Diet and Osteoporosis

By James J. Kenney, PhD, RD, FACN. Copyright Food & Health

Communications, Inc. All Rights Reserved.

Diet and Osteoporosis............................................................................................1

Introduction..........................................................................................................1
Bone Physiology..................................................................................................2
Pathology of Osteoporosis...................................................................................3
Medical Diagnosis and Treatment of Osteoporosis.............................................4
Keeping Homocysteine Levels Low Is A Good Idea............................................5
Does Milk Do A Body Good?...............................................................................6
Who Should Take a Calcium Supplement?.........................................................7
Impact of Caffeine, Phosphorus and Protein.......................................................8
Excess Vitamin A May Increase Osteoporosis....................................................8
A Lack of Vitamin K May Contribute to Bone Loss..............................................9
Increased Potassium May Reduce Bone Loss....................................................9
Trace Minerals May Reduce Bone Density.......................................................10
A Little Fluoride Is Good But Is More Better?....................................................10
Dietary Salt Increases Bone Loss.....................................................................10
Tobacco and Alcohol..........................................................................................12
The Bottom Line.................................................................................................13
References:........................................................................................................13

Introduction
Osteoporosis is a medical condition that results in the loss of bone structure and
strength. It currently afflicts more than 25 million Americans putting them at
greatly increased risk of broken hips, wrists and collapsed vertebrae. About 1.5
million broken bones each year are attributed to osteoporosis and the medical
cost of treatment is in excess of $10 billion. About half of these fractures are to
back vertebrae, which can cause a lot of pain and deformity. There are also more
than 200,000 hip fractures annually in the US and these are often very
debilitating and can lead to long-term nursing home care.

Osteoporosis is a disease many health professionals will be seeing a lot more in

the decades ahead because the average age of the US population will continue
to rise. The loss of some bone mass appears to be partly a natural part of the
aging process itself. However, dietary and other lifestyle factors can slow down or
accelerate the loss of bone strength that occurs with increasing age.
Osteoporosis, like cardiovascular disease and diabetes, is associated with an
increased risk of dying. Osteoporosis weakens bones to the point where
relatively little trauma can cause a fracture. Both men and women who suffer a
low-trauma fracture have been shown to have an increased mortality rate. A 5-
year prospective cohort study in Australia found that all major fractures were

1
associated with increased mortality and the increase was even greater for men
than for women.1

Studies of fossilized human bone suggest that our ancient human ancestors
usually had a greater peak bone mass than modern men and women living in
industrialized societies today. Their loss of skeletal mass with age also appeared
to be considerably slower than that of modern people living in Westernized
societies.2 Part of the reason our ancient ancestor generally had stronger
skeletons throughout life than Americans today was their much greater level of
physical activity. The average American today is very sedentary compared to
Paleolithic humans. The bones of modern day hunter-gatherers are also
generally stronger on average than people living in more modern societies.
Research has shown that a sedentary lifestyle contributes to osteoporosis and
weight-bearing exercise like walking is associated with stronger bones. 3 One
year of strength training has been shown to increase bone mineral density (BMD)
in women 50-70y.4

It seems clear that the vast majority of Americans would have stronger bones
and a reduced risk of osteoporosis if they were more physically active. It should
be noted that while exercise is generally good for bone health, it could also cause
problems if excessive. Teenage girls involved in athletics, who diet frequently, are
at high risk for osteopenia (low bone mineral content), stress fractures and
broken bones, particularly if they also develop amenorrhea. Amenorrhea can
result from chronic dieting particularly if it leads to a severe eating disorder like
anorexia nervosa. Prolonged amenorrhea associated with dieting and/or
excessive exercise can lead to marked osteopenia, which probably greatly
increases the risk of early osteoporosis when these young females reach
menopause. Osteopenia can also develop in boys and young men who diet
frequently.

Genetic factors also influence skeletal strength. There are also racial differences
in the susceptibility of developing osteoporosis. People whose ancestors came
from sub-Saharan Africa in general tend to have a greater peak bone mass than
those whose ancestors came from Europe or Asia. However, osteoporosis occurs
in all human populations and tends to be more prevalent in people with smaller or
more slender bones. The risk for an individual is greater if their mother and/or
other close relatives developed osteoporosis at a fairly young age. It is clear that
the risk of developing osteoporosis is due in part to many different environmental
factors, which interact with genetic factors and the aging process.

Bone Physiology
There are 2 structural components of bone. One is the bone matrix (osteoid),
which is composed largely of collagen, but also contains other proteins such as
osteocalcin and ostepontin. The other component of bone is the minerals
deposited in this connective tissue matrix. These minerals are composed largely
of hydroxyapatite, which is a crystalline structure composed mostly of calcium

2
phosphate and calcium carbonate. These minerals provide the rigidity of bones
whereas the protein matrix supplies strength and some flexibility.

There are two major types of bone in the human body. About 80% of the bone
mass is tightly packed bone such as that in the shafts of the long bones of the
arms and legs. This is called cortical bone. Trabecular bone is much less dense
and composed of spicules that have a sponge-like appearance. Trabecular bone
has a large surface area and greater blood supply than cortical bone making it
more responsive to changes in circulating hormones (e.g., estrogen, parathyroid
hormone, calcitonin, testosterone) that can affect bone metabolism than cortical
bone. The vertebrae, small wrist bones and iliac crest of the hipbone are all rich
in trabecular bone that adds structural strength to the outer cortical bone. When
this structural material is lost in osteoporosis it sets the stage for low-trauma
fractures.

Bone is a living tissue that is constantly being built up and broken down. This
process is called remodeling and depends primarily on the function of two
different types of cells. One type of bone remodeling cells is the osteoblasts,
which are largely responsible for the build up of new bone tissue. The other type
of bone cell involved in remodeling is the osteoclasts whose role it is to break
down bone tissue. This breakdown of bone tissue is actually necessary to
maintain bone health because normal living results in small stress cracks, or
micro fractures, in the bone that over time could lead to larger fractures if the
damaged bone tissue is not being continuously remodeled.

Bone also serves as a source of stored minerals (especially calcium). When the
diet does not contain enough calcium to maintain blood levels it can be released
from the bone. Serum calcium must be maintained between a fairly narrow range
or muscle cramping (tetany) or calcification of soft tissues can occur. There are
several hormones that regulate serum calcium levels that also affect the bone
remodeling process. Parathyroid hormone (PTH) is released from the parathyroid
glands when serum calcium levels start to fall too low. The release of PTH results
in the release of calcium from the bone by stimulating osteoclast activity. PTH
also reduces calcium excretion in the urine. Calcitrol (1,25 dihydroxyvitamin D) is
produced from vitamin D in a two-step process involving the liver and kidneys. It
acts to enhance calcium absorption from the gut. Calcitonin is released in
response to a rise in serum calcium and directly inhibits the osteoclasts and
slows the breakdown of bone minerals. Estrogen appears to function by inhibiting
the action of PTH on osteoclasts.

In children, the growth of new bone exceeds bone breakdown. During this stage
of life the osteoblast create new bone faster than the osteoclasts are breaking it
down. Around age 30y most people attain what is called peak bone mass. By age
40y the activity of the osteoblasts starts to slow down to the point where new
bone formation falls behind the breakdown of old bone by the osteoclasts. It is
primarily the drop in osteoblast cell activity with age that sets the stage for

3
osteoporosis. The result is that bone mass starts to decline in all people with
increasing age. For several years after menopause women experience a marked
decline in bone mass of at least 1-2% per year. As much as 5-7% of BMD can be
lost the first year or two after menopause starts. The average loss of bone for
older women (10 years past menopause) slows to about 0.5% per year, which is
similar to that of older men.

