Diet, Nutrition, and Bone Health

 Diet, Nutrition, and Bone Health

Abstract 

Osteoporosis is a debilitating disease that affects many older people. Fragility fractures are the hallmark of osteoporosis. Although nutrition is only 1 of many factors that influence bone mass and fragility fractures, there is an urgent need to develop and implement nutritional approaches and policies for the prevention and treatment of osteoporosis that could, with time, offer a foundation for population-based preventive strategies. However, to develop efficient and precocious strategies in the prevention of osteoporosis, it is important to determine which modifiable factors, especially nutritional factors, are able to improve bone health throughout life. There are potentially numerous nutrients and dietary components that can influence bone health, and these range from the macronutrients to micronutrients as well as bioactive food ingredients. The evidence-base to support the role of nutrients and food components in bone health ranges from very firm to scant, depending on the nutrient/component. This article initially overviews osteoporosis, including its definition, etiology, and incidence, and then provides some information on possible dietary strategies for optimizing bone health and preventing osteoporosis. The potential benefits of calcium, vitamin D, vitamin K1, phytoestrogens, and nondigestible oligosaccharides are briefly discussed, with particular emphasis on the evidence base for their benefits to bone. It also briefly considers some of the recent findings that highlight the importance of some dietary factors for bone health in childhood and adolescence. J. Nutr. 137: 2507S–2512S, 2007

Introduction 

Osteoporosis is a global health problem that will take on increasing significance as people live longer and the world’s population continues to increase in number (1). Thus, prevention of osteoporosis and its complications is an essential socioeconomic priority. There is an urgent need to develop and implement nutritional approaches (including functional foods) and policies for the prevention and treatment of osteoporosis. This article first briefly defines the principal disease of bone mass (i.e., osteoporosis) and considers its epidemiology and risk factors. It then focuses on the importance of certain dietary factors (in particular those that could be potential functional food ingredients for the prevention of osteoporosis) in bone health.

 Osteoporosis: definition and epidemiology 

Osteoporosis is defined as a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture (2). For the purposes of clinical diagnosis, a working party of the World Health Organization has redefined osteoporosis according to bone mass, at least for women. Their diagnostic criteria for osteoporosis, based on bone mineral content (BMC)3 or bone mineral density (BMD), include: normal, within 1 SD of the young adult reference mean for the population; osteopenia, between –1 and –2.5 SD of the young adult mean; osteoporosis more than –2.5 SD below the young adult mean; and established osteoporosis as the same mass definition but associated with a fragility fracture (3). Fragility fractures are the hallmark of osteoporosis and are particularly common in the spine, hip, and distal forearm, although they can occur throughout the skeleton. Osteoporotic fractures constitute a major public health problem. Currently, in the United States alone, 10 million individuals already have osteoporosis, and a further 34 million more have low bone mass, placing them at increased risk from this disorder (4). Moreover, 1 in 8 European Union (EU) citizens over the age of 50 y will fracture their spine this year (1). The estimated remaining lifetime risk of fractures in Caucasian women at age 50 y, based on incidence rates in North America, is 17.5%, 15.6%, and 16% for hip, spine, and forearm, respectively; the remaining lifetime risk for any fragility fracture approaches 40% in women and 13% in men (5). The incidence of vertebral and hip fractures increases exponentially with advancing age (6). This is of particular concern because it is projected that the number of elderly (80 y and older, in whom the incidence of osteoporotic fracture is greatest) in the EU population will grow from 8.9 million women and 4.5 million men in 1995, to 26.4 million women and 17.4 million men in 2050 (1). Similar demographic changes have been forecast for the U.S. population (7). Because of the increase in incidence rates of osteoporotic fractures with age, these demographic changes and increasing life expectancy will have a huge impact on the number of fractures that can be expected to occur. For example, the number of hip fractures occurring each year in the EU alone is estimated to rise from current figures of 414,000 to 972,000 by 2050, representing an increase of 135% (1). Hip fracture patients have an overall mortality of 15–30% (8), the majority of excess deaths occurring within the first 6 mo after the fracture. From an economic perspective, the expenses of hospital care and rehabilitation associated with osteoporotic fractures are a considerable fiscal drain for the health care system, exceeding those of other highly prevalent pathologies of the elderly, such as myocardial infarction (9). Osteoporosis costs national treasuries over V3500 million annually in hospital health care alone (1).

