dietary net acid load is theorized to require mobilization of skeletal base to aid in acid neutralization, leading to ongoing skeletal resorption to maintain systemic acid base homeostasis. Short-term calcium balance studies suggest that supplementing the diet with alkaline potassium salts lowers urine calcium losses with no increase in stool calcium, resulting in a net improvement in calcium balance. The majority of studies examining potassium supplements also suggest bone resorption is reduced by potassium citrate or bicarbonate. However, not all studies show a reduction in bone turnover and the two existing bone density trials provide conflicting results. In particular, controversy remains over whether the benefits to calcium metabolism demonstrated in the short-term calcium balance studies persist. To address this controversy, we conducted a randomized, placebo controlled trial in 52 men and women (mean age 65.2 + 6.2 years) who were randomly assigned to potassium ­citrate 60, 90 mmol, or placebo daily with measurements of bone turnover markers, net acid excretion, and calcium metabolism including intestinal fractional calcium absorption and calcium balance at baseline and 6 months. At 6 months, 24-h urine calcium was significantly reduced in both potassium treatment groups and fractional calcium absorption was not changed by potassium citrate supplementation. In subjects randomized to potassium citrate 90 mmol/day, net calcium balance was significantly improved compared to placebo. Serum C-telopeptide, a marker of bone resorption, decreased significantly in both potassium citrate groups compared to placebo, while bone specific alkaline phosphatase did not change. Our study supports the hypothesis that supplementation with alkaline potassium salts such as potassium citrate has the potential to improve skeletal health. Studies with definitive outcomes such as bone density and fracture are needed.
Background: Sufficient calcium intake is essential for the maintenance of bone health in older people. However, the effect of dietary protein on bone mass of older women has been controversial. To the best of our knowledge, there has been no clinical trial evaluating the effect of protein supplementation on bone mass in older Chinese women. Objective: To evaluate the effect of 1-year protein and calcium supplementation on bone mass in older Chinese women compared to calcium supplementation alone. Design: A 1-year randomized controlled trial was conducted in 283 Chinese postmenopausal women aged 68.1 ± 0.5 years (range 60–86 years). Study participants were randomized to receive either protein powder containing 30 g soybean protein and 1,000 mg calcium as calcium carbonate (Pro + Ca group, n = 142) or only 1,000 mg calcium per day (Ca group, n = 141). Measurements performed include dietary intakes by 1-year food-frequency questionnaire, physical activity by International Physical Activity Questionnaire (IPAQ)-Short Form, and areal bone mineral density (aBMD) at hip, lumbar spine (L2–L4), and total body by DXA at baseline and 1 year later. Results: There were no significant differences between the two groups in baseline characteristics. With supplementation, both groups had significantly higher calcium intake compared to the baseline (1,647 ± 53 mg/day vs. 879 ± 30 mg/day, P = 0.01), and the average dietary protein intake was significantly higher in the Pro + Ca group compared to the Ca group (107.8 ± 4.6 g/day vs. 75.7 ± 3.1 g/day, P < 0.001). After 1-year supplementation, there was a slight but significant increase in aBMD at total body, femoral neck, trochanter, and total hip in both groups after adjusting for baseline age, BMI, calcium intake, physical activity level, and serum 25(OH)D level (time effect, all P < 0.05). There were no significant time effects on lumbar spine aBMD in either group. The Pro + Ca group had significantly greater increase in total-body aBMD (9.5 mg/cm2) compared to the Ca group (0.4 mg/cm2) after 1 year of supplementation before adjustment for covariates (time × group interaction, P < 0.05). There were no significant effects of protein supplementation on aBMD of other sites. Conclusion: Higher intake of dietary protein might have a positive effect on total-body bone mass in Chinese postmenopausal women when calcium intake is sufficient.
The interdependent influence of the protein and the calcium intake on bone health has been conclusively studied. For obtaining a positive bone effect from nutritional protein, an adequate calcium intake is required, and vice versa. A high-protein intake was first considered as potentially negative for bone, but this fear was not defendable anymore when it became evident that a high-protein intake increases urinary calcium excretion because it stimulates calcium absorption. Protein deficiency was shown to be detrimental to bone, not a high-protein intake. However, some large follow-up studies demonstrated that the combination of a high-protein intake with a low-calcium diet increases fracture risk. This particular nutritional profile seems to be rare, but some cross-sectional studies seem to confirm that.