Pathology of Osteoporosis
Age is probably the most important predictor of BMD. This loss of BMD weakens
bone to the point where even a minor trauma can result in a major fracture.
Women are more likely to develop osteoporosis than men for 3 main reasons. 1.
Women normally have a lower peak bone mass than men. 2. Women experience
an accelerated loss of bone following the hormonal changes associated with
menopause. 3. Women generally live longer than men so they continue to
experience the bone loss associated with aging for a longer time. The result is
women end up with a lower BMD in their last 10-20 years of life much more
frequently than men. They have a much greater risk of broken bones over their
lifetime. Nevertheless, it would be a mistake to believe that men are not at risk for
osteoporosis. All men experience a considerable loss of bone by the time they
are in their 70's and 80's. With better control of cardiovascular disease risk
factors many more men can expected to live long enough to develop
osteoporosis and suffer a broken bone as a result in the future. Even today about
20% of all osteoporosis related fractures occur in men.

The second most important predictor of osteoporosis is genetic factors, which

may account for as much as 70% of the variation in BMD of people the same sex
and age.5 Some drugs can cause a significant loss of BMD if taken for prolonged
periods (See Table 1, below).

Table 1. Drugs That Increase Bone Loss

Corticosteroids Lithium
Phenytoin (Dilantin) Tetracycline
Phenobarbital Thyroid Hormone
Heparin Methotrexate
Aluminum-Containing Antacids Cyclosporin
Phenothiazine Derivatives
________________________________________________________________
___________

One major difference between the risk of developing osteoporosis and that of
developing most other common degenerative diseases such as Type 2 diabetes
mellitus, atherosclerosis and hypertension is that being overweight is associated
with a decreased risk of developing osteoporosis. The risk of most other
degenerative diseases increases with increasing body mass index (BMI).

4
However, BMD increases with increasing body weight. Therefore, the risk of
osteoporosis is somewhat reduced in overweight and obese individuals
compared to those who are normal weight or underweight. Body weight has less
impact on bones that are not weight bearing. The difference in BMD of the wrist
bones of overweight and lean individuals is less than for weight bearing bones in
the back, hips and legs. The benefits of increased body weight in terms of
fractures is partially offset by the greater stress placed on bones in falls. Of
course, no one would advocate gaining a lot of weight to prevent bone loss
because the benefits would be more than offset by an increased risk of morbidity
and mortality from CVD, diabetes, gallstones, some types of cancer, etc.

Very thin young women who have amenorrhea are at a higher risk for broken
bones.6 The gain of some body fat in very thin girls and young women will help to
increase peak bone mass and probably reduce the risk of osteoporosis later in
life. This is because amenorrhea appears to result primarily from very low body
fat stores. The use of an estrogen containing "contraceptive" pill in girls with
amenorrhea is probably medically justifiable to increase peak bone mass until
sufficient body fat is gained to restore a normal reproductive cycle.

It should also be kept in mind that while there are treatments for osteoporosis
that can strengthen bone somewhat (at least in the short-run) and reduce the risk
of fractures, there is no safe and effective treatment that can entirely replace
bone lost to osteoporosis. As with all degenerative diseases an "ounce of
prevention" is by far the most cost effective public health strategy for reducing the
morbidity, mortality as well as the social and economic costs of osteoporosis.

Medical Diagnosis and Treatment of Osteoporosis

Osteoporosis, like high blood pressure and atherosclerosis, is often without
symptoms until the disease process is far advanced. Even though there are tests
to accurately measure BMD and diagnose the loss of BMD long before the loss
of bone puts someone at very high risk of broken bones, many doctors are still
reluctant to order such screening tests, even in patients with a number of risk
factors. The result is that a broken hip, wrist or ruptured vertebrae becomes the
way advanced osteoporosis is first discovered. Dual-energy X-ray absorptiometry
(DXA) remains the gold standard for assessing BMD, diagnosing osteoporosis
and assessing the rate of progression of osteoporosis. 7 DXA can also be used to
screen for people who are at high risk of developing osteoporosis due to below
average BMD. A much cheaper but somewhat less accurate measure of BMD
than DXA is an ultrasound-scanning device that measure bone density in the
heel in about 10-15 seconds. Because of its low cost, ultrasound scanning of
bone density of the heel is appropriate for community screening and use in a
doctor's office. Just as finding a high cholesterol level or high blood pressure in a
patient can often help motivate him/her to improve his/her diet and lifestyle, so
too can finding below average BMD for one's age.

5
There are a number of drugs that can be used to treat and/or help prevent
osteoporosis. Calcitonin, which inhibits bone resorption by osteoclast, appears to
be most effective if given early in menopause. Calcitonin cannot be taken in pill
form because of its peptide structure. However, it can now be delivered via a
nasal spray as well as injection. Calcitrol, which is the active form of vitamin D,
can be quite toxic and can dangerously elevate serum calcium levels. Patients
receiving this drug must have their serum calcium closely monitored to avoid
hypercalcemia. Its use can probably only be justified in patients receiving long-
term glucocorticoids which markedly increase the risk of bone loss. Calcifidiol is a
safer form of vitamin D and can also be used to enhance calcium absorption and
slow bone breakdown with much less danger of hypercalcemia.

Estrogen therapy may modestly increase the risk of breast cancer so many
women would prefer not to take it. However, it has been shown to be quite
effective at preventing the rapid loss of bone that occurs during the first 5-10
years after menopause. Women who took estrogen for seven or more years after
menopause were shown to have significantly greater BMD up to age 75y
compared to women who did not take estrogen (+11.2% greater). However, after
age 75y the impact of even long-term estrogen therapy was only 3.2% greater
BMD compared to women who did not take estrogen. 8 Testosterone can help
increase bone formation in men with low BMD and low testosterone levels. It is
most helpful in men being treated with corticosteroids, which depress
testosterone production. Thiazide diuretics can also help reduce the loss of bone
in both men and women who are taking corticosteroids.

For women who are at higher risk of breast cancer, or those who do not wish to
take estrogen replacement after menopause, there is a new class of drugs called
selective estrogen receptor modulators (SERMs), which can be considered.
Tamoxifin can be used to treat breast cancer patients who also have
osteoporosis because it has been shown to help conserve bone. However,
because Tamoxifen has undesirable side effects it is not appropriate for treating
or preventing osteoporosis. Raloxifene, another SERM, has been approved by
the FDA for treating osteoporosis, because it appears to help prevent bone loss. 9
Isoflavones found in soy products appear to act somewhat like SERM and have
shown some potential in reducing bone loss.10 While there is a lot of media hype
about the use of soy products and even isolated soy isoflavones to treat
osteoporosis there is insufficient evidence at this time to warrant the use of
isolated soy isoflavone supplements to treat osteoporosis. However, the use of
soymilk fortified with calcium and vitamin D (and cobalamin) is a sensible
substitution for cow's milk in the diet of vegans or people who do not wish to
consume cow's milk.

Biphosphonates (Etidronate, Alendronate, Risedronate), which are chemically

related to pyrophosphate act by inhibiting osteoclast activity and slowing the
breakdown of bone. Biphosponates have been shown to both increase BMD 11, 12
and also to reduce the risk of fractures.13 The bone formed in the treatment of

6
osteoporosis with biphophonates appears to be histologically normal and overall
safety was similar to that of a placebo. 14 Biphosphatonates can cause
esophageal reflux making them difficult for some patients to take. To minimize the
risk of esophageal difficulties Fosomax (alendronate) should be taken with a full
glass of plain water 30 minutes before consuming breakfast or a beverage like
coffee. It should not be taken before bed or lying down. Fosomax has been
approved for preventing as well as treating osteoporosis in high-risk women with
below normal BMD.

Another promising treatment for healing broken bones was recently approved by
the FDA (Orthofix's Physio-Stim). This system uses a weak electrical current to
stimulate the healing of fractures. A similar devise is now being tested to see if an
electrical current can stimulate the growth of bone in patients with osteoporosis.
We will now take a look at how dietary variables can impact the risk of
developing osteoporosis. It is important that a healthy diet be adopted early in life
because it along with appropriate exercise will enable an individual to attain the
greatest possible peak bone mass given their genetic make-up.