Risk factors for osteoporosis

 Low bone mineral mass is the main factor underlying osteoporotic fracture (10). Bone mass in later life depends on the peak bone mass achieved during growth and the rate of subsequent age-related bone loss. Development of maximal bone mass during growth and reduction of loss of bone later in life are the 2 main strategies of preventing osteoporosis (11). Consequently, any factor that influences the development of peak bone mass or the loss of bone in middle-age will affect later fracture risk. Several factors are thought to influence bone mass. These can be broadly grouped into factors that cannot be modified, such as gender, age, body (frame) size, genetics and ethnicity, and those factors that can be modified, such as hormonal status (especially sex and calciotropic hormone status), lifestyle factors including physical activity levels, smoking and alcohol consumption patterns, and diet (including functional foods). The interaction of these genetic, hormonal, environmental and nutritional factors influences both the development of bone to peak bone mass at maturity and its subsequent loss. The remainder of this article will focus on a selected number of dietary components/ nutrients that may influence bone health.

Diet, nutrition and bone health

 Many of the nutrients and food components we consume as part of a Westernized diet can potentially have a positive or negative impact on bone health (see Table 1). They may influence bone by various mechanisms, including alteration of bone structure, the rate of bone metabolism, the endocrine and/or paracrine system, and homeostasis of calcium and possibly of other bone-active mineral elements (12). These dietary factors range from inorganic minerals (e.g., calcium, magnesium, phosphorus, sodium, potassium, and various trace elements) and vitamins (vitamins A, D, E, K, C, and certain B vitamins), to macronutrients, such as protein and fatty acids. In addition, the relative proportions of these dietary factors derived from different types of diets (vegetarian vs. omnivorous) may also affect bone health and thus osteoporosis risk. Furthermore, in recent years a number of bioactive food components have been proposed as being beneficial for bone health. A review of all of these dietary factors is beyond the scope of the present article. Three important reports [the European Commission’s Report on Osteoporosis in the European Community: Action for Prevention (1); the U.S. Surgeon General’s Report on Bone Health and Osteoporosis (12); the World Health Organization’s report on Diet, Nutrition and the Prevention of Chronic

Diseases (13)] have stressed the importance of calcium and vitamin D in promoting bone health. Therefore, this section focuses on calcium and vitamin D but also briefly mentions selected nutrients/food components that also have important roles in bone health (such as vitamin K and dietary phytoestrogens). At present, however, the evidence base for these latter nutritional factors is less well developed (1,10,14).

Dietary calcium and its absorption. Calcium is required for normal growth and development of the skeleton (15). Adequate calcium intake is critical to achieving optimal peak bone mass and modifies the rate of bone loss associated with aging (16). Over the past decade, convincing evidence has emerged with respect to effects of dietary calcium on bone health in all age groups (1). The role of calcium in bone health has been extensively reviewed elsewhere (1,15–18). Unfortunately, there are a significant proportion of some population groups failing to achieve the recommended calcium intakes in a number of Western countries (18).

