The Role of Diet in Osteoporosis Prevention and Management: Epidemiology and Pathophysiology (Ra Adler, Section Editor)

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Curr Osteoporos Rep

DOI 10.1007/s11914-012-0119-y

EPIDEMIOLOGY AND PATHOPHYSIOLOGY (RA ADLER, SECTION EDITOR)

The Role of Diet in Osteoporosis Prevention


and Management
Silvina Levis & Violet S. Lagari

# Springer Science+Business Media, LLC (outside the USA) 2012

Abstract Diet, a modifiable osteoporosis risk factor, plays skeletal health. Nutrition and physical activity have a strong
an important role in the acquisition and maintenance of bone influence on the acquisition and maintenance of bone mass.
mass. The influence of diet on bone begins in childhood; During childhood, adequate dietary intake can help an indi-
even maternal diet can influence bone mass in the offspring. vidual increase bone mass and reach peak bone mass; in
A good general nutritional status and adequate dietary pro- adults, proper nutrition can slow down bone remodeling. It
tein, calcium, vitamin D, fruits, and vegetables have a pos- is increasingly recognized that in addition to adequate intake
itive influence on bone health, while a high caloric diet and of calcium and vitamin D other nutrients might play an
heavy alcohol consumption have been associated with lower important role in bone health [1]. General nutritional status
bone mass and higher rates of fracture. The evidence for a and dietary protein, fat, fruits, vegetables, and alcoholic
role of other minerals and vitamins in skeletal health is not beverages play a key role in skeletal growth and mainte-
as strong, but recent evidence suggests that vitamins C and nance of bone mass. Diet is a modifiable risk factor for
K might also have an effect on bone. osteoporosis and an easy target for osteoporosis prevention
and treatment programs. However, it is difficult to isolate
Keywords Diet . Nutrition . Osteoporosis . Fractures . and study each dietary component. Instead, many have
Bone health examined different food groups, types of diet, or nutritional
status. This update on the effect of diet on skeletal health
mostly includes original articles published between January
Introduction 2011 and June 2012. This review reports findings of epide-
miologic, observational, and intervention studies of the ef-
Although heritability explains a significant part of an indi- fect of diet on bone health in humans, but does not include
vidual’s bone mass, other factors can also profoundly affect animal or in vitro studies, or studies of dietary supplements.

S. Levis (*)
Geriatrics Institute and Department of Medicine, Calcium
University of Miami Miller School of Medicine,
P.O. Box 016960 (D-503), Miami, FL 33101, USA
e-mail: slevis@med.miami.edu More than 99 % of the body’s calcium is in the bones and
teeth. Insufficient calcium intake results in secondary hy-
S. Levis perparathyroidism, which in turn increases bone turnover
Geriatric Research, Education, and Clinical Center,
Bruce W. Carter Veterans Affairs Medical Center,
and accelerates bone loss. Although there is general agree-
Miami, FL 33125, USA ment regarding the importance of having an adequate calci-
um intake for bone health, there is no consensus on the
S. Levis : V. S. Lagari appropriate daily dose, as reflected by the wide range of
Endocrinology Section,
Bruce W. Carter Veterans Affairs Medical Center,
calcium intake recommendations from different organiza-
Miami, FL 33126, USA tions, ranging from 700 mg in the UK to 1300 mg in
e-mail: vlagarilibhaber@med.miami.edu Australia and New Zealand [2–4]. Recognizing the role of
calcium in skeletal health, the Institute of Medicine in the
S. Levis : V. S. Lagari
Department of Medicine,
United States has made specific recommendations on calci-
University of Miami Miller School of Medicine, um intake requirements listed in the Table 1 [5••]. The
Miami, FL 33125, USA recommended dietary allowance, or RDA, was based on
Curr Osteoporos Rep

