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NUTRITION, EXERCISE, AND LIFESTYLE IN OSTEOPOROSIS (CM WEAVER AND R DALY, SECTION EDITORS)
Dietary Approaches for Bone Health: Lessons
from the Framingham Osteoporosis Study
&Kelsey M. Mangano
&Robert R. McLean
&Marian T. Hannan
Douglas P. Kiel
#Springer Science+Business Media New York 2015
Abstract Osteoporosis is characterized by systemic impair-
ment of bone mass, strength, and microarchitecture, resulting
in increased risk for fragility fracture, disability, loss of inde-
pendence, and even death. Adequate nutrition is important in
achieving and maintaining optimal bone mass, as well as
preventing this debilitating disease. It is widely accepted that
adequate calcium and vitamin D intake are necessary for good
bone health; however, nutritional benefits to bone go beyond
these two nutrients. This review article will provide updated
information on all nutrients and foods now understood to alter
bone health. Specifically, this paper will focus on related re-
search from the Framingham Osteoporosis Study, an ancillary
study of the Framingham Heart Study, with data on more than
5000 adult men and women.
Keywords Nutrition .Diet .Bone mineral density .Fracture
Osteoporosis is a major public health problem for adults
worldwide. Osteoporosis is responsible for two million bro-
ken bones and $19 billion in related costs every year .
Historically, calcium and vitamin D are the primary nutrients
considered for osteoporosis prevention in older adults. Other
recommended prevention approaches include engaging in reg-
ular exercise, avoiding smoking and limiting alcohol intake.
In the last two decades, several advancements have been
made, which warrant reconsideration of existing dietary strat-
egies for osteoporosis prevention. To date, numerous studies
have related additional nutrients with bone health, such as
vitamins A, B, C, E, K; minerals (potassium, magnesium,
silicon); and macronutrients (protein and fats). Studies have
also gone beyond single nutrient associations and linked
foods, food groups, and dietary patterns with bone health. It
is important to synthesize this body of work to determine
which dietary approaches can be maximized for optimal bone
health and osteoporosis prevention. In this paper, we review
research studies on the relation between bone health with nu-
trients, foods, and dietary patterns originating from the
Framingham Osteoporosis Study.
The Framingham Osteoporosis Study is an ancillary study
of the Framingham Heart Study, a population-based cohort
that began in 1948 to examine risk factors for heart disease.
This review will focus on studies from the Framingham
Original Cohort, which includes older men and women
(5209 men and women enrolled, mean age 77 years, range
68–96), and the Framingham Offspring Cohort, which in-
cludes adult children of the Framingham Original Cohort
and their spouses (5124 men and women, mean age 55 years,
range 26–86). In both cohorts, diet was measured using the
Willett food frequency questionnaire [2,3] at baseline, and
bone health was assessed across several bone mineral density
This article is part of the Topical Collection on Nutrition, Exercise, and
Lifestyle in Osteoporosis
Kelsey M. Mangano
Robert R. McLean
Marian T. Hannan
Douglas P. Kiel
Institute for Aging Research, Hebrew SeniorLife, Department of
Medicine, Beth Israel Deaconess Medical Center, Harvard Medical
School, 1200 Centre St., Boston, MA 02131, USA
Curr Osteoporos Rep
(BMD) measurements and hip fractures were confirmed
Fruit and Vegetable Intake
Fruits and vegetables provide a multitude of micronutrients
such as vitamin K, folate, magnesium, potassium as well as
antioxidants such as vitamin C and carotenoids. Higher fruit
and vegetable intakes have been associated with higher BMD
 and less BMD loss over time . A systematic review of
eight studies concluded that in post-menopausal women,
cross-sectional studies support the positive relation between
fruit and vegetable intake with bone health. However, the
evidence of a beneficial effect of fruits and vegetables in os-
teoporosis prevention in prospective cohorts and randomized
controlled trials is less clear . A recent study in middle-aged
and older men and women linked fruit and vegetable intake
less than the recommended five servings/day with higher risk
of hip fracture [7•]. In the Framingham Original cohort, fruit
and vegetable intake was positively associated with BMD in
both men and women (in a cross-sectional analysis) and with
less BMD loss at the hip in men alone . Furthermore, die-
tary patterns rich in fruits and vegetables were linked with
higher BMD in men . This review summarizes reports on
selected nutrients within fruits and vegetables and the evi-
dence for their role in bone health.