    Besides the amount of calcium in the diet, the absorption of dietary calcium in foods is also a critical factor in determining the availability of calcium for bone development and maintenance. There is therefore a need to identify food components and/or functional food ingredients that may positively influence calcium absorption to ensure that calcium bioavailability from foods can be optimized (18). This approach may be of particular value in individuals who fail to achieve the dietary recommended level of calcium and/or in those individuals with a low efficiency of intestinal absorption of calcium. Calcium in food occurs as salts or associated with other dietary constituents in the form of complexes of calcium ions (Ca21). Calcium must be released in a soluble, and probably ionized, form before it can be absorbed. Once in a soluble form, calcium is absorbed by 2 routes, transcellular and paracellular transport, and these have been reviewed elsewhere (19). In brief, the saturable transcellular pathway is a multistep process involving the entry of luminal Ca21 across the microvillar membrane into the enterocyte, then movement through the cytosol (i.e., translocation to the basolateral membrane), followed by active extrusion from the enterocyte into the lamina propria and, eventually, into the general circulation (see Fig. 1). The intracellular Ca21 diffusion is thought to be facilitated by a cytosolic calcium-binding protein, calbindin D9K, whose biosynthesis is dependent on vitamin D. Calbindin D9K facilitates the diffusion of Ca21 across the cell by acting as an intracellular calcium ferry or a chaperone. The active extrusion of Ca21 at the basolateral membrane takes place against an electrochemical gradient and is mainly mediated by Ca-ATPase. The entry of Ca21 across the apical membrane of the enterocyte is strongly favored electrochemically because the concentration of Ca21 within the cell (1027 to 1026 mol/L) is considerably lower than that in the intestinal lumen (1023 mol/L), and the cell is electronegative relative to the intestinal lumen. Therefore, the movement of Ca21 across the apical membrane does not require the expenditure of energy. It is widely believed that a Ca21 channel or integral membrane transporter [such as the transient receptor potential channel, subfamily V, member 6 (TRPV6), also known as calcium transporter (CaT1)] in the brush border membrane facilitates this entry into the enterocyte. Although each step in the transcellular movement of Ca21 has a vitamin D-dependent component, calbindin D9K is believed to be the rate-limiting molecule in vitamin D-induced transcellular calcium transport. The paracellular route of calcium absorption involves a passive calcium transport through the tight junctions between mucosal cells (see Fig. 1); it is nonsaturable, essentially independent of nutritional and physiological regulation, and is concentration dependent (19). Most calcium absorption in humans occurs in the small intestine, although there is some small colonic component (typically believed not to be .10% of total calcium absorption). However, the large intestine may represent a site of increased importance for calcium absorption when acidic fermentation takes place (19). This is important if one remembers that consumption of prebiotics will lead to acidic fermentation in the large intestine. When dietary calcium is abundant, the paracellular pathway is thought to be predominant. In contrast, when dietary calcium is limited, the active, vitamin D-dependent transcellular pathway plays a major role in calcium absorption.

    A number of food constituents have been suggested as potential enhancers of calcium absorption. Individual milk components, such as lactose, lactulose, and casein phosphopeptides have in the past attracted considerable attention, and these have been reviewed extensively elsewhere (20–22). In addition, there is a growing body of evidence to show that nondigestible oligosaccharides can improve calcium absorption in some lifestage groups. This evidence base has been reviewed elsewhere (19,23) and is the subject of 3 further articles in this Supplement (Abrams et al., Scholz-Ahrens and Schrezenmeir, V. Coxam).

Vitamin D.

 Vitamin D is found naturally in very few foods; endogenous synthesis of vitamin D, therefore, which occurs when skin is exposed to UVB radiation from sunlight during summer, is a principal determinant of vitamin D status. However, in latitudes above 40N and 40S (Rome, for example, is at latitude 42N), the dermal photoconversion of the precursor 7-dehydrocholesterol to vitamin D occurs little if at all during most of the 3–4 winter mo, with this period being extended to 6 mo in more northern latitudes (24). Thus, during the winter months there is an increased reliance on dietary supply of vitamin D. Of concern, vitamin D intakes are low in many populations (25), placing many people at risk of low vitamin D status, with possible consequences for bone health. Vitamin D deficiency is characterized by inadequate mineralization, or demineralization, of the skeleton. In children, severe vitamin D deficiency results in inadequate mineralization of the skeleton causing rickets, whereas in adults, it leads to a mineralization defect in the skeleton causing osteomalacia (15). In addition, the secondary hyperparathyroidism associated with low vitamin D status enhances mobilization of calcium from the skeleton (15). There is a considerable body of evidence that vitamin D deficiency is an important contributor to osteoporosis through less efficient intestinal absorption of calcium, increased bone loss, muscle weakness, and a weakened bone microstructure (26). Increasing vitamin D intake can significantly reduce risk of bone fracture in older people (26). In light of the high prevalence of low vitamin D status among large population groups in Europe, the United States, and elsewhere (15,16,27), strategies are needed to address this public.