Table 1 Institute of Medicine 2011 Dietary Allowance (RDA) and fracture were associated with low bone mineral density
Tolerable upper Limit (TUL) recommendations for calcium
(BMD). In this population, diet did not influence risk in spite
Age RDA (mg/day) TUL (mg/day) of 55 % of participants having low calcium intake [8]. It is
important to note that assessments of calcium intake are prone
19–50 1000 2500 to inaccuracies; food frequency questionnaires might overes-
51–70 (men) 1000 2000 timate calcium intake and underestimate total energy intake
51–70 (women) 1200 2000 [9, 10]. Assessments based on 24-hour recall might include or
71 and older 1200 2000 omit foods that are eaten on other days, or report food com-
Pregnant or lactating women 1000 2500 position, and portion size incorrectly [11]. Furthermore, in the
design of calcium supplementation clinical trials, habitual
Recommended Dietary Allowance (RDA) covers the requirement of
≥97.2 % of the population; Tolerable upper Limit (TUL) is not a target dietary calcium intake is not always accounted despite its
intake but the level above which there is a risk of adverse effects potential influence on the outcome of the study.
Clinicians frequently prescribe calcium supplements, but
often patients prefer to increase their calcium intake through
accepted skeletal health endpoints, which included optimal diet [12]. Two French studies have evaluated the effects of 2
calcium absorption, bone density, osteoporotic fractures, daily servings of calcium- and vitamin D-fortified soft cheese
and osteomalacia. providing a daily dose of 400 mg of calcium, 2.5 mcg (100 IU)
It has been consistently shown that the US population does of vitamin D3, and 13.8 g of protein vs usual diet [13, 14]. One
not meet the current RDA recommendations. National Health of the studies was conducted in older institutionalized women
and Nutrition Examination Survey (NHANES) is a survey of a mean age 87±6 years with hypovitaminosis D and calcium
representative group of the US civilian, non-institutionalized intake below 700 mg/day. After 6 weeks, there were signifi-
population. Assessment of both dietary and supplemental cant increases in 25-hydroxyvitamin D levels, higher levels of
calcium intake in the US population in NHANES 2003– serum insulin-like growth factor-I (IGF-I), a bone anabolic
2006, suggests that calcium intake declines in older American factor, and significant reductions in 2 markers of osteoclast
adults, partly due to a concomitant decline in energy intake activity and bone resorption, bone specific acid phosphatase
[6]. Both men and women age 50 and older have a median tartrate resistant acid phosphatase isoform 5b (TRAP 5b), and
intake considerably below the RDA. Median dietary calcium serum carboxy-terminal cross-linked telopeptide of type I
intake in men declined by 22 % from the youngest to the bone collagen (CTX) [13]. The same intervention was tested
oldest group, from 942 mg daily to 728 mg daily. In women, in younger women, mean age 56±3.9 years, who were, on
calcium intake declined 14 % from the youngest to the oldest, average, within 7.5 years from menopause and had calcium
from 628 mg daily to 589 mg daily. The survey reported that intake below 650 mg/day [14]. After 6 weeks, there was no
about 50 % of adults take calcium supplements and that, with difference between the intervention and the control groups in
age, the level of dietary calcium decreased while the frequen- CTX. However, women in the intervention group had lower
cy of use of supplements increased. However, the increase in levels of TRAP 5b and higher levels of IGF-I. These findings
calcium supplement use did not suffice to counteract the suggest that in this population of menopausal women with
decrease in dietary consumption. Women not using calcium baseline low calcium intake and hypovitaminosis D, bone
supplements also had lower dietary calcium intake, which resorption, and the risk of fractures could be reduced with
remained constant throughout the lifespan. In contrast, sup- the long-term consumption of 2 portions of soft plain cheese
plement users had a steady decrease in dietary calcium, most that supply additional protein, calcium, and vitamin D.
evident in older women, suggesting an age-related greater
reliance on supplements.
Time and again, epidemiologic and prospective studies Vitamin D
have supported the role of adequate calcium intake in the
prevention of osteoporosis and fractures, particularly in pop- Severe vitamin D deficiency (25-hydroxyivitamin D <10 ng/
ulations who are deficient. A prospective, longitudinal study mL) is associated with rickets and osteomalacia. Recent evi-
based on the Swedish Mammogram Cohort that followed over dence suggests that gastrointestinal calcium absorption and
61,000 women and assessed their diet by repeated food fre- bone mineralization are inadequate in vitamin D insufficiency,
quency questionnaires, determined that daily dietary calcium which some define as 25-hydroxyivitamin D levels <20 ng/
intake below 700 mg was associated with increased risk of mL and others as <30 ng/mL. In addition to supporting
fracture and that the highest reported calcium intake did not skeletal health, improving vitamin D status in elderly individ-
further reduce fracture risk [7•]. A study conducted in south- uals reduces the risk of falling, thus, having a dual effect in the
eastern Brazil showed that known osteoporosis risk factors prevention of fractures. Few foods naturally contain vitamin
such as age, time since menopause, and maternal history of D. Therefore, in most adults residing in urban areas or in
Curr Osteoporos Rep