Several studies have implicated oxidative stress in the patho-
genesis of osteoporosis [10–12]. Antioxidants such as vitamin
C suppress osteoclast activity through their antioxidant action.
Additionally, vitamin C acts as a cofactor in promoting oste-
oblast differentiation  and acts as a cofactor for collagen
formation and synthesis of hydroxyproline and hydroxylysine
required for the formation of stable triple helixes . In line
with this thought, several epidemiologic studies have exam-
ined the association of vitamin C in relation to BMD [15–19]
and fractures [20,21]. Results from these studies indicate a
complex association involving interaction of vitamin C with
nutritional factors [vitamin E and calcium intake  and non-
nutritional factors [smoking , estrogen use/hormonal ther-
apy after menopause].
In the Framingham Original cohort, among men, higher
dietary vitamin C intake was associated with less femoral neck
BMD loss [0.021 g/cm
less bone loss in the highest tertile of
dietary vitamin C (median intake of 209 mg/day) vs. lowest
tertile of dietary vitamin C (median intake of 86 mg/day)]. No
significant associations were observed among women. In sub-
group analyses, negative cross-sectional associations were ob-
served between total and supplemental vitamin C intake and
trochanter BMD among current male smokers . In
contrast, among male non-smokers, total vitamin C intake
was positively associated with femoral neck BMD. In the
same cohort, participants in the highest tertile of total vitamin
C intake (diet+supplements; median=313 mg/day) had 44 %
lower hip fracture risk over 15 years compared to those in the
lowest tertile (median= 94 mg/day) . Participants in the
highest category of supplemental vitamin C intake (median=
260 mg/day) had 69 % lower hip fractures risk compared to
non-supplement users. The level of vitamin C intake for pro-
tection against hip fracture in this study and for BMD in a
previous study  was much higher than that of the USA
recommended dietary allowance of 90 mg/day for men and
75 mg/day for women. Interestingly, in a recent double-blind,
controlled clinical trial of 90 older adults over a 12-month
period, administration of 1000 mg of ascorbic acid together
with 400 IU of alpha-tocopherol was shown to be useful in
decreasing hip BMD loss significantly, compared to no treat-
ment (12 month within group difference in hip BMD was
(in treatment group) vs. −0.0056 g/cm
group), Ptreatment vs. Placebo= 0.047) . Further research
is needed to ascertain optimal intakes of vitamin C for osteo-
porosis and fracture prevention with particular attention to its
interaction with smoking and alpha-tocopherol intakes.
Data from several in vitro [25–27] and in vivo [28–30]studies
suggest that further investigation into the relationship between
carotenoids and bone health is warranted due to their antiox-
idant properties. In particular, an inverse relation of carotenoid
and lycopene with biochemical markers of bone turnover has
recently been shown in post-menopausal women .
However, few longitudinal studies have examined the associ-
ation between carotenoids other than β-carotene  with
bone loss or fracture risk. In the Framingham Original cohort,
associations between intake of total carotenoids and individu-
al carotenoids were evaluated with bone loss at the hip, spine,
and radial shaft over 4 years of follow-up. In women, lyco-
pene intake was protective against lumbar spine BMD loss
over 4 years. In men, intakes of total carotenoids, β-carotene,
lycopene, and lutein+zeaxanthin were protective against tro-
chanter bone loss . Further, participants in the highest
tertile of total carotenoid intake had 46 % lower hip fracture
risk and participants with higher lycopene intake had 34 %
lower risk of hip fracture and 34 % lower risk of non-vertebral
fracture . No significant associations were observed with
other carotenoids. Data from other cohorts support the link
between individual carotenoids and reduction of hip fracture
risk . Specific to lycopene, restriction studies of lycopene
have shown significant increases in oxidative stress parame-
ters and the bone resorption marker N-telopeptide of type I
collagen in post-menopausal women, which were reversed
with lycopene supplementation [35,36]. Taken together, these
Curr Osteoporos Rep
results suggest a protective role of several carotenoids for
BMD and fracture risk in older adults with most consistent
results for lycopene intake.