Keeping Homocysteine Levels Low Is A Good Idea

For many years doctors have known that people very high levels of
homocysteine in their blood often develop severe osteoporosis early in life. Even
moderately elevated levels of homocysteine in fasting blood are strongly
associated with an increased risk of cardiovascular disease. As homocysteine
levels rise above 9mg/dl the risk of heart attacks, strokes and developing of
Alzheimers disease goes up. There is already more than enough reason to take
steps to lower the homocysteine level in the blood if it is moderately elevated but
until the results of a new study were published in the New England Journal of
Medicine in May there was no good evidence to suggests lowering homocysteine
levels might also prevent damage to the bones leading to hip fractures.

Hip fractures are the number one cause of elderly people being forced into
nursing homes. Researchers in Holland examined the risk of hip fractures in men
and women age 55 and older. After several years of follow-up they found that the
people whose homocysteine level was in the top 25% were twice as likely to
suffer a hip fracture as those whose homocysteine levels were in the bottom 25%
of the group. The authors of this study conclude An increased homocyteine
levels appears to be a strong and independent risk factor for osteoporotic
fracture in older men and women. 15

Supplements of folic acid, vitamin B-6, vitamin B-12 and either choline and/or
betaine can lower elevated homocysteine levels. By contrast diets high in fatty
meats and particularly processed meats like hot dogs, sausages, bologna and
pepperoni raise blood pressure, cholesterol levels and markedly increase the
level of homocysteine in the blood particularly for several hours after every high
protein meal. Fasting homocyteine levels and LDL levels are also elevated in

7
people who eat more fatty animal products and fewer whole grains, fruits,
vegetables and nonfat dairy products.

There is already convincing evidence that lowering high cholesterol levels

reduces the risk of osteoporosis and hip fractures. This new data demonstrating
a strong connection between modestly elevated homocysteine levels and an
increased risk in hip fractures provides yet another reason to discourage
Americans from following fad diets high in protein, salt and animal fats and low in
fruits, vegetables, whole grains, and legumes.

Does Milk Do A Body Good?

There are a number of dietary factors, which contribute to the development of
strong bones by age 30 y or so. These same dietary factors also contribute to the
loss of BMD with increasing age. In addition to a much more active lifestyle, our
ancient ancestors also consumed a diet that was drastically different than that of
modern day Americans. It seems likely that some of these dietary differences
could be contributing to the weaker bones of modern day humans. One of the
most obvious differences between the diet of modern day Americans and that of
our ancient ancestors was the consumption of milk. Some people have argued
that our ancient ancestors had much stronger bones on average than do modern
day Americans today, in part because they did not drink milk.

The most obvious and well publicized of the dietary factors associated with
weaker bones is a lack of calcium. Another possible factor contributing to the loss
of BMD is the excessive intake of protein and particularly animal protein. This
may be due primarily to the higher content of sulfur-containing amino acids found
in animal proteins compared with proteins from plants. Since vegetable proteins
tend to be lower in sulfur-containing amino acids they appear to have much less
effect on urinary calcium excretion than sulfur-rich animal proteins. 16 It could be
argued that our ancient ancestors had much stronger bones on average than
does the average American today and they did not drink milk. However, their diet
was much higher in both calcium and protein than that of Americans.

While milk is fairly high in sulfur-containing amino acids, claims that it may
increase the risk of osteoporosis do not appear accurate. Indeed, previous milk
consumption in young women has been associated with greater bone density. 17 A
study of 843 Chinese women found that BMD was positively associated with
calcium from dairy products. Indeed, the connection between dairy product
calcium and stronger bones was even stronger than for calcium from other
sources.18 This may be because some high calcium vegetables like spinach and
rhubarb are high in oxalic acid, which prevents most of the calcium from being
absorbed.

People who do not get outdoors and do not drink milk or vitamin D fortified
soymilk, may be at increased risk of osteoporosis. This may be due not only to a
lower intake of calcium but also because they generally have a much lower

8
intake of vitamin D than people who consume milk. Research has shown lower
serum 25-OH vitamin D (the metabolically active form of vitamin D) and higher
levels of parathyroid hormone (usually associated with the mobilization and loss
of bone calcium) in middle-aged vegans compared to vegetarians that include
dairy products in their diets, particularly in the winter months. 19 People who live in
high northern latitudes and do not drink milk should be encouraged to take a
vitamin D supplement during the winter months. People that do not consume
many calcium-rich leafy vegetables like collards and kale may also benefit from a
calcium supplement.

It seems clear that most research suggests that drinking milk is more likely to
decrease the risk of osteoporosis despite the fact that some of its constituents if
consumed in excessive amounts may have a negative impact on BMD. However,
the large amount of saturated fat and cholesterol found in whole milk clearly raise
serum cholesterol and increase the risk of atherosclerotic heart disease and
stroke. The bones of most Americans would likely be stronger if they regularly
consumed 2 servings of nonfat milk daily. Other dairy products are good sources
of calcium but unlike milk they are not fortified with vitamin D.

What About Protein?

One of the most hotly debated controversies in clinical nutrition today is whether
a diet higher in protein has a positive or negative effective on bone strength and
bone mineral density (BMD).
Those who are against protein point to the fact that vegetarians tend to have
stronger bones than people who eat more meat and the clinical trials showing
increased loss of calcium in the urine when meat or protein intake is increased.
On the other hand, those who believe more protein is beneficial to bone strength
point to clinical trials in which children who consume more protein tend to build
stronger bones than those who consume less.
In some studies of older Americans who consumed more protein, the risk of bone
fracture was reduced.
Our Ancient Ancestors Had Strong Bones
If we look at this problem from an evolutionary perspective, two things are clear.
First, from the fossils of our ancient ancestors, it is clear that their bones were far
stronger on average than those of Americans today.
Second, our ancient ancestors were for the most part hunter-gatherers and ate a
diet that was likely considerably higher in protein than the diet of most
Americans.
The bones of our closest relatives, the great apes, consume a much more
vegetarian diet than our ancestors did and yet their bones are stronger still.

9
Our ancient ancestors had stronger bones in part because they were much more
physically active than modern people today. Also their diets differed in many
other ways which impact bone strength than simply being higher in protein.
A recent study examined the long-term impact of dietary protein and other factors
on bone development in children from 6 to 18 years. It showed that while higher
protein intake was generally associated with stronger bones, the beneficial
impact of more protein in the diet was greatly diminished if the diet had relatively
little alkalinizing minerals (calcium, potassium, magnesium). 20
Fruits and vegetables are very high in potassium and also can have a lot of
calcium and/or magnesium.
These minerals oppose the acids that form from the metabolism of protein-rich
foods that are high in phosphorus and sulfur. These are metabolized to sulfate
and phosphates, which make the urine more acid. In addition these foods can
generate more uric acid.
Normal metabolism generates lactic acid and other organic acids that tend to
acidify the urine.
Grains also on balance tend to result in more acid that alkaline in the blood and
urine when metabolized, although not as much as most animal products.
Potatoes and yams have more of an alkalizing effect than grains, even when
those grains are whole.
Most high protein foods of animal origin such as cheese, meat, fish, poultry and
eggs generate more acidity in the body.
Increased dietary salt is known to increase the loss of calcium in the urine even
though its impact on the acid-base balance in the body is neutral because
sodium is a strong base but chloride is a strong acid. One way to cut the net acid
load on the body is to replace added salt in the diet with MSG. Research has
shown that replacing sodium from salt with MSG results in far less acidic urine
and also cuts the loss of calcium in the urine, which should reduce not only the
risk of osteoporosis but also most kidney stones.
Bottom line: While research now shows that diets with more protein do help
strengthen bones, it is also very important to get enough calcium, potassium and
magnesium by eating more fruits and vegetables. It is also important to minimize
the foods that tend to generate excess acidity like refined grains, processed
meats, and cheeses. Reducing salt helps reduce calcium excretion and replacing
it with MSG alkalanizes the urine, which should help strengthen bones A diet low
in meat, cheese, eggs, salt and refined grains and much higher in fruits,
vegetables, and with MSG in place of salt, can be used to alkalinize the urine and
reduce the risk of osteoporosis and most kidney stones.

