National Osteoporosis Foundation
Volume III, Issue 2
OSTEOPOROSIS
CLINICAL UPDATES
Editorial Boar d
OVER-THE-COUNTER PRODUCTS &
OSTEOPOROSIS: CASE DISCUSSIONS
Angelo Licata, MD, PhD, FACP, FACE
Editor-in-Chief
Research Director, Metabolic Bone Disease Clinic
Cleveland Clinic Foundation
Osteoporosis is a complex multifactorial condition affected by a spectrum of
biochemical and biomechanical factors.
Lawrence G. Raisz, MD
Senior Editorial Consultant
Professor of Medicine
University of Connecticut Health Center
Louise Acheson, MD, MS
Associate Professor of Family Medicine
Case Western Reserve University and
University Hospitals of Cleveland
Richard Bauer, MD
Chief of Staff
South Texas Veterans Health Care System
Carolyn J. Bolognese, RN
Clinical Nurse Specialist
Bethesda Health Research
Peggy Doheny, PhD, RN, ONC
Associate Professor, College of Nursing
Kent State University
Susan L. Greenspan, MD
Professor of Medicine
University of Pittsburgh School of Medicine
Anthony B. Hodsman, MD
Professor, Department of Medicine,
Division of Nephrology
University of Western Ontario
Barbara Lukert, MD, FACP
Professor of Medicine
University of Kansas Medical Center
Michael Maricic, MD
Chief, Section on Rheumatology
Southern Arizona VA Health Care System
Paul D. Miller, MD
Medical Director, Colorado Center
for Bone Research
Clinical Professor of Medicine, University of
Colorado Health Sciences Center
Morris Notelovitz, MD
Consultant, Adult Women’s Medicine
Gainesville, Florida
Karen A. Roberto, PhD
Professor & Director, Center for Gerontology
Virginia Polytechnic Institute and State University
Carol Sedlak, PhD, RN, ONC
Associate Professor, College of Nursing
Kent State University
Kathy M. Shipp, PhD, PT, MHS
Assistant Research Professor
Department of Community and Family Health,
Division of Physical Therapy
Duke University Medical Center
Guest Reviewer
Bess Dawson-Hughes, MD
USDA Human Nutrition Research Center on Aging
Tufts University
Osteoporosis: Clinical Updates is published by the
National Osteoporosis Foundation (NOF). The
views and observations presented in Osteoporosis:
Clinical Updates are those of the authors/editors
and do not reflect those of the funders or producers
of this publication. Readers are urged to consult
current prescribing and clinical practice information on any drug, device, or procedure discussed in
this publication.
There has been much promising research in the field of prevention and treatment.
One result of this has been to raise expectations among the public that a wide
range of products, from dietary supplements to topical hormone creams, can have a
positive impact on bone health. In this issue of Osteoporosis: Clinical Updates, we
will look at a variety of over-the-counter preparations promoted for the “treatment”
and “prevention” of osteoporosis and review the evidence for their effectiveness.
CASE 1: 55-YEAR-OLD WOMAN
he first patient we will discuss is a 55-year-old woman who is
three years postmenopausal with no history of fracture.
T
The patient presents for her yearly physical exam. She reports that her
75-year-old mother recently broke a hip after slipping on ice and is
worried that she, herself, may be at risk.
Given her family history, is this patient at risk for osteo porosis?
Yes. History of fragility fracture in a first-degree relative is an established risk factor for osteoporosis.
The patient reports that she has been using topical progesterone cream
and oral soy supplements for prevention of bone loss. She asks if she
should be doing anything else.
What are the effectiveness of topical progesterone cream
and soy supplements for preventing osteoporosis?
There has been very little clinical research on the effectiveness of
many over-the-counter (OTC) products on the market that promote
themselves as treatments or preventatives for osteoporosis.
Neither of the OTC products the patient is using has been shown in
clinical trials to prevent osteoporosis or osteoporotic fracture.