Improvement of peak bone mass in younger age and reducing bone loss in aging are two strategies to reduce the risk for developing osteoporosis. Modulating intestinal calcium absorption by modifying the diet can contribute to improvement of bone mass, and reduction of inflammation during menopause can help reduce the risk of bone loss. Calcium absorption takes place via an active process in the duodenum, modulated by active vitamin D, or by passive paracellular absorption that can take place throughout the intestine. Prebiotics are nondigestible carbohydrates which promote bacterial growth in the colon. Fermentation by the bacteria results in the production of organic acids which reduce the pH in the large intestine and may improve solubility of minerals increasing passive diffusion via the paracellular pathway. Increased cell proliferation and hypertrophy of the colon wall have also been reported, while some authors also report increased expression of calbindin-D9k, the protein responsible for carrying calcium through the intestinal cell. While the mechanism by which probiotics improve calcium absorption has not been proven, it is possible that the mechanism is similar to that of the prebiotics. Another dietary component that can affect intestinal calcium absorption is long-chain polyunsaturated fatty acids (LCPUFA). These have been shown to improve calcium absorption by modulating the action of vitamin D in the intestine, modulating intestinal membrane composition and thereby increasing activity of the membrane pumps responsible for transport of minerals across the basolateral membranes. The omega 3 LCPUFAs also have specific effects on bone cells and reduce inflammation which may be of benefit to bone especially during menopause. In addition, LCPUFAs may have a prebiotic effect, modulating gut microflora. The possible contribution of these dietary components to calcium absorption and bone maintenance in rats and younger as well as older adults is presented.
Dietary compounds from natural products are the subject of investigation for their beneficial effects on bone. Natural products may be safer and better tolerated by consumers than current therapies for treatment of osteoporosis. Soy isoflavones have been the most studied but results are mixed. Whole soy food consumption in Asian women is associated with reduced fracture incidence in observational studies. However, purified isolated soy isoflavones in randomized controlled trials in postmenopausal Western women are not protective of bone loss. Polyphenolic compounds in plum and berries have both anabolic effects and the ability to suppress bone resorption. These effects occur through antioxidation and anti-inflammatory cell signaling pathways. Rapid screening approaches using urinary excretion of calcium tracers from labeled bone can be used to compare doses and types of natural products for their effect on bone calcium balance.
Flavanones are a class of flavonoids found mainly in citrus fruits, the most common ones being hesperidin and naringin. These compounds exist as glycoside conjugates in the fruits at relatively abundant concentrations. Despite the extensive metabolism, the flavanones circulate in blood in the low μM range, which we therefore consider as the “physiological” concentration as opposed to more pharmacological concentrations (50–100 μM) often used in cell culture studies. Among the various biological effects attributed to the flavanones, the more consistent ones are anti-inflammatory and lipid-lowering properties. In particular, the anti-inflammatory effects of the flavanones have been shown to be mediated through the inhibition of the NF-κB pathway. Concerning the effects of flavanones on bone metabolism, the in vivo evidence in preclinical studies mimicking postmenopausal or senile bone loss shows an effect of hesperidin on preservation of bone mineral density (BMD) associated with reduced collagen breakdown. In the first placebo-controlled, randomized, double-blind clinical trial to be performed on the ability of hesperidin (500 mg daily for 2 years) to attenuate bone loss in postmenopausal women, we found that hesperidin did not significantly alter the 1–2 % BMD loss/year generally observed in this population. However, the subjects consuming hesperidin presented a better balance in bone metabolism as reflected by the bone turnover index. Any nutritional approach to bone health should include the main bone micronutrients (calcium, vitamin D) already shown to improve BMD in osteopenic situations. However, further bioactive nutrients in the diet, such as the flavanones, may play a further role in modulating bone turnover and help protect against bone loss in at-risk populations. The question remains as to how best to measure such effects and show their relevance to bone quality, whether it is via bone biomarkers, bone architecture, or bone ­mineral density in combination or not with calcium and vitamin D.