10
Who Should Take a Calcium Supplement?
People who cannot or do not wish to consume milk regularly may find it very
difficult to meet the recommended calcium intake of 1200 to 1300 mg for some
age groups. The average calcium intake for women in America is only about 500
mg/day. Perhaps the best calcium supplement for children and young adults is
calcium carbonate because it has the highest ratio of calcium to the anion of all
calcium supplements. Bone meal and dolomite calcium supplements are best
avoided as they may be contaminated with lead, cadmium or other heavy metals.
Chewable sources of calcium, such Tums, may be appropriate for those who
cannot swallow pills. There is also a calcium supplement in the form of a
chocolate candy cube that may be appropriate for some individuals (Viactiv).

Older people who have achlorhydria (about 15-20% of those 60y +) will often do
better with a calcium citrate supplement because it is less dependent on stomach
acid than calcium carbonate for absorption. Younger people and older people
with normal stomach acidity absorb calcium carbonate nearly as efficiently as
calcium citrate. Calcium citrate tends to be a little less constipating than calcium
carbonate. It should be noted that calcium supplements could reduce the
absorption of iron, zinc, manganese and other divalent cations. A deficiency of
these trace minerals may contribute to osteoporosis or other nutritional problems.
Also, to ensure adequate calcium absorption is important that adequate vitamin
D stores be maintained either by diet, supplementation or sunlight. The diet of
most people who shun milk will not contain adequate vitamin D to meet their
needs.

How much calcium one should take as a supplement depends on his/her dietary
intake of calcium. It also depends on the amount of other substances in the diet,
which influence calcium absorption and/or excretion. It is likely that the amount of
calcium needed could be reduced if the American diet were not so high in salt,
soft drinks and other caffeine-rich beverages, and foods with an acidic residue
such as meats. As we shall see, these dietary factors can all increase the loss of
calcium from the body.

One problem with calcium supplements is that those that are poorly formulated
may not dissolve and simply pass through the digestive tract. A simple test can
help determine if a calcium supplement may be difficult to absorb. Place the
supplement in a glass with warm vinegar for about 15 minutes. After that time it
should be breaking up and should fall apart fairly easily if pressed with a spoon. If
it remains very hard then it may not be well absorbed.

While calcium supplements may be of some benefit in individuals with a poor

diet, there is no way supplements can be a substitute for a healthier diet with
more fruits, vegetables, whole grains, legumes, nonfat dairy products and a little
seafood. Such foods contain trace minerals, vitamins and other phytochemicals
that may help maintain adequate BMD into old age. Calcium supplements are
probably warranted in treating people with osteoporosis who are also taking

11
prescription drugs in an attempt to strengthen remaining bone and reduce the
risk of fractures.

Daily supplements of 500 mg of calcium and 700 IU (17.5 mcg) of vitamin D have
been shown to reduce bone loss and the incidence of broken bones in older men
and women.21 It appears that supplements of calcium and vitamin D may help
reduce the risk of broken bones in older Americans. It is also likely that a calcium
supplement in teenagers who shun dairy products may help to increase peak
bone mass, which should also help delay the development of osteoporosis when
they reach old age. However, BMD can be impacted by many dietary factors
besides calcium and vitamin D and avoiding osteoporosis may depend as much
on what is avoided as what is consumed.

A vitamin D intake up to 2000 IU or 50 mcg is safe for nearly everyone. Total

body sun exposure can easily supply 10,000 IU so even higher doses up to this
level may be safe except for hypersentive individuals. 22

A calcium intake up to 2000 mg daily appears to be safe for most people. 23

However, even 1000 mg of calcium supplementation may increase constipation
in some people. Also, high doses of supplemental calcium may reduce the
absorption of iron, zinc and other trace minerals.

Calcium and Vitamin D supplements are not proven to prevent fractures. The US
Preventive Task Force recommends:24
The Task Force recommends against daily supplements of less than 400
IU of vitamin D3 and less than 1,000 mg of calcium for the prevention of
fractures in postmenopausal women.

The Task Force found that the current evidence is insufficient to make a
recommendation on daily supplements greater than 400 IU of vitamin D3
and greater than 1,000 mg of calcium for the prevention of fractures in
postmenopausal women.

The Task Force found that the current evidence is also insufficient to make
a recommendation on vitamin D and calcium supplements for the
prevention of fractures for men and premenopausal women.

Impact of Caffeine, Phosphorus and Protein

A heavy consumption of caffeine may also contribute to an increased loss of
calcium from the body and thus contribute to bone loss over time. A study of 205
healthy nonsmoking, post-menopausal women found that those who were
consuming less than 800 mg of calcium daily and were also consuming more
than 450 mg of caffeine daily had a lower BMD than the women who consumed
more calcium and/or less caffeine.25 However, other researchers have failed to

12
find a consistent association between dietary caffeine intake and the loss of
bone.26 Moderate intake of caffeine is certainly not a major factor in the
development of osteoporosis. However, the lifetime intake of the amount of
caffeine in as little as 2 cups of coffee per day is associated with decreased BMD
in older women. The negative impact of caffeine on BMD was greatest in those
women who did not consume milk on a daily basis. 27 Women, who are at high
risk for future bone loss and get less than the RDA of calcium, should probably
be advised to limit caffeine intake.

Soft drinks are often high in both phosphorus and caffeine. They are becoming
an increasingly popular beverage for girls and young women, often displacing
milk from the diet. Consuming a diet high in phosphorus and low in calcium has
been shown to result in elevated parathyroid hormone (PTH) secretion. 28
However, the role played by dietary phosphorus in BMD appears to be
complicated. Increased dietary phosphorus has actually been shown to help
prevent the increased loss of calcium normally seen with the increased intake of
dietary sulfur-containing amino acids. 29 However, high intakes of both protein and
phosphorus have been associated with a lower BMD in young women. 30 A diet
high in meat, with the regular use soft drinks instead of nonfat milk as a
beverage, will likely reduce peak bone mass in the young and increase the risk of
developing osteoporosis in later years. The ancestral diet of humans was
generally higher in calcium, phosphorus and protein than that of modern day
Americans. More research is needed to sort out the long-term impact of diets
high in protein, phosphorus and calcium on BMD and the risk of fractures.

Excess Vitamin A May Increase Osteoporosis

The highest rates of osteoporosis and hip fractures in the world are in Norway
and Sweden.31 Indeed the rate of hip fractures in these two countries is 7 times
higher than that in other European countries. 32 These two countries also have a
very high intake of milk and milk products. Sweden fortifies all low and nonfat
dairy products with retinol or vitamin A at about twice the level at which it is found
in whole milk. In addition, retinol is added to margarine and there is also a lot of
retinol in cod liver oil, which is a commonly used supplement in these countries.
The result is that the intake of retinol intake in Norway and Sweden is about 6
times higher than in most other European countries and it is this excessive intake
of retinol (>1.5 mg or 5,000/d) that may be contributing to osteoporosis in Norway
and Sweden.33

More research is clearly needed to confirm the link between excessive intake of
vitamin A and an increased loss of bone mass. As people grow older they appear
to have a lower capacity to clear high levels of ingested retinol from the body. 34
Based on current evidence it seems prudent to advise people at risk of
osteoporosis to limit their intake of pre-formed vitamin A (retinol) to the RDA level
of 800 RE or 0.8 mg of retinol per day. This means food supplements with retinol
should be avoided, as should supplements of cod liver oil. It also means avoiding
liver and not consuming too many servings of dairy products and particularly

13
those, which have been fortified with retinol. There is no evidence that vitamin A
from plants (as beta-carotene and other carotenoids) increases the risk of
osteoporosis although high doses of beta-carotene may be toxic.