health problem, including development of vitamin D-containing functional foods.

Vitamin K Recently, the identification of g-carboxyglutamyl (Gla)-containing proteins in bone, notably osteocalcin and matrix Gla protein, has generated much interest in the role of vitamin K in bone metabolism and bone health (28). The circulating concentration of under-g-carboxylate osteocalcin, a sensitive marker of vitamin K nutritional status (29), has been reported to be an indicator of hip fracture (30,31) and a predictor of BMD (15,32). Moreover, the findings of 2 large, prospective cohort studies [the Nurses’ Health Study (33) and the Framingham Heart Study (34)] support an association between relative risk of hip fracture and vitamin K intake. In the Nurses’ Health Study, vitamin K1 intakes of ,109 mg/d were associated with an increased risk of hip fracture in 72,327 women (33). In the Framingham Heart Study, elderly men and women in the highest quartile of vitamin K1 intake (median 254 mg/d) had significantly lower adjusted relative risk of hip fracture than did those in the lowest quartile of intake (median 56 mg/d) (34).

The above mentioned studies, however, were observational in nature, and this inevitably raises the issue of causal relationships and proof of causality. In terms of proof of causality, there is a general consensus that there is a need for well-designed, randomized vitamin K1 supplementation trials in adults to confirm observational findings and the role of vitamin K in bone metabolism and mass in healthy subjects (35). Clinical intervention studies presently being conducted or near completion in North America will help to elucidate this question and thus will substantiate whether vitamin K has the potential to be a functional food ingredient for bone health. Of interest, Braam et al. showed that relatively high-dose vitamin K1 supplementation (1 mg/d) for 3 y, if Coad ministered with calcium, magnesium, zinc, and vitamin D, reduced postmenopausal bone loss at the femoral neck (36). The dose of vitamin K used in this study, however, is unlikely to be achieved by dietary means and would require either supplementation or the functional food approach.

Dietary phytoestrogens Estrogen deficiency is a major contributory factor to the development of osteoporosis in women, and hormone replacement therapy (HRT) remains the mainstay for prevention of bone loss in postmenopausal women (37). Recently, as a consequence of poor uptake and adherence of HRT as well as potential concerns over an increased risk of malignancy and other side effects associated with the use of HRT, attention has been focused on the so-called dietary phytoestrogens as possible safe alternatives, or at least adjuncts, to HRT. Phytoestrogens are nonsteroidal compounds naturally occurring in foods of plant origin (especially soy-based foods) that structurally resemble natural estrogens and compete with them for binding estrogen receptors (38).

Currently, the data from human intervention studies are mixed in relation to potential beneficial effects of phytoestrogens on bone health (38). One of the most cited works in support of their potential beneficial effects for bone is that of Morabito et al. (39), who reported the findings of their randomized double-blind, placebo-controlled study in which the effects of purified genistein (a soy-based isoflavone) supplementation (56 mg/d) and continuous HRT for 12 mo on bone metabolism and BMD were evaluated and compared in early postmenopausal women. Genistein supplementation significantly increased BMD in the femur and lumbar spine, effects that appeared to be of similar magnitude to those achieved with HRT (39). The dose of genistein used in this study, however, far exceeds that naturally present in the normal Western diet (38) and could realistically be achieved only by supplementation or by the function food approach. A recent critical review of the health effects of soybean phytoestrogens in postmenopausal women concluded that there is a suggestion, but no conclusive evidence, that isoflavones from the sources studied so far have a beneficial effect on bone health (40). Further research is needed to clarify the role of dietary phytoestrogens in osteoporosis prevention.