Experimental evidence has implicated that homocysteine and oxidative stress may be involved in the pathogenesis of osteoporosis. In accord, observational studies among Caucasian populations have also suggested that homocysteine-related B vitamins (vitamins B2, B6, B12, and folate) and carotenoids with antioxidant functions may be beneficial to bone health and therefore protect against osteoporotic fractures. Incidence of hip fracture is rising in Asia, but there is paucity among Asian populations on dietary factors. We prospectively examined the associations of dietary intakes of B vitamins and carotenoids with hip fracture risk among elderly Chinese in the Singapore Chinese Health Study. Cox proportional hazards model was applied to determine the strength of association after adjusting for potential confounders. Our results showed a dose-dependent inverse relationship between vitamin B6 intake and hip fracture risk among women (p for trend = 0.002). Conversely, no protective association was found in men. Dietary intakes of vitamins B2, B12, and folate were not related to hip fracture risk in either gender. Vegetables are main sources of carotenoid intake in this population. In men, we found a dose-dependent inverse relationship between consumption of total vegetables and hip fracture risk (p for trend = 0.004). Similarly, higher intakes of total carotenoids, α- and β-carotene, were associated with lower hip fracture risk in men (all p for trend <0.05). Consumption of vegetables or carotenoids did not show an association with hip fracture risk in women. The gender-specific results in the protective roles of dietary B vitamins and carotenoids suggest that the mechanistic pathway for osteoporosis may be different between men and women.
There is evidence to suggest that fruit and vegetable consumption is beneficial for bone health. Anthocyanins are bioactive flavonoid compounds found mostly in fruits, particularly berries, some vegetables, and wine. A diet rich in anthocyanidins is thought to have multiple health benefits, and recent studies have shown that high intakes of anthocyanidins are associated with markers of bone health. However, much is still unknown about the variation in composition of anthocyanidins in foods worldwide, and therefore it is difficult to quantify dietary intakes with certainty. To date there have been no human intervention studies looking at anthocyanidins in relation to bone health, but anthocyanidin-rich dried fruits have shown positive effects on markers of bone health in both human observational and animal studies. The metabolism, bioavailability, and absorption of anthocyanidins vary greatly between people, partly due to differences in gut microflora which metabolizes anthocyanidins into products such as phenolic acids. However, the processes involved with the metabolism, bioavailability, and absorption of anthocyanidins are not fully understood. Cellular studies have shown that it is the anthocyanidin metabolites and not the intact anthocyanidins that affect osteoblast differentiation. Neither anthocyanidins nor their metabolites have been studied directly on osteoclasts in vitro. Preliminary data suggests that an anthocyanidin-rich diet may have positive effects on bone health which may in future have consequences for dietary guidelines. However, much is still to be investigated in this area particularly with regard to metabolism and cellular mechanism of action. An intervention study quantifying the effects of anthocyanidins on markers of bone health is recommended. This chapter explores the current evidence for the role of anthocyanidins in bone health.
This chapter evaluates differences between oral supplementation with calcifediol (25-hydroxyvitamin D) and vitamin D3 (cholecalciferol). Oral supplementation with calcifediol results in an immediate and sustained increase in serum 25-hydroxyvitamin D concentrations. This may be relevant in clinical care as higher circulating level of 25-hydroxyvitamin D can be reached much faster than on the standard supplementation with vitamin D3. However, whether calcifediol has additional benefits superior to vitamin D3 will need further investigation in an equivalent dose comparison trial.
Vitamin D status is associated with muscle strength, physical performance, and falls as has been observed in many epidemiological studies. When serum 25-hydroxyvitamin D increases from very low levels to 50 nmol/l, physical performance increases and plateaus with higher levels of serum 25(OH)D. Randomized controlled clinical trials were performed with vitamin D alone or with vitamin D and calcium with the endpoint falls. Eight of thirteen studies showed a significant decrease of fall incidence, and in six of seven significant double-blind studies, vitamin D was combined with calcium and compared with double placebo. The decrease of fall incidence ranged from −19 to −70 %. One study with vitamin D3 dose of 500,000 IU once per year showed an increased fall incidence in the vitamin D group compared with the placebo group. The increased fall incidence was observed in the first 3 months after the high vitamin D dose. Eight meta-analyses have been performed on the effects of vitamin D on fall incidence. One may conclude from these that vitamin D3 is effective in doses of 800 IU/day or more and preferably combined with calcium. Vitamin D may influence muscle strength through genomic and non-genomic pathways. The active metabolite 1,25-dihydroxyvitamin D binds to the nuclear vitamin D receptor and can activate more than 300 genes, and it may also bind to a membrane receptor thus activating second messengers leading to fast calcium influx. Vitamin D may influence muscle fiber proliferation and differentiation, and calcium influx and calcium transport to the sarcoplasmic reticulum. There is still some debate on the presence of the vitamin D receptor in human muscle tissue because it was demonstrated by some but not by other investigators. In conclusion, vitamin D can influence muscle strength, balance, and prevent falls.