It should also be noted that most of the best dietary sources of vitamin D are also
high in retinol. These include milk, eggs, liver and fatty fish. Also most
multivitamins contain both retinol and vitamin D. Since the recommended intake
of vitamin D for older Americans is so high (400 IU.) and most of the best food
sources of vitamin D are high in retinol, it may be prudent to encourage older
people to spend 10-15 minutes in the sun (without a sunscreen) several times a
week. Sunscreens block UV light, which is necessary for the conversion of
cholesterol to vitamin D in sun exposed skin. Those who live in northern states
should take a vitamin D supplement with about 200-300 IU. of vitamin D daily
during the winter months because sunlight contains insufficient UV light to make
vitamin D during this time and body stores of vitamin D can drop too low after 2-3
months of inadequate intake. Those who are house bound or in a nursing home
and cannot get regular exposure to UV light should take a similar supplement
year round. It should be noted that an excessive intake of vitamin D (more than
2000 IU daily) could be toxic and damage the kidneys and cause calcification of
soft tissues.

A Lack of Vitamin K May Contribute to Bone Loss

When most people think of vitamin K, they think of its role in blood clotting.
However, vitamin K mediates the gamma-carboxylation of glutamyl residues on
several different bone proteins, most notably osteocalcin. 35 Osteocalcin is an
important bone matrix protein synthesized by the osteoblasts and appears to be
involved in the mineralization of the matrix. Many elderly people have a low
intake of vitamin K, primarily because they eat few dark green leafy vegetables. 36
Many elderly people may take antibiotics that reduce the formation of vitamin K
by the microflora of the gut. Others may be taking coumidin or other
anticoagulants and have been told to avoid vitamin K rich foods and supplements
as these may increase the risk of blood clots.

Increased vitamin K intake is associated with a decreased loss of calcium in the

urine.37 Undercarboxylated osteocalcin in the serum has been associated with
reduced levels of vitamin K and lower BMD. A prospective analysis of the Nurses'
Health Study Cohort found that low intakes of vitamin K were associated with an
increased risk of hip fracture in these women.38 While most Americans probably
get close to the recommended amount of vitamin K (80 mcg) it is not clear that
this is optimal for healthy bone formation and maintenance. The RDA was
determined to be adequate for normal blood clotting but the optimal amount of
vitamin K for bone formation may be several times higher. More research is
needed to determine the optimal intake of vitamin K for older people to help slow
the loss of bone.

14
Most people have heard it is important to get enough calcium and vitamin D to
grow and maintain strong bones that can resist fracture but few have heard of the
bone strengthening effects of vitamin K. There are two main forms of vitamin K.
Vitamin K1 is called phyoquinone or phytonadione and is found mainly in green
vegetables like spinach, broccoli, lettuce, and kale. Vitamin K2 is made up of
menaquinones that can be synthesized in the human gut by micro-organisms.
There are several kinds of these menaquinones and small amounts occur in
meats and fermented products like cheeses and natto. However, about 90% of
the vitamin K in the American diet comes from vegetables. There is also a
synthetic form of vitamin K3 but it is not recommended for human consumption.

People who have heard of vitamin K may be familiar with its important role in
blood coagulation but few realize it is also necessary for making a protein called
osteocalcin. Osteocalcin is a protein needed to bind calcium to the bone matrix.
An inadequate intake of vitamin K may reduce this protein to the point where
bone mineral density is reduced and bone structure is compromised.

A recent meta-analysis examined 7 studies in which elderly subjects were given

either 15 (one study) or 45mg of vitamin K2 or a placebo. Remarkably those
taking the supplements of vitamin K had reductions in hip fractures of 77%
compared to those given a placebo. Fractures of the vertebrae were cut by 60%
and all other fractures were reduced by 81%. None of the individual studies
reported any serious side effects from the vitamin K supplements although there
did appear to be some increase in GI problems. The authors of this study
conclude From a clinical perspective, the results of this review suggest that
patients at risk for fractures should be encouraged to consume a diet rich in
vitamin K, which is chiefly obtained from green leafy vegetables and certain
vegetable oils.

Increased Potassium May Reduce Bone Loss

The metabolism of the typical American diet with its high intake of meat and low
intake of fruits and vegetables tends to yield an excess of endogenous acid. The
human skeleton serves as a reservoir of calcium that can be mobilized to prevent
the blood pH from dropping too low (becoming too acidic). Long ago it was
hypothesized that the mobilization of bone minerals to buffer excessive acid in
the blood could contribute to an increased loss of bone over time and
osteoporosis.39 In postmenopausal women, oral potassium bicarbonate at a dose
sufficient to neutralize endogenous acid improves calcium and phosphorus
balance increases bone formation and reduces the rate at which bone is
resorbed.40 It seems likely that an increased intake of fruits and vegetables with
their high potassium intake may help prevent osteoporosis.

Back in 1968, Drs. Wachman and Bernstein theorized that the elevated renal
acid load from meat, cheese, grains, and phosphate-rich foods may contribute to
the development of osteoporosis.41 They suggested consuming more vegetables
and fruits would reduce the acid load on the body and limit the loss of calcium

15
being lost in the urine to buffer the increased renal acid load. A study by Dr.
Dawson-Hughes examined the impact of adding either sodium or potassium
bicarbonate supplements to neutralize the increased renal acid load produced by
a typical modern diet in 171 subjects age 50 and older. They found both
alkalizing supplements reduced urinary calcium and urinary N-telopeptide a
marker for more rapid bone breakdown. Dr. Dawson-Hughes concluded that
alkalinizing the urine had a favorable effect on bone resorption and calcium
excretion. This suggests increasing the alkali content of the diet may attenuate
bone loss in healthy older adults.42 Another study that examined the impact of
dietary protein and other factors on bone development in children from 6 to 18
years showed that while higher protein intake was generally associated with
stronger bones, the beneficial impact of more protein in the diet was greatly
diminished if the diet was lower in alkalinizing minerals (i.e., calcium, potassium,
magnesium).43
A study published online by Dr. Jehle and colleagues examined the impact of
giving 201 healthy older people (>65y) either 60mEq of potassium citrate or a
look alike placebo for two years. All subjects also received supplements of
vitamin D and calcium. After 2 years, only those receiving the potassium
supplement saw a reduction in their renal acid load and experienced a significant
increase in their bone mineral density (BMD). 44Those receiving the placebo saw
no change or modest declines in BMD. It is likely then consuming more
potassium-rich foods and cutting back on cheese, meats, and phosphate-rich
foods and drinks would help alkalinize the blood and urine and likely slow or even
partially reverse the loss of bone minerals associated with osteoporosis. While
salt has little impact on acid-base balance, it also contributes to increased urinary
calcium loss and so should also be limited in diet of those at risk for
osteoporosis. Replacing some salt with MSG would also reduce renal acid load
and calcium excretion.
Bottom Line: Americans should consume more potassium-rich foods like fruits
and vegetables to help stop or reverse bone loss. It is important to cut back on
foods like meats, eggs, cheeses, sodas, etc. that acidify the blood and urine and
contribute to the loss of BMD over time. Those who already have weakened
bones may also benefit from replacing even some of the whole grain products in
their diets with more potatoes and yams as the latter are much higher in
potassium and would reduce their renal acid load and the loss of BMD.