northern latitudes, adequate levels depend on sun exposure or The Canadian Multicentre Osteoporosis Study, a population-
vitamin supplements. In some countries, the most common based cohort, evaluated the association between dietary patterns
dietary sources of vitamin D are vitamin D-fortified milk or and fracture in postmenopausal women and men age 50 years
milk substitutes, other dairy products, and cereals. The dose of and older [18•]. The study found that increased intake of
vitamin D in these fortified foods is usually small and may not nutrient-dense foods was associated with a lower fracture risk,
be sufficient to maintain normal serum levels in all individ- independent of other important risk factors. The magnitude of
uals, particularly in those at higher risk of vitamin D insuffi- the association was comparable to the association between
c i e n c y o r d e f i c i e n c y, s u c h a s p e r s o n s w h o a r e tobacco smoking and fracture. The authors propose that the
institutionalized, obese, older, or have darker skin. population fracture burden could be reduced by encouraging
the consumption of fruits, vegetables and whole grains, in
addition to other public health measures. In a study of dietary
patterns and bone density among over 3000 Scottish women, a
Minerals
healthy diet that included high intake of fruits and vegetables
was associated with decreased bone resorption, while a diet rich
Although it is generally agreed that adequate protein, calcium,
in processed foods was linked to decreased bone density [19].
and vitamin D are the most important nutrients for bone
A systematic review of studies in women 45 years of age
growth and skeletal health, several studies suggest that other
and older had opposite findings. It concluded that there is
minerals might also play a role in bone metabolism, and thus
little evidence to support any significant role of dietary fruit
osteoporosis risk. A 2-year supplementation study with 2 mg
and vegetable intake on markers of bone turnover, bone
of copper and 12 mg of zinc daily in postmenopausal women
mineral density, and fractures [20]. However, the authors
receiving adequate calcium and vitamin D supplementation,
acknowledge that there was considerable risk of bias and
reported that zinc supplementation might be beneficial to bone
heterogeneity between the studies.
health in those with usual intakes of less than 8 mg daily, but
not in those consuming adequate amounts [15].
Protein

Fruits and Vegetables Epidemiologic studies have shown a positive association


between protein intake and bone health, including increased
Dietary fruits and vegetables have the potential to affect bone density and reduced fracture risk [21]. Results of a
bone health. Fruits and vegetables contain (1) minerals such recent prospective cohort study in more than 2000 Chinese
as potassium, magnesium, and calcium; (2) antioxidants men and women age 65 and older that assessed food intake
such as polyphenols; (3) phytoestrogens; and (4) vitamin by a food frequency questionnaire and examined changes in
C and vitamin K, both necessary for the synthesis of the bone density over 10 years, suggested that in older men,
bone matrix. In addition, diets rich in fruits and vegetables higher fish intake was associated with smaller bone loss in
result in lower dietary acid load due to their high content of the hip, while lower protein intake was associated with
potassium and magnesium. (An acid environment is known greater hip bone loss [22]. However, some claim that
to stimulate osteoclasts and reduce osteoblast activity.) the acidifying properties of diets high in protein ad-
Reactive species are produced as a result of normal versely affect bone metabolism and result in increased
cellular processes and play an important role in cell signal- calcium urinary excretion and bone loss, as described in
ing and gene transcription. Reactive species include free the section below [23].
radicals, reactive oxygen species, and reactive nitrogen spe-
cies. Oxidative stress develops when there is an imbalance
between the production of reactive species and the ability of Type of Diet
the body to control them using antioxidants. Oxidative
stress contributes to the development of many chronic dis- It is not clear if individual dietary components or the type of
eases, including osteoporosis [16]. Exogenous antioxidants diet have the greatest influence on bone metabolism.
in the diet play an important role in reducing oxidative stress
[17]. Exogenous antioxidants are rich in vitamin C, the Western Diet
primary antioxidant, vitamin E, and carotenoids and can be
found in most fruits, vegetables, nuts, and seeds. It has been Cross-sectional data from NHANES 1999–2000 and 2001–
suggested that bone anabolic action derived from the diet is 2002 was used to evaluate the influence of healthy eating and
through the targeting of bone morphogenetic protein signal- markers of bone turnover in postmenopausal women age
ing pathways. 45 years and older [10]. The study found a negative
Curr Osteoporos Rep