Introduction: Vitamin D deficiency is a global health problem. Limited skin exposure to sunlight, obesity, and low dietary calcium intake may all impact vitamin D status and bone health. The aims of this study were to determine vitamin D status and its association with the extent of veiling and different measures of obesity and to examine the impact of milk intake on vitamin D status and bone metabolism markers in a sample of randomly selected pre- and postmenopausal healthy Saudi women. Methods: A total of 449 women were studied. Fasting blood samples were collected for assessment of 25(OH)D status and carboxy-terminal telopeptide of type I collagen (CTX). Anthropometric parameters and total body fat (TBF) by dual-energy X-ray absorptiometry were measured. Milk intake was determined using a validated food frequency questionnaire. Results: A total of 85.5 % of women had vitamin D deficiency with a serum level <50 nmol/L. Women who were completely covered (both face and hands or face only) (n = 261) were found to have a significantly lower 25(OH)D status than women who covered their heads, but not their faces and hands (n = 188) [26.5 ± 19.6 nmol/L vs. 32.0 ± 24.4 nmol/L], respectively (P < 0.011). A significant negative correlation between 25(OH)D and body mass index (BMI) (r = −0.203, P < 0.01), TBF (r = −0.340, P < 0.01), and waist circumference (WC) (r = 0.140, P < 0.05) was found in the postmenopausal women. A positive correlation was found between milk intake and 25(OH)D status, which remains significant after controlling for BMI and age (r = 0.193, P < 0.001). A trend for milk intake to be negatively associated with CTX excretion was also observed (r = −.083, P ≤ 0.07) after adjustment for age and BMI. Conclusion: Vitamin D deficiency is rather highly prevalent among healthy Saudi women. Further investigations are currently under way to explore ­concomitant effects of these factors on bone density in this population.
Peak bone mass (PBM) is mostly determined by genetics, but lifestyle and diet during youth may modify the final PBM. We examined changes in spine and hip bone mineral density (BMD) in a cohort of 146 males entering the US Military Academy (average age = 18.8 ± 1.1), randomly sampled from the full sample (755 males). Calcium intake was determined by a brief food frequency questionnaire. Serum 25(OH)D was measured by DiaSorin RIA, and intact (1–84) PTH was measured using the Elecsys (Abbott) on a single serum sample. BMD at the lumbar spine and total hip were measured at baseline and annually for 4 years by DXA (Lunar DPX-IQ). Hip structural analysis (HSA) was done using the methodology of Yoshikawa (JBMR 1994). Slopes of change in spine and hip BMD and HSA parameters were determined for each male. Average calcium intake was 1,803 mg/day (range 387–6,258). There was no significant use of calcium or vitamin D supplements. Men with calcium intake <800 mg lost 1 % of total hip BMD per year, whereas those with calcium intakes >800 mg a day gained 0.23 % BMD per year (p < 0.007), even after controlling for race and serum 25(OH)D. There was no relationship with change in spine BMD and calcium intake. Males with serum 25(OH)D level >20 ng/ml had a greater increase in hip BMD (0.2 % gain in hip BMD/year) as compared to a 0.3 % hip BMD loss per year in the 25(OH)D < 20 ng/ml group. Serum vitamin D was also correlated with hip cross-sectional area. Both relationships with 25(OH)D persisted after controlling for race and BMI (p < 0.03). However, there was no relationship between serum 25(OH)D and change in spine BMD. We conclude that in physically active college-aged men, dietary calcium intake and vitamin D status may modify peak bone mass acquisition.
At present, there appears to be a degree of controversy regarding the comparative effectiveness of vitamin D2 and D3 in raising and maintaining serum 25-hydroxyvitamin D (25(OH)D) levels. It was previously believed that the two vitamers were comparable in metabolic function; however, it is now known that when comparing vitamin D2 to D3, there are a small number of structural differences in the molecular makeup of these vitamers. Thus, the area of “vitamin D2 versus vitamin D3” research is expanding and exploring the possible mechanistic pathways that may highlight a clear and quantifiable difference between vitamin D2 and D3 that could have far-reaching consequences for both future vitamin D research and public health policy alike. With this in mind, a recent meta-analysis of the current research available has shown that while the majority of data appear to support the conclusion that vitamin D3 appears to be more efficacious than D2, this does not always translate across all studies. Therefore, this review explores the studies involved, the possible mechanism behind the reported differences between vitamin D2 and D3, and the need for future research.