Folate and B12
In the USA, refined grain products, including enriched breads,
cereals, and flour, along with fruits and vegetables, have be-
come a primary source of folate since the 1998 FDA mandate
on folic acid fortification. There is little evidence that folate
has any direct involvement with bone biology; however, it
may indirectly influence bone quality and fracture risk
through its role in homocysteine metabolism. Data from the
Framingham Original cohort were among the first to identify
elevated plasma homocysteine concentration as a strong risk
factor for hip fracture . Although the biologic mechanism
linking homocysteine to bone health remains unclear,
McLean’s initial findings published in 2004 stimulated a surge
in research investigating the relations of folate and vitamin
B12 with bone health because low status of these vitamins is
a primary determinant of elevated homocysteine in older
adults. Unlike folate, vitamin B12 is not present in plant foods
but is found primarily in animal products and fortified break-
fast cereals. Because modification of dietary intakes of folate
and vitamin B12 can effectively lower blood homocysteine
concentrations, these nutrients were hypothesized as potential
dietary interventions for improving bone health.
Our work in the Framingham Study suggests that vitamin
B12, though perhaps not folate, may be an important determi-
nant of bone health. In the Framingham Offspring cohort,
participants with plasma vitamin B12 concentrations <148
pM (250 pg/ml; a commonly used cut-off for vitamin B12
deficiency) had significantly lower BMD than those with
B12 above the cut-off . In the Framingham Original co-
hort, neither plasma folate nor plasma vitamin B12 concentra-
tions were associated with BMD loss over time . Further,
plasma folate was not associated with risk of hip fracture,
though participants with plasma vitamin B12 concentrations
in the deficient range (<148 pM) had increased risk for hip
fracture compared to those with Bnormal^plasma vitamin
B12 (≥258 pM). This association was attenuated after adjust-
ment for baseline BMD, suggesting that the effect of vitamin
B12 on fracture risk may be through its influence on BMD.
A meta-analysis of 27 observational studies investigating
the relation of folate and vitamin B12 with bone health sug-
gested a 4 % reduction in fracture risk per 50 pM increase in
vitamin B12 concentration (RR= 0.96, 95 % CI= 0.92, 1.00)
. For folate and fracture risk, there were not enough stud-
ies to allow a robust conclusion. Thus, the evidence from
Framingham and other studies suggests that folate may not
be important for bone health, while low vitamin B12 status
may be a modest risk factor for fracture. Supplementation with
vitamin B12 and folic acid has shown mixed results [41–44].
Thus, little evidence supports folate or vitamin B12 supple-
mentation as a means to prevent fracture.
In Western diets, the major form of dietary vitamin K is
phylloquinone (vitamin K1). Vitamin K is a necessary factor
for the carboxylation of osteocalcin, a bone-specific protein
produced by osteoblasts that is among the most abundant bone
matrix proteins and also plays a role in bone mineralization
. Insufficient vitamin K may lead to undercarboxylation of
osteocalcin and consequently contribute to age-related bone
loss and fractures.