Trace Minerals May Reduce Bone Density

A diet rich in refined fats and oils and/or sugar, white flour and other refined
carbohydrates will be much lower in many essential trace minerals than the diet
consumed by our ancient ancestors during the evolution of man. An increased
consumption of fruits and vegetables, which are excellent sources of both
potassium, vitamin K, magnesium and trace minerals involved in bone
metabolism in older men and women was shown to contribute to the
maintenance of BMD in a 4 year longitudinal study. 45 It is clear that people at risk
for osteoporosis should be encouraged to consume more fruits and vegetables.

16
Boron appears to be used by osteoblasts in bone formation and seems to mimic
some of the effects of estrogen.46 A supplement of 3 mg daily of boron was
shown to increase beta-estradial and testosterone levels in older subjects. Boron
appears to reduce the excretion of calcium, phosphorus and magnesium in the
urine, particularly when the diet is low in magnesium. Boron's function in bone
formation appears to be related to magnesium metabolism. 47 Whether or not
boron is absolutely required for healthy bone formation in humans is still a matter
of some debate. Boron is a required mineral for fruiting plants so consuming a
diet with plenty of fruits and vegetables should supply adequate boron. Legumes
and nuts are also good sources of boron. There is no evidence that levels of
boron in excess of what one would already get from a healthy diet are beneficial,
so a boron supplement would be of questionable value.

A low serum magnesium level, which is often seen in patients with chronic
alcoholism, diabetes mellitus and malabsorption syndromes (e.g., celiac disease
and Crohn's disease) appears to be a risk factor for the development of
osteoporosis and osteomalacia.48 49 Whole grains, legumes and dark green
vegetables are the best dietary sources of magnesium and supply trace minerals
and other factors that may improve bone health. Diets low in copper may
contribute to osteoporosis by interfering with the formation of the protein support
structure for new bone.50 Iron is another trace mineral involved in bone
metabolism. It serves as a catalytic co-factor for ascorbic acid in the
hydroxylation of proline and lysine, which is necessary for the maturation of the
collagen matrix. In theory, a deficiency of either iron or vitamin C, could lead to a
weaker bone matrix but there are no studies, which suggest that a lack of either
of these nutrients plays a role in the development of osteoporosis.

Zinc, copper, manganese, and fluoride are al involved in the formation of healthy
bone. One study of postmenopausal women found that the addition of these 4
minerals to a calcium supplement helped slow the loss bone in these older
women.51 More research is needed to determine the amount of various trace
minerals necessary for optimal bone health. However, it seems likely that a
modern Western diet with a lot of refined foods may result in low enough intakes
of some essential minerals to undermine the formation and remodeling of healthy
bones.

A Little Fluoride Is Good But Is More Better?

In the past high intakes of fluoride supplements (e.g. 75 mg/d) were believed to
build stronger bone. Mega doses of fluoride do increase BMD. However, while a
large dose of fluoride increase BMD there is also evidence that bone with an
excessive fluoride content is more susceptible to micro fractures because of
alterations in the structure of the hydroxyapatite (where fluoride atoms displace
hydroxyl ions). Fluoride may make bone more rigid and brittle and is not likely to
reduce the overall fracture rate in people with osteoporosis. 52 In any case, since
high doses of fluoride can cause nausea, gastric bleeding and vomiting and may

17
even increase the risk of hip fracture53 and all fractures.54 Clearly more research
is needed before high-dose fluoride supplements can be accepted as a useful
treatment of osteoporosis.

Dietary Salt Increases Bone Loss

One of the most important factors contributing to an increased loss of calcium in
the urine and the development of osteoporosis has been widely ignored by most
clinicians and the mass media. The scientific evidence is very consistent that
excessive intake of dietary salt greatly increases the loss of calcium in the urine.
Increased salt intake has also been associated with reduced peak bone mass
and a more rapid loss of BMD in older people. It is hard to escape the conclusion
that the amount of salt added to commercial foods and at home in all modern
societies must play a major role in the development of ostepenia and eventually
osteoporosis. It seems likely that dramatically reducing dietary salt would help
prevent many broken bones in America every year. One must increase the intake
of dietary calcium by approximately 1000 mg daily to prevent bone loss in
postmenopausal women who are ingesting an extra 2000 mg of sodium as salt
daily.55 Results of a longitudinal study suggested that reducing dietary sodium
excretion by 50% (from 3450 to 1725 mg/d) would be as effective in slowing the
loss of bone as increasing dietary calcium by 891 mg/d. 56

A study in New Zealand showed that there was a progressive increase in urinary
calcium excretion as dietary salt intake increased from 70 to 220 mmol/d (or
about 1600 to 5000 mg of sodium). Data from this study suggested that reducing
dietary sodium from 5000 to 1600 mg daily would reduce the loss of calcium in
the urine by 32% in men and 27% in women.57 Simply put, the more salt you eat,
the more calcium you'll excrete.

However, it should be noted that the problem with increased urinary excretion of
calcium with increased dietary salt is not caused by the sodium ion alone. Even
5500 mg of sodium when given as either sodium citrate or sodium bicarbonate
did not increase urinary calcium excretion as sodium chloride does. Using low-
sodium baking powder (which contains potassium bicarbonate) in place of
regular baking powder (which contain sodium bicarbonate) will also help to
reduce urinary calcium excretion and presumably also the loss of BMD. 58 Those
concerned with either the development of essential hypertension or osteoporosis
would also be better advised to consume MSG rather than salt or sea salt. 59

It has been shown that both a lack of calcium and/or an excess of salt in the diet
leads to a reduction in bone density in young females. 60 In postmenopausal
women, an increase in dietary salt has been shown to increase urinary calcium
excretion61 and lead to an increased loss of bone minerals. 62 While increased
dietary phosphate can blunt the increased calcium excretion caused by a high
protein intake, increased dietary phosphate has no impact on the increased
excretion of calcium caused by adding more salt to the diet. 63

18
An excessive intake of dietary salt is the primary causal factor in the
development of essential hypertension.64 High blood pressure is also associated
with increased bone loss in elderly white women.65 While there is no prospective
human data on the long-term impact of reducing dietary salt on BMD, the data
showing a strong correlation between urinary sodium and both urinary calcium
and urinary hydroxyproline (a marker for bone loss) certainly suggests that the
unnaturally high intake of salt in all modern human populations plays a major role
in the development of osteoporosis.66 Because older Americans will develop
either high blood pressure, osteoporosis or both it is perplexing that the media
and most health professionals do not more strongly encourage people to reduce
their salt intake. A low salt intake combined with a diet higher in fruits,
vegetables, whole grains and nonfat dairy products (DASH-style diet) should
slow the loss of bone mineral density as people age by improving bone
metabolism.

Low-Sodium DASH Diet Improves Bone Metabolism

Epidemiological studies have found that people who consume more fruits and
vegetables tend to have stronger bones.67 In addition numerous studies have
shown that increasing dietary salt intake leads to an increased loss of calcium in
the urine and an increased serum parathyroid hormone level. 68 In theory, it
seems likely that combining a DASH-style diet with a low sodium intake should
improve bone metabolism and may help prevent the development of
osteoporosis.

A recent studied examined the combined impact of either the DASH diet versus a
more conventional American diet each fed with 3 different levels of dietary
sodium intake. The DASH- Sodium trial enabled researchers to examine the
impact of 3 different levels dietary salt (50, 100 & 150mmol of Sodium/day) with
either a typical American diet or with the DASH diet. Compared to a typical
Americican diet the DASH diet contains more whole grains, fruits, vegetables and
low-fat dairy products and less meat and other foods high in saturated fat as well
as less sugar and refined carbohydrates. This new study specifically examined
the individual and combined impact of different levels sodium intake and
consuming the DASH diet on bone metabolism. Switching from a typical
American diet to the DASH diet resulted in about a 10% reduction in osteocalcin,
a hormone associated with more rapid breakdown of bone. Another marker of
bone breakdown called C-terminal telopeptide of type 1 collagen (CTX) was also
about 16-18% lower on the DASH diet than the more typical American diet.
However, urinary calcium loss was not significantly increased on the American
diet compared to the DASH diet. Increasing dietary sodium (as salt) was
associated with a greater loss of calcium in the urine on both the DASH diet and
the more typical American diet. Urinary calcium excretion was increased
somewhat more on the typical American diet than on the DASH diet. Calcium
excretion was also increased significantly more with increasing dietary salt in
subjects with high blood pressure compared to those who were normotensive.