Abbreviations 25[OH]D 25-hydroxyvitamin D 1,25[OH] 2 D 1,25dihydroxyvitamin D iPTH Intact parathyroid hormone Abstract Because a signi fi cant number of children and adolescents worldwide are considered vitamin D insuf fi cient or de fi cient, skeletal health may be compromised leading to long-term fracture risks. For this reason, a heightened research priority has been placed on the role of vitamin D in bone metabolism during growth. Vitamin D supplementation increases 25-hydroxyvitamin D (25[OH]D) in children and the response appears to be dose-dependent, though dose–response trials are needed to con fi rm this. Increases in serum 1,25 dihydroxyvitamin D (1,25[OH] 2 D) and decreases in intact parathyroid hormone (iPTH) occur with vitamin D supplementa-tion, and these responses are more pronounced with higher doses of vitamin D and in populations considered vitamin D insuf fi cient and de fi cient (<50 nmol/L). In vitamin D-suf fi cient groups (>50 nmol/L), iPTH suppression is minimal. The effect of vitamin D supplementation on biochemical markers of bone turnover likely depends on basal 25(OH)D concentrations and doses of vitamin D administered, with lower baseline 25(OH)D and higher vitamin D doses promoting more favorable responses, respectively. Because there is a dearth of knowledge with respect to race differences in vitamin D and bone metabolism, dose–response trials among multiple race and ethnic groups are needed. Keywords Vitamin D • Supplementation • 25(OH)D • 1,25(OH) 2 D • iPTH • Bone turnover • Children
Supplemental vitamin D is now widely recommended, but little guidance is provided on how or when to take vitamin D supplements. The process of vitamin D replacement is complicated by the fact that the increment in 25-hydroxyvitamin D (25OHD) in response to a given dose varies greatly from person to person. This chapter will examine the factors associated with the 25OHD response to supplementation with vitamin D, including genetic determinants, the starting 25OHD level, body mass index, and gastric acid production. It will also consider the effects of a meal and of meal composition with respect to cholesterol and phytosterol intake and the amount and type of dietary fat on the 25OHD response to supplementation.
A lack of vitamin D leads to a number of adverse health outcomes, and the most widely accepted is an increased risk of osteoporotic fracture. A number of national surveys have shown that 25 hydroxyvitamin D (25OHD) concentrations, the best indicator of vitamin D status, are below even conservative cutoffs for sufficiency (<50 nmol/L). Strategies are needed to improve vitamin D status. Sunlight exposure is an important contributor to vitamin D status; however, at higher latitudes during the winter and in populations that do not receive adequate sunlight exposure for various reasons, an exogenous source of vitamin D is required. Vitamin D intake from natural food sources is low in most populations. Furthermore, supplementation, although effective and very important as method to combat vitamin D insufficiency, will not work for the entire population. Vitamin D fortification does improve vitamin D intakes and status of populations, but a greater range of food vehicles and/or greater amounts of vitamin D may be necessary to improve vitamin d status.
The standard model for regulation of calcium absorption identifies ­calcitriol as the vitamin D metabolite responsible for active transport of calcium across the intestinal mucosa, with 25-hydroxy vitamin D [25(OH)D] functioning as the substrate for renal synthesis of calcitriol. However, as experience with measurement of calcium absorption has accumulated, it has become evident that (1) calcitriol is sometimes ineffective in elevating calcium absorption and (2) 25(OH)D is sometimes effective, apparently in its own right. Additionally, supplemental administration of vitamin D or 25(OH)D sometimes increases calcium absorption, and sometimes does not. A new model that integrates the growing number of seemingly contradictory observations is needed. Missing in the current model is the fact of calcium need, which helps to explain many of the discrepancies. Finally, the apparent cooperation of 25(OH)D and 1,25(OH)2D may be explainable by sequential binding of both metabolites to different pockets of the vitamin D receptor.
Vitamin D insufficiency is a common problem worldwide, with a varying prevalence depending on the population of interest and cutoff used to define insufficiency. The medical literature has witnessed an explosion in the number of vitamin D publications over the last three decades, most convincingly supporting a beneficial effect of vitamin D on musculoskeletal parameters. This led the Institute of Medicine (IOM) to issue an update in 2011 with an increase in the recommended vitamin D intake across all age groups and to set the desirable level at 50 nmol/L. This compares modestly to the desirable level recommended by the Endocrine Society (ES) of 75 nmol/L, which is similar to that recommended by the International Osteoporosis Foundation for older individuals. While the IOM Committee focused on the population needs in North America, the Endocrine Society tried to target high-risk populations. Some of the lowest vitamin D levels are recorded in black subjects and in non-western populations, populations in whom data on fractures and falls are scarce. Information using surrogate markers for the beneficial effect of vitamin D action on musculoskeletal health has many limitations, even in Caucasian subjects where it is the most available. The calcium–vitamin D economy in blacks seems different, and the desirable vitamin D level to optimize musculoskeletal health may be lower than that of Caucasians. Furthermore, some evidence from association studies suggests an increase in the risk of fractures in blacks, and possibly Asians, at 25(OH)D levels exceeding the desirable level for Caucasians. In view of this apparent divergence, the lack of solid outcome data in other ethnic and racial groups, and the multitude of modulators that affect vitamin D metabolism and action, the notion of a global desirable vitamin D level to date is not tenable.