association between milk intake and urinary NTX, a marker of to an average of one half cup per day [28]. Dark green
bone resorption; women in the lowest tertile of milk intake vegetables are also a source of dietary calcium. Although
had the highest NTX. There was no dose–response, suggest- their calcium content and bioavailability is much lower, if
ing that there is no further improvement in bone metabolism consumed in large quantities, dark green vegetables might
once a sufficient intake is achieved. However, the high fre- provide an adequate daily calcium dose in people who do
quency of zero values in subcategories of foods usually in- not drink milk. In Asian populations, vegetables might be
cluded in a healthy diet, such as fish, dark-green vegetables, an important source of calcium, as shown by a prospective
citrus fruits, and milk, cheese and yogurt, could have limited study in Korean women between the ages of 50 and 70,
the effect of these foods on skeletal health. In addition, those which reported that after adjusting for potential confound-
in the highest tertile of energy-adjusted (mg sugar/kcal) added ers the intake of plant-derived calcium was associated with
sugar intake had the highest levels of bone alkaline phospha- higher bone density [29]. The average vegetable intake in
tase, a marker of osteoblastic activity, supporting previous the cases was 6 to 8 servings per day.
evidence that high candy consumption, which usually indi-
cates a nutrient-poor diet, is associated with low BMD in older Acid vs Alkaline Diet
women [24]. In the UK twin study, the traditional 20th
century English diet consisting of mostly fried fish, fried Although recent evidence has demonstrated that sufficient
potatoes, legumes, red meats, savory pies, and cruciferous protein intake is necessary to maintain bone integrity, it has
vegetables, was associated with lower bone density [25•]. been suggested that diets high in animal protein should be
As in the NHANES study, the UK twin study was unable considered a risk factor for osteoporosis and fractures [30].
to show that a diet high in fruit and vegetables was The “acid ash hypothesis” claims that acid-generating diets,
associated with higher bone density, as previously shown such as those rich in protein, dairy products, and grains
in the Framingham cohort, partly because the average cause the release of bicarbonate from the bone to neutralize
intake of fruits and vegetables in the UK twin study was the acid and prevent systemic acidosis [23]. The hypothesis
low. The Framingham Heart Study is a longitudinal cohort proposes that the resulting resorption of bone mineral and
started in 1948 to examine risk factors for heart disease. A increased urinary calcium excretion produces overall rapid
substudy of the Framingham cohort conducted in elderly loss of skeletal calcium and bone mass. Alkaline or “acid
adults found that in men, a diet high in fruit, vegetables ash” diets, supplements and salts are being marketed with
and cereal was associated with higher bone density [24]. the claim of counteracting the allegedly adverse skeletal
In women, results were not as clear, but those consuming effect of an acid diet [31].
more fruits, vegetables, and cereal tended to have higher In order to clarify the role of protein in bone metabolism,
bone density. Both men and women consuming the most postmenopausal women were given a low-protein diet with
candy had significantly lower bone density than other low-potential renal acid load vs a high-protein diet with
groups. high-potential renal acid load over 1 week [32•]. The high
meat protein diet increased the fractional absorption of
Vegetarian Diet dietary calcium, which almost compensated for the in-
creased urinary calcium excretion caused by the high renal
It has been proposed that, as a result of the absence of acid load. The high meat diet did not change markers of
animal and dairy products in their diet, vegans and vegeta- bone resorption or formation but increased IGF-1 and de-
rians have lower bone mass due to a lifelong low intake of creased parathyroid hormone levels, suggesting a beneficial
protein and calcium. The effect of a vegetarian diet on bone effect on bone health [32•]. A meta-analysis and systematic
loss was examined in 210 postmenopausal women, half of review restricted to trials of high-quality randomized, and
whom were omnivores and half vegans. After 2 years, bone prospective observational trials at low risk of bias, conclud-
loss was comparable in the 2 groups, although vegans had ed that there is no evidence to support the hypothesis that
higher prevalence of vitamin D insufficiency [26]. acid from a modern diet results in osteoporosis, or that an
alkaline load from either diet or supplements prevents the
Asian Diet disease [33]. Although the data shows a positive association
between acid load from diet and urinary calcium excretion,
In Western diets, dairy products are the main source of there is no support for any causal relationship with whole
calcium, potassium, magnesium, and protein. Milk con- body calcium balance, markers of bone resorption, or
sumption in Asian diets is usually low [27]. The Korean changes in bone density, or fractures. The review also con-
National Health and Nutrition Examination Survey cluded that consuming foods or alkaline supplements to
reported a daily calcium intake of about 500 mg among offset dietary acid is unlikely to result in improved bone
adults aged 50 to 65 years, with milk consumption limited health.
Curr Osteoporos Rep