In the Framingham Original cohort, those with dietary
phylloquinone intake in the highest quartile (median 254 μg/
day) had 65 % lower hip fracture risk than those in the lowest
quartile (median 56 μg/day), yet intake was not associated
with either BMD at baseline or BMD loss at any of the sites
examined (hip, spine, wrist) . In the younger Offspring
cohort, phylloquinone intake was similarly not associated
with BMD in men, but women in the lowest intake quartile
(mean 70.2 μg/day) had significantly lower mean hip (but not
spine BMD) than women in the highest quartile (mean
309 μg/day) . In contrast to dietary intakes, lower plasma
phylloquinone and higher percent serum undercarboxylated
osteocalcin (%ucOC) were significantly associated with lower
BMD at the hip, but not the spine. Among women, lower
plasma phylloquinone was associated with lower spine
BMD only in post-menopausal women using estrogen .
In the same cohort, plasma phylloquinone, but not %ucOC
was positively associated with heel ultrasound measures in
men only, while there was no association with dietary
phylloquinone intake . Our Framingham results reflect
the totality of the evidence from observational studies, which
has been previously reviewed [50,51] and provides moderate
to weak evidence supporting low vitamin K status as a risk
factor for poor bone health.
Several randomized trials have assessed the effect of vita-
min K supplementation (particularly menaquinone, vitamin
K2) on BMD and fractures, the results of which have been
summarized in recent systematic reviews and meta-analyses
[52–55]. The evidence suggests that vitamin K supplementa-
tion reduces the rate of bone loss, though the effect is very
modest. Menaquinone supplementation may reduce fracture
risk, though there is not enough evidence to draw definitive
conclusions regarding the effect of phylloquinones.
Potassium, Magnesium, and Alkaline Diets
Research suggests that an alkaline diet may prevent bone loss
and fracture. Potassium and magnesium are two dietary con-
stituents found in fruits and vegetables that contribute to a
higher alkaline state within the body. In the Framingham
Curr Osteoporos Rep
Original cohort, cross-sectional analysis showing higher po-
tassium and magnesium intakes were associated with greater
BMD at the hip and radius . Greater intakes of potassium
and magnesium were associated with less BMD loss at the hip
in men. Dietary intakes of potassium and magnesium were
similar across the sexes, suggesting that sex differences could
be due to differing hormonal changes with age.
Dietary acid load can be estimated by the net endogenous
acid production (NEAP), which includes dietary intakes of
protein, potassium, phosphorus, magnesium, and calcium to
calculate an estimate of dietary contribution to the overall
acid–base balance. It is theorized that chronic disruption of
the body’sacid–base balance would be detrimental to bone
health . One RCT showed pharmacologic doses of potas-
sium citrate (alkaline substance) to be beneficial to bone
health [57••]; however, two other RCTs showed no effect on
BMD [58,59]. Among men in the Framingham Original
Cohort, dietary acid load estimated by NEAP was inversely
related with femoral neck BMD, but no association was ob-
served at the spine; no significant associations were observed
in women . No associations between NEAP and BMD
were observed among men or women from the younger,
Framingham Offspring cohort. These results suggest that with
the possible exception of older men, dietary acid load as esti-
mated by dietary intake is not associated with BMD.
Overall, results from the Framingham studies show that
potassium and magnesium are positively related to bone
health, and these associations are likely independent of their
contribution to an alkaline state. Potassium may alter bone
metabolism by promoting calcium retention at the kidney
. Further, magnesium is essential for appropriate calcium
metabolism . Future research should examine interactions
between potassium, magnesium, and calcium intakes and also
examine long-term effects of an alkaline diet on fracture
The Framingham Osteoporosis Study has shown both men
and women with fish intakes ≥3 servings per week gain hip
BMD over 4 years compared to individuals with low to mod-
erate weekly fish intakes who lose BMD . Cross-sectional
studies in large cohorts of post-menopausal Chinese women
also support that habitual intake of fish is associated
with greater BMD [64,65]. The positive relation of fish
intake with BMD is likely due to many nutritional fac-
tors. In addition to protein (reviewed below), certain
seafood are high in polyunsaturated fatty acids (PUFA)
and, specifically, the n-3 fatty acid (FA) family, which
have been positively linked with bone health due to
their anti-inflammatory properties [66••].