Gender differences in bone during childhood and adolescence are well described in countries with moderate to high calcium intakes; there are few data from countries where children have delayed puberty and low habitual calcium intakes. The aim of this study was to determine whether gender differences in bone and body composition exist in prepubertal Gambian children accustomed to a low calcium intake. Four hundred and forty-seven prepubertal children (216 males, 231 females) were recruited between the ages of 7.8 and 11.9 years. Bone mineral content (BMC) and bone area (BA) were measured at whole body, lumbar spine, and hip using dual-energy X-ray absorptiometry (GE Lunar Prodigy). There were no significant differences between males and females in age, body weight, and height or body mass index. Gender differences existed in BMC and BA both before and after size adjustment. Body composition also differed between males and females. Regular follow-up measurements in these children have commenced to assess whether these differences persist during and after puberty and implications for future bone health.
Osteoporosis is a major public health problem affecting over 200 million people worldwide. The 2010 dietary guidelines for Americans recommend consuming 3 cups/day of fat-free or low-fat dairy products for adults. Although individual nutrients usually found in dairy products may be beneficial for bone health, few studies have directly compared specific types of dairy foods. Yet it has been suggested that dairy foods are not equivalent vehicles of calcium due to their different nutrient profile. While studies of milk intake and bone mineral density (BMD) are plentiful and mostly positive, the evidence for hip fracture risk reduction remains weak. Studies on yogurt intake and bone health have been very few but promising though the role of probiotics in yogurt on bone is unclear. It is unclear how other dairy foods may relate to bone health. Few studies that have examined cheese intake have focused either on intake of total cheese or a specific low-fat variety. High-fat/high-sugar dairy foods like cream and ice cream have low nutrient density and are widely consumed, yet very little is known about their impact on the skeleton. The additive and synergistic role of sodium and saturated fats along with other bone-specific nutrients (e.g., calcium, vitamin D, phosphorus, protein) in cream and cheese is complicated and needs further clarification. Future studies should (i) aim to resolve the disparate findings from BMD studies versus fracture studies on milk intake, (ii) clarify the role of probiotics in calcium absorption and bone health, (iii) focus on the skeletal effects of low-fat cheese and the influence of sodium content of the different cheeses, and (iv) focus on dairy food products instead of single nutrients within dairy while at the same time considering nutrient profiles of specific dairy foods. Overall, the studies that are highlighted in this chapter suggest a significant role for dairy intake in maintaining bone health.
Adolescence presents an opportune time to influence peak bone mass with prebiotic agents like galacto-oligosaccharides (GOS) that increase calcium absorption in the large intestine. Previous literature has helped elucidate the mechanisms by which prebiotics elicit their response which involves decreased luminal pH following bacterial fermentation. In addition to improved mineral absorption, dietary supplementation with GOS in rats has been associated with improved bone mineral content (BMC) during growth, reduced losses of BMC and bone mineral density (BMD) after ovariectomy, and increased cecal content weight. Similar bone-sparing results have been seen in postmenopausal women, while preliminary results in adolescents show that GOS increases fractional calcium absorption. This effect may be mediated by bacterial fermentation in the colon as bifidobacteria content of the feces was increased after GOS consumption. Further work is needed to fully elucidate the intestinal mechanism and understand the long-term effects of GOS consumption.