Diet and bone health in childhood and adolescence

 About 90% of total adult bone mass is accrued by age 20, and a significant proportion of this is achieved during puberty alone (18). Thus, gaining an understanding of the role of dietary components in bone metabolism and bone mass in these early life stages is important because finding new strategies to maximize the accretion of bone during growth may help reduce the risk of osteoporosis in later life.

The importance of dietary calcium to bone health in childhood and adolescence has been emphasized (1,12,15). There is some concern about the proportion of adolescents, particularly girls, who appear to be failing to meet the dietary recommended level of calcium (18). Adolescence also appears to be the life stage during the first 2 decades of life that has the highest prevalence of low vitamin D status (41). It is well established that prolonged and severe vitamin D deficiency leads to rickets in children (15). Less severe vitamin D deficiency, although it does not cause rickets, may prevent children and adolescents from reaching their genetically programmed height and peak bone mass (27). For example, results from studies in adolescents provide evidence of a possible adverse effect of vitamin D deficiency and insufficiency for bone health in children (42–44). A recent 12-mo intervention study with supplemental vitamin D shows the benefits to BMC in adolescent Finnish girls (45). There is a need to consider various strategies for increasing vitamin D status of adolescents.

    Beyond the effect of calcium and vitamin D, there have been a number of recent studies that show the importance of other nutrients and food components. Kalkwarf et al. (46) investigated the relation between vitamin K intake (and status) and indices of bone health in children and adolescents (aged 3–16 y). Their findings suggest that better vitamin K status was associated with decreased bone turnover in healthy girls consuming a typical U.S. diet. However, vitamin K status was not consistently associated with BMC. O’Connor et al. (47) showed that better vitamin K status was associated with increased BMC in healthy peripubertal Danish girls, although no effects on bone metabolism were evident. Thus, there is a need for well-designed, randomized vitamin K1 supplementation trials in children and adolescents to confirm epidemiological findings of an association between vitamin K status and bone health.

As mentioned previously, there is a growing body of evidence to show that nondigestible oligosaccharides (especially inulin type fructans) can enhance calcium absorption. This is particularly the case in adolescents, and the studies illustrating this have been reviewed elsewhere (22,23). One recent study merits particular mention, namely that of Abrams et al. (48), who recently reported the findings of a 12-mo randomized, placebo controlled intervention trial with an inulin-type fructan (Synergy) in 9- to 13-y-old boys and girls. They found that calcium absorption was significantly higher in the inulin-type fructan supplemented group than in the placebo (maltodextrin) control group at 8 wk but also, interestingly, after 12 mo (48)

Furthermore, there was evidence that the additional calcium absorbed was retained within the body for use by skeletal tissue. The group receiving the inulin-type fructan had a greater increment in both BMC and BMD than did the control group (48). These findings strongly suggest that addition of selective nondigestible oligosaccharides to food represents an opportunity for increasing the uptake and utilization of calcium present in the diet.

It is also of interest that inulin-type fructans have been suggested to positively influence postmeal satiety and food intake (49), which might be of potential application in tacking childhood obesity, not only of importance for its own sake but also because childhood obesity has been shown to increase risk of childhood fracture (50).

The lack of effective treatments for degenerative diseases such as osteoporosis places increased emphasis on a preventative approach, including dietary strategies. In addition, it offers considerable opportunities for the development of functional foods. The development of nutritional policies as well as of functional foods for bone health must be based on a detailed understanding of the influence of dietary constituents on health. Particularly in the case of functional foods, their development must be supported by independent and appropriate scientific evidence to demonstrate efficacy with respect to claimed health benefits. Thus, more research on the role of diet on bone health is required. In addition, more emphasis should be placed on understanding the role of diet and nutrition on bone health during childhood and adolescence.