Omega-3 Fatty Acids
Although total PUFA intakes have been positively linked with
bone health [67,68], the complex interactions between indi-
vidual FA and bone are gaining attention based on studies
published from the Framingham cohorts. In summary, no sig-
nificant associations were observed with intakes of individual
PUFA and BMD in either sex ; however, women whose
eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA)
intakes (both n-3 FA)≥median (0.14 g daily) had higher fem-
oral neck BMD with higher intake of the n-6 FA arachidonic
acid (AA). This interaction was also observed in men where
individuals in the highest quartile of AA intakes lost more hip
BMD than those with lowest intakes, but only among individ-
uals with low EPA+ DHA consumption. Therefore, the pro-
tective effects of a diet high in AA may be dependent upon
adequate EPA+DHA intakes. Also, plasma phosphatidylcho-
line (PC) concentrations of individual PUFA (n-3 FA DHA
and n-6 FA’s AA and linoleic acid) were related with femoral
neck BMD . The associations between individual PUFA
and BMD differed by sex. In women, no significant associa-
tions were observed; however, in men, a trend toward higher
BMD was seen with higher plasma PC AA.
The association between PUFA and risk of hip fracture
remains uncertain. In the Framingham Original cohort, dietary
alpha linolenic acid (ALA; n-3 FA) was protective against hip
fracture over 11 years of follow-up (54 % lower risk in the
highest vs. lowest quartile of intake) . In men, those in the
highest quartiles of AA intakes (n-6 FA) had an 80 % lower
risk of hip fracture than those in the lowest quartile of intake.
Men and women with the highest plasma AA concentrations
demonstrated 51 % lower hip fracture risk than those with the
lowest AA concentrations, supportive of the dietary associa-
tion observed only in men. These findings indicate that the
protective association of PUFA with bone health is complex.
Further insight is needed into the sex differences observed,
and well designed clinical trials are needed to elucidate wheth-
er bone health can be improved by greater fish intake and test
whether certain individual PUFA are driving these effects.
Dairy foods are a complex source of essential nutrients and
contribute to calcium, magnesium, vitamin D, vitamin B12,
zinc, riboflavin, and protein intake in the typical US diet .
Given that dairy foods are an essential resource of bone-
building nutrients, numerous studies have examined whether
dairy food intake (mainly milk) confers protection against
osteoporosis. Research on other dairy products such as yogurt,
cheese, and cream is limited. While several cross-sectional
studies have reported a positive link between childhood milk
consumption and bone density later in life [72–76], evidence
Curr Osteoporos Rep
for a beneficial role of milk intake on osteoporotic fracture is
less convincing [72,77,78,79••].
In the Framingham Offspring Study, the association of
milk, yogurt, cheese, cream, total dairy without cream, and
fluid dairy (milk+ yogurt) was examined with hip and spine
BMD . Higher intake of total dairy without cream was
associated with higher hip and spine BMD. Intake of fluid
dairy and milk was related to hip, but not spine BMD, while
yogurt intake was associated with trochanter BMD alone.
Cheese and cream intakes were not associated with BMD. In
final models, adjusting for other dairy products, yogurt intake
remained positively associated with trochanter BMD, while
cream tended to be negatively associated with femoral neck
BMD. In the same cohort, with 43 incident hip fractures over
12-year follow-up, no significant associations were observed
between dairy foods and hip fracture risk.
In subsequent analyses of dairy products and hip fracture
over 11 years of follow-up in the Framingham Original
Cohort, participants with medium (>1 and <7 servings/week)
or higher (≥7 servings/week) milk intake had 39 and 42 %
lower hip fracture risk, respectively, than those with low milk
(≤1 serving/week) intake [81••]. A threshold effect for milk
was reported, with 40 % lower hip fracture risk among those
with medium/high milk intake compared to those with low
intake. These associations were attenuated after adjustment
for femoral neck BMD, suggesting that greater intakes of milk
and milk+ yogurt may lower risk for hip fracture in older
adults through mechanisms that are partially, but not entirely,
attributable to effects on BMD. Not all dairy products may be
equally beneficial for the skeleton. Therefore, examination of
dairy foods other than milk and careful consideration of study
designs and confounding factors is necessary to reconcile the
divergent results, particularly from cohort studies of hip frac-
ture. Current knowledge on nutrients within dairy foods, such
as protein, potassium, and magnesium, is reviewed below for
likely links with bone.