Background: Although it is widely accepted that dietary calcium intake (CaI) and weight-bearing physical activity (WBA) increase bone mass accrual during growth, few prospective studies have followed children from early childhood to sexual maturity to evaluate this relationship. Aims: To describe the relationship between CaI and WBA and total body bone mineral content (TBBMC) accrual in a large, multiracial cohort of children followed prospectively. Methods: Five US centers recruited 2014 healthy children (ages 5–19 years) and measured them annually for up to 7 years. Subjects with at least two annual visits are included in this analysis (944 boys, 973 girls). Assessments included TBBMC, Tanner stage, WBA, and CaI. Multiple regression was used to model annual increases in TBBMC, controlled for annualized overall height growth, Tanner stages, and baseline TBBMC. The effect of adding WBA and CaI to the model was evaluated for four subgroups: nonblack boys and girls and black boys and girls. Results: WBA had a positive association with adjusted annual increases in TBBMC in all subgroups (p < 0.05), while CaI was positively related to TBBMC increase in nonblack males and nonblack females. Conclusion: These findings support the importance of public health efforts to increase physical activity in children and adolescents while assuring adequate calcium intake.
Falls and fracture rates are high in ambulatory aged care residents, and malnutrition may contribute to falls and fracture risk by influencing bone’s material composition and structure. We aimed to test if a dairy-based protein (10 g/day), calcium (600 mg/day), and vitamin D (960 IU/day) supplement formulated to increase intakes to recommended levels would reduce falls and fracture risk in ambulatory low-level aged care residents. This was a cluster-randomized, single-blind intervention involving 813 residents (mean age 86.1 ± 5.9 years, 76 % female) from 16 low-level aged care facilities in Melbourne, Australia. Twelve months of observation in all facilities was followed by 8 months of food-based supplementation (intervention) or usual intake (controls). Number of fallers and non-vertebral fractures was assessed in all residents, and serum 25(OH)D, PTH, osteocalcin, bone mineral density (BMD) by densitometry, bone structure and volumetric BMD at the distal radius and tibia using high-resolution pQCT, balance (Lord’s balance test), and functionality (timed up and go, walking velocity) were tested in a subset of 84 residents. Repeated measures ANOVA and logistic regression models were used to compare cases and controls. Among the whole sample, supplementation reduced the number of fallers by 42 % (OR = 0.58, 95 % CI: 0.44–0.78, p < 0.001). Among the 58 of 84 participants with follow-up data, supplementation slowed bone loss at the proximal femur, maintained serum 25(OH)D, and reduced PTH by 16 ± 8 %, p < 0.03. Fortifying foods with protein, calcium, and vitamin D reduced falls in ambulatory aged care residents and is an accessible and inexpensive approach to reduce falls and slow the progression of bone fragility in the elderly.
Objectives: Vitamin D deficiency has been linked to hypertension and ­cardiovascular events in observational studies. It is unclear whether vitamin D and/or calcium supplementation can reduce blood pressure, and if so, by how much. Methods: This prospective study was undertaken to test the influence of latitude, seasonal variations, possible threshold effects, and duration of vitamin D efficacy after cessation of therapy. Two hundred and forty-two healthy male and female subjects with a mean age of 77 ± 4 years and a 25-hydroxyvitamin D serum level below 75 nmol/l were recruited in Bad Pyrmont and Graz and were randomly assigned to two treatment groups: one group receiving 1,000 mg calcium per day (Ca) and the other group 1,000 mg calcium and 800 IU vitamin D (Ca + D) over 12 months. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were measured under standardized conditions every 4 months. Statistical evaluation was carried out using the statistics software of IDV, Gauting (Test + Estimation, version 5.2, “CRO” Dr. Heinz and Partner, Vienna, Austria). Results: We performed an intention-to-treat analysis and found the following results: In the (Ca + D) group, 25-hydroxyvitamin D increased significantly (p < 0.01) from 57 ± 20 nmol/l at baseline (BL) to 84 ± 18 nmol/l at month 12 (M12), whereas in the (Ca) group, there was no change (54 ± 19 versus 55 ± 18 nmol/l). In the (Ca + D) group, SBP decreased significantly (p < 0.01) from 134 ± 17 mmHg at BL to 124 ± 14 mmHg at M12, whereas in the (Ca) group, there was no change (137 ± 17 versus 133 ± 16 mmHg). In the (Ca + D) group, DBP decreased significantly (p < 0.01) from 76 ± 7 mmHg at BL to 72 ± 7 mmHg at M12, whereas in the (Ca) group, there was no change (79 ± 8 versus 78 ± 9 mmHg). In the (Ca + D) group, HR decreased significantly (p < 0.01) from 74 ± 4 beats per minute at BL to 70 ± 4 beats per minute at M12, whereas in the (Ca) group, there was no change (74 ± 4 versus 75 ± 4 beats per minute). Conclusion: Despite a relatively high inclusion criterion for vitamin D (75 nmol/l) and independent of latitude, we observed a significant reduction of blood pressure and heart rate after supplementation with vitamin D and calcium. This effect of nutritional supplements may be comparable to the efficiency of antihypertensive drugs.