Caloric Intake increased bone loss and risk of fractures [39]. The mecha-
nism is multifactorial, with uncoupling of bone remodeling
Obesity increases the risk for chronic illnesses, such as and increased bone loss. Chronic heavy consumption causes
diabetes and cardiovascular disease. In the US, adults age inhibition of osteoblast proliferation, reductions in osteo-
60 and over are more likely to be obese than young adults; blast number and activity, and increased osteocyte apopto-
over 42 % of adult women are obese [34]. Although it has sis, resulting in decreased bone formation. Also, bone
been assumed that obesity protects against bone loss be- resorption markers are increased with heavy alcohol con-
cause of increased mechanical loading, a recent study in sumption, which also induces oxidative stress, resulting in
premenopausal obese women determined that visceral ab- increased signaling of receptor activator of nuclear factor-
dominal adipose tissue has a detrimental effect on bone κB ligand-receptor activator of nuclear factor-κB (RANKL-
mineral density [35]. Low-calorie diets are often recommen- RANK), and enhanced osteoclastogenesis. In addition, ex-
ded to combat obesity, and some have raised the concern cessive alcohol intake increases oxidative stress and bone
that the chronic consumption of a diet low in calories, marrow fat accumulation. Furthermore, lower testosterone
proteins, and minerals could adversely affect bone health. and estrogen levels have been reported in alcoholic men and
In fact, studies of overweight or obese postmenopausal women, respectively. Lastly, the poor nutritional status,
women on low-calorie diets have demonstrated that there decreased caloric intake, smoking, sedentary lifestyle, and
is bone loss associated to weight loss. A recent study exam- liver disease that might be associated with alcoholism could
ined the role of caloric restriction on bone health in older worsen the deleterious effects of alcohol on bone, which
women of normal weight [36]. Bone density was maintained appear to be dependent on the dose and duration.
in those with 80 % to 100 % caloric intake of the recom- A study of over 2000 postmenopausal twins enlisted in a
mended daily requirement (RMDR). Those having an ex- UK register evaluated the association of diet and alcohol
tremely low daily caloric intake of about 55 % of the RMDR intake to bone density [25•]. This UK twin study avoided
had lower femoral BMD and a trend towards lower bone the usual confounding effects of age and genotype and
density in the spine, raising concerns for non-obese older found a positive association between alcohol intake from
women who might limit their caloric intake to maintain a wine only and spinal bone density. In a study of nonagenar-
slim body habitus. ian and centenarian Chinese women, current and former
alcohol consumption more than doubled the risk of osteo-
porotic fracture [42]. The Fujiwara-kyo Osteoporosis Risk
Influence of Prenatal Diet in Men Study, conducted in over 2000 Japanese men found
that after adjusting for several confounders, alcohol intake
Prenatal nutrition can have a considerable influence on was positively correlated with bone density, up to a daily
postnatal health. Prenatal nutrition depends on the maternal intake of 55 g [43]. In those men consuming ≥55 g per day,
diet during the gestation period. Both maternal caloric ex- alcohol intake was inversely correlated with bone density.
cess as well as caloric restriction can affect skeletal acqui-
sition in the offspring [37].
Non-alcoholic Beverages

Alcohol The consumption of soft drinks, because of their caffeine


and high phosphoric acid content, has been considered a risk
Alcoholism is a major cause of secondary osteoporosis. factor for osteoporosis, although it is also believed that the
Although mild to moderate alcohol intake has been associ- adverse effect is mainly due to the displacement of healthier
ated with high bone density, high alcohol consumption is beverages. In the Framingham Osteoporosis Study, cola
associated with osteoporosis and falls. Though the mecha- beverage intake was associated with lower BMD in the hip
nism by which mild to moderate alcohol consumption [44]. A recent study in postmenopausal American-Indian
results in improved bone health is unknown, it might be women of the Northern Plains and American Southwest
explained by decreased bone remodeling, as evidenced by with osteoporosis did not find any association between soda
lower levels of osteocalcin, CTX, and C-telopeptide of type consumption and osteoporosis risk [45]. However, analyses
I bone collagen (NTX) after light alcohol intake [38]. One confirmed confounding between soda consumption and age
daily drink for women and 2 for men is considered safe for and BMI, suggesting that any potential effects of soda
bone health [39, 40]. A recent meta-analysis reported lower consumption on bone health are largely mediated through
risk of fractures in persons consuming 0.5 to 0.1 alcoholic these factors. Green tea contains naturally occurring poly-
drinks per day, compared with abstainers [41]. On the other phenols, which are known to have anti-oxidative properties.
hand, heavy alcohol consumption is associated with Although no clinical trials have been published, in vitro
Curr Osteoporos Rep

studies suggest that green tea might have beneficial effects Press; 2011. Calcium and vitamin D intake recommendations for
the US population.
on osteoblasts [46, 47]. In South America, Yerba Mate tea
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