Protein intake has been implicated in previous studies as being
both detrimental and beneficial to bone health . While
dietary protein has long been known to increase renal calcium
excretion and create negative calcium balance [83–85], many
population-based studies [86–92], but not all [93–97] have
shown that protein intake is beneficial for bone. Our work
from the Framingham Original cohort showed an association
between low protein intake and greater bone loss  and hip
fractures  in older adults. Similar positive associations
were also reported in the younger Framingham Offspring
women but not in men . Recent studies suggest that the
influence of protein on bone health may differ according to
calcium intake. In the Framingham Offspring Cohort, signif-
icant interactions were observed between percent energy from
protein intake and total calcium intake in women at all bone
sites , where protein was positively associated with BMD
only among women with low calcium intakes (<800 mg/day).
In longitudinal analyses, men with higher protein intakes had
more trochanter bone loss while no associations were seen in
women, regardless of calcium intake. Similar interactions
were also observed between animal protein intake and risk
of hip fracture, where men and women with calcium intakes
<800 mg/day had 2.8 times the risk of hip fracture in the
highest tertile of animal protein intake vs. the lowest tertile
. In the ≥800 mg calcium per day group, the highest
tertile of animal protein had an 85 % reduced hip fracture vs.
the lowest tertile of intake. Total protein intake was not asso-
ciated with hip fracture risk. These results suggest that greater
protein intake benefits BMD and protects against fracture risk
among adults with adequate calcium intake. Thus, calcium
intake modifies the association of dietary protein with bone
measures, which may explain the lack of concordance seen in
Alcohol Containing Beverages
Beer and Silicon
After oxygen, silicon is the most abundant element in the
earth’s crust. In the early 1970s, Carlisle and colleagues re-
ported that dietary silicon may contribute to bone mineraliza-
tion . In fact, studies in chickens demonstrated that bone
formation was impaired in diets deficient in silicon .
Silicon, as orthosilicic acid [Si(OH)4], is available from fluids
(such as drinking water and beer), and it was later determined
that silicon was also available from foods, in which it exists as
polymeric or phytolithic silica . The role of dietary sili-
con on bone health was further investigated in a cross-
sectional study of men and pre- and post-menopausal women
aged 30–87 years from the Framingham Offspring cohort
. We found silicon intake to be associated with BMD
in men and younger women; however, additional analyses
suggested that the association of beer intake and BMD was
in part accounted for by the silicon content of beer, which is
relatively high . Subsequently, a randomized trial of
choline-stabilized orthosilicic acid (silicon) supplementation,
as an adjunct to calcium/vitamin D3, showed that the
orthosilicic acid stimulated markers of bone formation in
osteopenic females .
Wine and Resveratrol
Findings from the Framingham Osteoporosis Study previous-
ly identified red wine as particularly beneficial to bone in
women . This finding led to speculation that resveratrol
may be a potential contributor to the association. Resveratrol
Curr Osteoporos Rep
is a naturally occurring polyphenolic compound that is rela-
tively abundant in red wine, grapes, and even nuts. It has
enjoyed a great deal of notoriety based on observations that
it increased longevity in animals . Salutary skeletal ef-
fects of resveratrol have been suggested based on observations
that it enhances osteoblast differentiation , inhibits oste-
oclast formation , and prevents bone loss in ovariecto-
mized animals . Resveratrol has been tested in a small
clinical trial of 74 middle-aged men, mean age 49 years with
metabolic syndrome who were randomized to 500 mg/day,
150 mg per day or placebo transresveratrol for 16 weeks.