19
The authors of this study conclude, the DASH diet significantly reduced bone
turnover, which if sustained may improve bone mineral status. A reduced sodium
intake reduced calcium excretion in both diet groups and serum osteocalcin in
the DASH group. The DASH diet and reduced sodium intake may have
complementary, beneficial effects on bone health. 69 Given the fact that most
older Americans have or will soon develop hypertension and that most are also at
risk of developing osteoporosis it seems prudent to encourage all older
Americans to adopt a low-sodium DASH-style diet.

Tobacco and Alcohol

Smoking cigarettes has long been known to contribute to osteoporosis in part
because smokers are thinner and lower BMI is associated with lower BMD. 70 A
meta-analysis of 48 studies showed that the more a women smoked, the greater
her risk of fracture.71 The impact of alcohol on bone loss and the risk of fractures
is more complicated. Clearly, even moderate intake of alcohol can increase the
risk of falls and thus increase the risk of a broken bone. However, moderate
alcohol consumption appears if anything to reduce the loss of BMD. Heavy
drinking contributes to both bone loss and fractures. 72 Moderate alcohol
consumption may increase estrogen levels and this may not only be part of the
reason it increases BMD but also why it has been associated with an increased
risk of breast cancer.73 Once recent study, published in the American Journal of
Epidemiology, found that moderate alcohol intake (11-20 g/day) was associated
with a significant increase in trochanteric bone mineral density in elderly women
compared with no alcohol intake. But the beneficial effect of alcohol on bone
mineral density was no longer apparent at alcohol intake above the moderate
level, or about 1-3 glasses of wine, 3-7 glasses of beer or 1-3 shots of liquor per
day or a combination of these. Total bone mineral density was significantly lower
in women with alcohol intake of 30g/day or more compared with non-drinkers. 74

The Bottom Line

Osteoporosis is a disease characterized by the gradual loss of bone mass with
age. Its development is influenced by genetic factors as well as by dietary and
other lifestyle factors. A diet high in salt, animal protein (which increases
endogenous acid production) and caffeine will likely increase the loss of calcium
in the urine. An excessive intake of phosphorus, retinol, alcohol and fluoride may
also increase the risk of bone fractures but more research is needed to
determine how much is too much. In addition, the typical American diet often
lacks adequate calcium, magnesium, potassium, vitamins K & D and perhaps
trace minerals such as zinc, boron, manganese and copper for optimal bone
health. Smoking and inactivity also increase the risk of osteoporosis, as do some
prescription and over-the-counter drugs.

A diet lower in salt, soft drinks and meat and high in fruits and vegetables with 2-
3 servings of nonfat milk daily coupled with an active lifestyle (with plenty of
weight bearing exercise) is probably best for preventing osteoporosis and bone

20
fractures. A reduction in dietary salt and animal protein will reduce the loss of
calcium in the urine and help maintain adequate BMD into old age. However,
once osteoporosis is established, dietary treatment alone is insufficient to
minimize the risk of bone fractures although a healthy diet should remain a
valuable adjunctive therapy for people with osteoporosis who are taking drugs
such estrogen or alendronate to strengthen bones. Supplements of calcium,
vitamin D and perhaps other nutrients should be considered when the patient
does not comply with a healthy diet prescription.

References:

21
1
Center JR, Nguyen TV, Schneider D, et al. Mortality after all major types of osteoporotic fracture in men and women: an
observational study. Lancet 1999;353:878-82
2
Eaton SB and Nelson DA. Calcium in evolutionary perspective. Am J Clin Nutr 1991;54:281S-7S
3
Krall EA, Dawson-Hughes B. Walking is related to bone density and rates of bone loss. Am J Med 1994;96:20-6
4
Nelson ME, Fiatarone MA, Morganti CM, et al. Effects of high-intensity strength training on multiple risk factors for
osteoporotic fractures. JAMA 1994;272: 1909-14
5
Johnston CC, Smelenda C, Melton LJ. Changes in skeletal tissue during the aging process. Nutr Rev 1992;50:385-8
6
Goulding A, et al. Bone mineral density in girls with forearm fractures. J Bone Min Res 1998;13:143-7
7
Slovik DM, Adams JS, Neer RM, et al. Deficient production of 1,25 dihydroxy vitamin D in elderly osteoporotic patients
N Engl J Med 1981;305:372-4
8
Felson DT, Zhang Y, Hannan MT, et al. The effect of postmenopausal estrogen therapy on bone density in elderly women.
N Engl J Med 1993;329:1141-6
9
Delmas PD, et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, uterine contractions,
and uterine endometrium in postmenopausal women. N Engl J Med 1997;337:1641-4
10
Anderson JJB, Garner SC. The effects of phytoestrogens on bone. Nutr Res 1997;17:1617-23
11
Harris ST, Watts NB, Jackson RD, et al. Four-year study of intermittent cyclic etidronate treatment of postmenopausal
osteoporosis: Three years of blinded therapy followed by one year of open therapy. Am J Med 1993;95:557-66
12
Miller PD, et al. Cyclical etidronate in the treatment of postmenopausal women: Efficacy and safety after seven years of
treatment. Am J Med 1997;103:468-74
13
Lieberman U, et al. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal
osteoporosis. N Engl J Med 1995;333:1437-41
14
Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: A
randomized controlled trail. JAMA 1999;282:1344-52
15
van Meurs JBJ, Dhonukshe-Rutten RAM, Pluijm SMF, et al. Homocysteine levels and the risk of osteoporotic fracture. N
Engl J Med 2004;350:2033-41
16
Kaneko K, Masaki U, Aikyo M, et al. Urinary calcium and calcium balance in young women affected by high protein diet
of soy protein isolate and adding sulfur-containing amino acids and/or potassium. J Nutr Sci Vitaminol 1990;36:105-16
17
Teegarden D, Lyle RM, Proulx WR, et al. Previous milk consumption is associated with greater bone density in young
women. Am J Clin Nutr 1999;69:1014-7
18
Hu J-F, Z X-H, Jia J-B et al. Dietary calcium and bone density among middle-aged and elderly women in China. Am J
Clin Nutr 1993;58:219-27
19
Lamberg-Allardt C, Karkkainen M, Seppanen R, Bistrom H. Low serum 25-hydroxyvitamin D concentrations and
secondary hyperparathyroidism in middle-aged white strict vegetarians. Am J Clin Nutr 1993;58:684-9
20
1AmJClinNutr2005;82:110714
21
O'Brien. Combined calcium and vitamin D supplementation reduces bone loss and fracture incidence in older men and
women. Nutr Rev 1998;56:148-58
22
Vieth R.Vitamin D supplementation, 25-hyroxyvitamin D concentrations and safety. Am J Clin Nutr 1999;69:842-56
23
NIH Consensus Development Panel on Otimal Calcium Intake. Optimal Calcium intake. JAMA 1994;272:1942-8
24
http://www.uspreventiveservicestaskforce.org/bulletins/vitdbulletin.pdf
25
Harris SS, Dawson-Hughes B. Caffeine and bone loss in healthy postmenopausal women. Am J Clin Nutr 1994;60:573-8
26
Lloyd T, Rollings N, Eggli DF, et al. Dietary caffeine intake and bone status of menopausal women. Am J Clin Nutr
1997;65:1826-30
27
Barrett-Connor E, Chang JC, Edelstein SL. Coffee-associated osteoporosis offset by daily milk consumption. JAMA
1994;271:280-3
28
Calvo MS, Kumar R, Heath H. Persistently elevated parathyroid hormone secretion and action in young women after four
weeks of ingesting high phosphorus, low calcium diets. J Clin Endocrinol Metab 1990;70:1334-40
29
Zemel MB, Schuette SA, Hegsted M, Linkswiler HM. Role of the sulfur-containing amino acids in protein-induced
hypercalciuria in men. J Nutr 1981;111:545-52
30
Metz JA, Anderson JJB, Gallagher PN. Intakes of calcium, phosphorus, and protein, and physical activity level are related
to radial bone mass in young adult women. Am J Clin Nutr 1993;58:537-42
31
Maggi S, Kelsey JL, Litvak J, Heyse SP. Incidence of hip fractures in the elderly: a cross-national analysis. Osteoporos Int
1991;1:232-41
32
Johnell O, Gullberg B, Allander E, Kanis JA. The apparent incidence of hip fracture in Europe: a study of national
registered sources. MEDOS Study Group. Osteoporos Int 1992;2:298-302
33
Melhus H, Michaelsson K, Kindmark A, et al. Excessive dietary intake of vitamin A is associated with reduced bone
mineral density and increased risk for hip fracture. Ann Intern Med 1998;129:770-8
34
Whiting SJ, Lemke B, Excess retinol intake may explain the high incidence of osteoporosis in northern Europe. Nutr Rev
1999 57:1925
35
Suttie JW. Vitamin K-dependent carboxylase. Annu Rev Biochem 1995;54:459-77
36
Kohlmeier M, et al. Vitamin K: A vegetarian promoter of bone health. Vegetarian Nutr 1997;1:53-5
37
Kon-Siong GJ, Hamulyak K Gijsbers BL, et al. Effects of vitamin K and oral anticoagulants on urinary calcium excretion.
Br J Haematol 1993;83:100-4
38
Feskanich D, Weber P, Willett WC, et al. Vitamin K intake and hip fractures in women: a prospective study. Am J Clin
Nutr 1999;69:74-9
39
Wachman A, Bernstein DS. Diet and osteoporosis. Lancet 1968;1:958-9
40
Sebastian A, Harris ST, Ottaway JH, et al. Improved mineral balance and skeletal metabolism in postmenopausal women
treated with potassium bicarbonate. N Engl J Med 1994;330:1776-81
41
Lancet 1968;1:958-9
42
JClinMetab.2009;94:96102
43
Am J Clin Nutr 2005;82:1107-14
44
J Clin Endocrin & Metabdoi:10.12/j c.2012-3099
45
Tucker KL, Hannan MT, Chen H, et al. Potassium, magnesium, and fruit and vegetable intakes are associated with greater
bone mineral density in elderly men and women. Am J Clin Nutr 1999;69:727-36
46
Nielson FH, et al. Boron enhances and mimics some of the effects of estrogen therapy in postmenopausal women. J Trace
Elements Exp Med 1992;5:237-42
47
Hunt CD, et al. Metabolic responses of postmenopausal women to supplemental dietary boron and aluminum during usual
and low magnesium intake: Boron, calcium and magnesium absorption and retention and blood mineral concentrations. Am
J Clin Nutr 1997;65:803-9
48
Al-Ghamdi SM, Cameron EC, Sutton RA. Magnesium deficiency pathophysiologic and clinical overview. Am J Kidney
Dis 1994;24:737-52
49
Rude RK, Olrich M. Magnesium deficiency: possible role in osteoporosis associated with gluten-sensitive enteropathy.
Osteoporos 1996;6:453-61
50
Klevay LM. Lack of a RDA for copper may be hazardous to your health. J Am Col Nutr 1998;17:322-6
51
Strause L, Saltman P, Smith KT, et al. Spinal bone loss in postmenopausal women supplemented with calcium and trace
minerals. J Nutr 1994;124:1060-4
52
Riggs BL, Hodgson SF, O'Fallon WM, et al. N Engl J Med 1990;322-802-9
53
Hedlund LR, Gallagher JC. Bone Min Res 1989;4:223-7
54
Pak C, et al. Slow-release sodium fluoride in the management of postmenopausal osteoporosis: a randomized controlled
trial. Ann Intern Med 1994;120:625-9
55
Massey LK, Whiting SJ. Dietary salt, urinary calcium, and bone loss. J Bone Miner Res 1996;11:731-6
56
Devine A, Criddle RA, Dick IM, et al. A longitudinal study of the effect of sodium and calcium intakes on regional bone
density in postmenopausal women. Am J Clin Nutr 1995;62:740-5
57
Goulding A. Fasting urinary sodium/creatinine in relation to calcium/creatinine and hydroxyproline/creatinine in a general
population of women NZ Med J 1981;93:294-7 and Goulding A. Osteoporosis: why consuming less sodium chloride helps
conserve bone. NZ Med J 1990;103:120-2
58
Lemann J, Gray RW, Pleuss JA. Potassium bicarbonate, but not sodium bicarbonate, reduces urinary calcium excretion
and improves calcium balance in healthy men. Kidney Int 1989;35:688-95
59
Kurtz TW, Al-Bander HA, Morris RC. Salt sensitive essential hypertension in men. Is the sodium ion alone important? N
Engl J Med 1987;317:1043-8
60
Matkovic V, Illich JZ, Andon MB, et al. Urinary calcium, sodium, and bone mass in young females. Am J Clin Nutr
1995;62:417-25
61
Zarkadas M et al. Sodium Chloride supplementation and urinary calcium excretion in postmenopausal women. Am J Clin
Nutr 1989;50:1088-94
62
Devine A, Criddle RA, Dick IM, et al. A longitudinal study of the effect of sodium and calcium intakes on regional bone
density in postmenopausal women. Am J Clin Nutr 1995;62::740-5
63
Whiting SJ, Anderson DJ, Weeks SJ. Calciuric effects of protein and potassium bicarbonate but not sodium chloride or
phosphate can be detected acutely in adult women and men. Am J Clin Nutr 1997;65:1465-72
64
Kenney JJ. Salt: Has it been given a fair shake? Or is it a serial killer? www.foodandhealth.com/cpecourses/salt.htm
65
Cappacino FP, Meilahn E, Zmuda JM, et al. High blood pressure and bone-mineral loss in elderly white women: A
prospective study. Lancet 1999;354:971-5
66
Jones G, Beard T, Parameswaren V, et al. A population-based study of the relationship between salt intake, bone
resorption and bone mass. Eur J Clin Nutr 1997;51:561-65
67
New SA, Robins SP, Campbell MK, et al. Dietary influences on bone mass and bone metabolism: further evidence of a
positive link between fruit and vegetable consumption and bone health? Am J Clin Nutr 2000; 71:142-51
68
Massey L, Whiting S. Dietary salt, urinary calcium and bone loss. J Bone Miner Res 1996;11:731-6
69
Pao-HWA L, Ginty F, Appel LJ, et al. The DASH diet and sodium reduction improve markers of bone turnover and
calcium metabolism in adults. J Nutr 2003;133:3130-6
70
Slemeda CW, HUI SL, Langcope C, Johnston CC Jr. Cigarette smoking, obesity, and bone mass. J Bone Miner Res
1989;4:737-41
71
Law MR, Hachshaw AK. A meta-analysis of smoking, bone mineral density and the risk of hip fracture: Recognition of a
major effect. Br Med J 1997;315:841-7
72
Heaney RP. Bone mass, nutrition, and other lifestyle factors. Am J Med 1993;95(suppl 5A): 29S-33S
73
Hankinson SE, Willett WC, Manson JE, et al. Alcohol, height, and adiposity in relation to estrogen and prolactin levels in
postmenopausal women. J Natl Cancer Inst 1995;87:1297-302
74
Baudoin et al. Am J Epidemiol 2000;151:773-780