Hispanics are a growing segment of the US population and will soon comprise one-fourth of the population. Mexican Americans (MA) are the majority of Hispanics in the USA. MA have been reported in some studies to have significant differences in several health outcomes that could impact calcium metabolism. Determining racial differences is imperative as this information can then be used to make racial- and ethnic-specific recommendations for behavior changes to reduce risk of osteoporosis, particularly during adolescence, the period of rapid bone accumulation that accounts for up to half of adult peak bone mass. Calcium intake is critical for adequate bone mineralization and increases in calcium intake result in higher bone mass, which, if sustained, may result in a lower risk of osteoporotic bone fracture later in life. Determining the influence of calcium intake on calcium retention and bone metabolism requires metabolic studies on a range of calcium intakes. Here we describe metabolic studies conducted in MA, white, black, and Asian adolescents while consuming controlled diets with various levels of calcium intakes. Our results showed that Mexican American girls had higher calcium retention compared to white girls but similar to Asians and blacks. However, Mexican American boys had similar calcium retention compared to white, Asian, and black boys. Future work is needed to calculate the minimal calcium intake leading to the maximal calcium retention in this group, kinetic analysis, and multiple regression models to quantify the effects of calcium intake, race/ethnic group, sex, sexual maturity, body composition, and hormonal and bone biomarkers on calcium retention. Our results will allow us to determine if MA adolescents have different calcium needs compared to the other groups studied.
Concern about calcium supplementation causing cardiovascular events can widen the gap between calcium intakes and calcium recommendations. At this time, the association between calcium intake and cardiovascular disease is inconsistent, lacks a plausible mechanism, has no dose–response effect, and is not associated with cardiovascular mortality. In fact, calcium and vitamin D supplementation is systematically associated with decreased all-cause mortality. It is prudent to obtain recommended intakes of three servings of dairy products each day or to include fortified foods or supplements containing 300 mg calcium for every serving of dairy missed in order to meet calcium requirements without exceeding upper levels.
Analyses of all cardiovascular event data available from all trials using calcium supplements alone have demonstrated a significant increase in the risk of myocardial infarction. When data from the Women’s Health Initiative (WHI) is evaluated, the same adverse effect is apparent in those who were not already taking calcium supplements at the time of randomization. Meta-analyses of these WHI data with those of other trials which studied calcium with or without vitamin D confirm that the risk of myocardial infarction is increased by 24 % and that of stroke by 15 % with the use of calcium supplements. While there is not a comparable set of trials using calcium-rich foods as an intervention, observational data do not suggest that dietary calcium is a risk for cardiovascular disease. Therefore, the use of calcium supplements for prevention of osteoporosis is no longer appropriate in most situations, since it causes more adverse events than it prevents. Instead, we should advise our patients as to how they can obtain calcium intakes in the range of 600–1,000 mg/day from a balanced diet.
Research in the field of nutrition allows considering the establishment of a real prevention of osteoporosis. The value of fruits is discussed. Indeed, red fruits are particularly interesting for their high content in anthocyans, endowed with antioxidant and anti-inflammatory properties. Fifty-six postmenopausal women (less than 6 years) aged 50–65 years, without HRT, were included in a controlled, randomized, double-blind placebo, prospective study, after a medical examination and a blood test. Throughout the 3-month study period, they kept their eating habits, limiting however consumption of red fruits. They were randomized into two groups of 28 subjects receiving either 0 or 120 mg of anthocyans daily, from blueberry extract. Those polyphenols were provided at the dose of 0 or 60 mg of active molecule in 100 ml of fermented milk (two bottles of 100 ml/day covering 25 and 20 % RDA for calcium and vitamin D, respectively). Consumption of the milk enriched in polyphenols significantly improved serum bALP activity (an osteoblastic marker), without significant modification of CTX, a marker for bone resorption. This favorable orientation of bone metabolism could be explained by the contribution of anthocyans, the only noticeable difference between the two test foods. This finding is independent of the initial calcium and vitamin D consumption. In conclusion, consumption of fermented milk enriched with calcium and ­vitamin D, containing blueberry, for 3 months, has corrected the insufficiency of vitamin D of postmenopausal women and resulted in improved bone formation, as indicated by the rise of a biomarker of osteoblastic activity. This benefit is probably related to the presence of blueberries (rich in polyphenols and phenolic acids).
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