There were significant increases in volumetric spine BMD
measured by QCT in the high dose group compared to place-
bo, but no differences for any other skeletal measures. At all
time-points during the 16 weeks of treatment, the higher dose
group had significantly greater increase in bone-specific alka-
line phosphatase from baseline compared with the placebo
A review of studies investigating alcohol intake and bone
health suggested a BJ^-shaped curve, where moderate inges-
tion of alcohol may offer maximum protection; however, in-
takes beyond this level show negative effects on the skeleton
. The above observations emerging from studies of alco-
hol containing beverages suggest that specific components
found in these beverages in addition to the alcohol may also
have effects on skeletal health.
Traditionally, nutrition research has focused on single nutri-
ents in relation to health. Yet, this approach is limited in that:
(1) it does not account for dietary quality or nutrient synergy
, (2) it cannot isolate individual effects due to high cor-
relation of nutrients within foods, and (3) the effect of a single
nutrient may be too small to detect . Most importantly,
isolating nutrients makes it difficult to translate results into
dietary recommendations. To overcome these limitations,
some investigators have proposed a Bdietary patterns^ap-
proach. Results from the Framingham Study Cohorts have
shown dietary patterns to be predictive of BMD among adults.
In the Framingham Original Cohort, six dietary patterns were
identified with the greatest proportions of energy intake from
the following groups: (1) meat, dairy, and bread; (2) meat and
sweet baked products; (3) sweet baked products; (4) alcohol;
(5) candy; (6) fruit, vegetables, and cereal . For men, the
fruit, vegetables, and cereal group had the greatest BMD
at all bone sites examined. The advantage of the fruit,
vegetables, and cereal group was not as clear in the
women, but their BMD tended to be higher than in other
groups. In both men and women, the candy group had
the lowest BMD at most sites.
As dietary protein is important for bone health, we have
recently examined patterns of dietary protein intake with bone
health. Protein-specific dietary patterns were created by clus-
ter analysis in the Offspring cohort. This type of cluster anal-
ysis is similar to methods of whole diet pattern analysis but
differs by clustering individuals based on their protein intakes
(% contribution of each food to total protein intake). Overall,
this study identified five protein food clusters, with the
greatest proportion of protein intake from: (1) chicken, (2)
fish, (3) processed foods (e.g., processed meats, pizza, and
french fries), (4) red meat, and (5) low-fat milk . Three
of these food clusters showed associations with BMD. In both
men and women, the red meat protein food cluster presented
with significantly lower femoral neck BMD compared to the
low-fat milk cluster. Further, the processed foods protein clus-
ter presented with significantly lower femoral neck BMD
compared to the low-fat milk cluster. A similar, yet non-
significant trend was observed for other BMD sites.
Data from other cohorts support the findings that diets rich
in fat and processed foods are detrimental to bone health in
Iranian  and Scottish populations , whereas diets
rich in fruits, vegetables, and fish are positively associated
with BMD . Although these studies show similar results
in how BMD varies across dietary patterns, statistical meth-
odologies used to determine these dietary patterns were dif-
ferent across the studies. Future research should focus on the
reproducibility of these dietary patterns while assessing die-
tary patterns with fracture outcomes and longitudinal changes
in bone across time. Research in dietary patterns and bone
health requires a more in-depth look at sex differences and
how changes in dietary pattern intakes across the lifespan
may alter bone health over time.
Nutrition Bone Genetics
With advances in genomic technology and personalized med-
icine, the fields of nutrigenomics and nutrigenetics have re-
cently emerged. Nutrigenomics is the study of how common
dietary ingredients influence the genome, whereas
nutrigenetics is the study of how an individual’s genetic make-
up influences one’s response to dietary intakes and how this
relates to various diseases. In the Framingham Osteoporosis
Study, several nutrigenetic studies have been conducted to
examine specific nutrient effects on the skeleton according
to genetic makeup. One of the earliest studies investigated
the interaction of polymorphisms in the vitamin D receptor
gene on the association between calcium intake and BMD.
In that early study, it was shown that calcium intakes above
800 mg per day were associated with higher BMD only in
individuals who had the bb genotype for the BsmIrestriction
fragment length polymorphism .
Curr Osteoporos Rep
Based on observations that B-vitamins may have effects on
skeletal health, and that genetic studies in Framingham had
identified suggestive linkage to bone measures on chromo-
some 1pter-1p36.3 , a region containing a potential can-
didate genes for bone status, (MTHFR gene), the Framingham
Study investigated the association between the C677T poly-
morphism in the methylenetetrahydrofolate reductase
(MTHFR) gene and bone phenotypes. BMD measures did
not differ between C677T groups. Although all participants
with plasma folate concentrations ≥4 ng/ml had ∼2 % higher
BMD than those with folate <4 ng/ml, the association disap-
peared after controlling for tHcy. Suggestive interactions be-
tween folate status and the C677T group (CC+CT vs. TT)
were found for hip BMD (p≤0.05) and BUA (p=0.11).
Compared with CC+ CT participants, TT individuals had low-
er mean BUA (p=0.06) and Ward’s area BMD (p=0.08) with-
in the folate<4 ng/ml group and significantly higherhip BMD
(p≤0.05) within the folate ≥4 ng/ml group. Thus, this study
demonstrated that the influence of a genetic polymorphism on
BMD was dependent on folate status.
Subsequently, the Framingham Osteoporosis study showed
that dietary fat intake had differential effects on BMD accord-
ing to variants in the peroxisome proliferator-activated recep-
tor gamma (PPARG) gene, as fat is known to be an endoge-
nous ligand of PPARG. These findings using epidemiologic
methods in the Framingham Study were corroborated in an
inbred mouse strain fed a high-fat diet .
As the goal of personalized medicine becomes more of a
reality, findings such as these from the Framingham
Osteoporosis Study suggest the possibility that nutrition will
also become personalized depending on one’s genetic
Dietary approaches can be an important strategy for the pre-
vention of osteoporosis. Emerging evidence indicates that diet
at the level of vitamins, minerals, food groups, and dietary
patterns play an important role in skeletal health. This review
presented our current understanding of the vitamins, minerals,
and macronutrients present within food groups and dietary
pattern as they relate to bone health in adults and older adults,
with a focus on the findings from the Framingham
Osteoporosis Study cross-sectional and prospective studies.
Several studies provide evidence for inclusion of fruits and
vegetables, seafood, specific dairy products, and alcohol con-
taining beverages, in moderation, for beneficial effects on
Further research comparing nutrients to dietary sources to
supplement use would advance our understanding of the un-
derlying mechanisms and aid in creating recommendations for
osteoporosis prevention. Prospective studies, in particular for
fracture outcome and controlled trials, are neededto determine
whether treatment with specific dietary supplements can im-
prove BMD or reduce fracture risk. Observational studies
have both supported and shown disagreement with controlled
trials. Longer-term prospective intervention studies are need-
ed to further examine the dietary effects on bone loss and
Acknowledgments DP Kiel received grant (R01 AR 41398) from Na-
tional Institute for Arthritis Musculoskeletal and Skin Diseases, during
the conduct of the study.
Compliance with Ethics Guidelines
Conflict of Interest S Sahni has received research grants from General
Mills Bell Institute of Health and Nutrition. KM Mangano declares no
conflicts of interest. RR McLean has received research grants from
General Mills Bell Institute of Health and Nutrition. MT Hannan has
received research grants from General Mills Bell Institute of Health and
Nutrition. DP Kiel declares no conflicts of interest.
Human and Animal Rights and Informed Consent All studies by S
Sahni, KM Mangano, RR McLean, MT Hannan, and DP Kiel involving
animal and/or human subjects were performed after approval by the ap-
propriate institutional review boards. When required, written informed
consent was obtained from all participants.
Papers of particular interest, published recently, have been
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