Isoflavone, a component of soy, has been demonstrated to have a mild
estrogenic effect on bone and on the cardiovascular system in women
who consume approximately 50 or more mg per day. The patient’s
National Osteoporosis Foundation • 1232 22nd Street,
N.W. • Washington,DC 20037-1292 • (202) 223-2226 • Copyright
©
2002 • All rights reser ved
tially harmful effects on bone in patients on long courses
of retinoids for skin diseases.1,2
intake of supplements may have a benefit, if her intake is
50 mg or more per day. Clinical trials have shown progesterone creams to have no beneficial effect on bone health.
While neither OTC product the patient is using has been
proven to help prevent osteoporosis, neither has been
shown to cause harm in recommended doses. However,
there is solid scientific evidence that adequate calcium
and vitamin D intake can slow the rate of bone loss.
In addition, recent research suggests that ingestion of supplemental retinol, found in high concentrations in fish oil,
can significantly increase a woman’s risk of hip fracture.
(RR 1.48 for ≥ 10,000 IU/day). The same increase in risk
was not found for intake of vitamin A from beta carotene
(see page 4).
How can a physician easily estimate if this patient
is getting adequate calcium and vitamin D?
Should the patient be advised to curtail use of
Accutane? Fish oil supplements?
The physician can quickly establish if the patient gets
adequate calcium by asking how many servings of dairy
products she has each day, multiplying this number by
300, adding 250 mg for nondairy dietary calcium sources,
and then adding the calcium in any multivitamin or
supplement taken.
The benefits to the patient of continuing use of Accutane
must be weighed against the possible increased risk of
osteoporosis. She reports having severe acne without use
of the drug. The physician advises that she continue with
the Accutane but have a DXA scan now and follow up
with DXA every f ive years to measure and monitor her
bone density.
The physician queries the patient on calcium intake and
sun exposure to determine if supplements are needed.
After estimating the patient’s daily calcium intake, the
physician recommends a daily calcium supplement to
bring the patient’s average intake up to 1200 mg/day.
Because the patient takes a daily multivitamin that contains vitamin D (400 IU) and participates regularly in
outdoor activities, the physician does not recommend
additional vitamin D supplementation.
The potential cardiovascular benefit of fish oil supplements (for their omega-3 fatty acid content) are most
likely offset by their potential harm to the patient’s bones.
The physician recommends that the patient discontinue
intake of fish oil supplements and that she limit her intake
of vitamin A in multivitamins to the beta carotene form.
Animal and epidemiological studies have indicated that
omega-3 fatty acids from nonretinol sources such as flax
seed oil may have a positive impact on bone health (see
page 5).
CASE 2: 35-YEAR-OLD WOMAN
Should the physician discourage continued use
of supplemental magnesium, zinc, and soy?
The second patient we will discuss is a 35-year-old
woman with no family history of osteoporosis. The
patient has been taking Accutane (isotretinoin) for 10
years to treat acne. In addition, when the physician takes
her medical history, the patient reports that she takes multiple nutritional supplements, including fish oil, flax seed
oil, magnesium, zinc, and soy.
Not if they are kept within safe tolerable limits: 350
mg/day for magnesium and 40 mg/day for zinc. Because
zinc and magnesium are involved in healthy bone metabolism, it is possible that intake of these minerals may be
beneficial to bone. However, research is lacking to support this hypothesis. Research on soy, as discussed above,
has suggested a mild benefit to bone.
Is this patient at increased risk for osteoporosis?
The physician recommends a daily calcium supplement.
In addition, the physician cautions that there is limited
data to support claims of bone health benefits from supplemental flax seed oil, soy, zinc, and magnesium.
She may be. Clinical research has demonstrated poten-
Estimating Daily Dietary Calcium Intake
Product
Milk (8 oz)
Fortified citrus juice (8 oz)
Fortified cereal (no milk),
snacks, etc.
Fortified cereal with
4 oz milk
Yogurt (8 oz)
Cheese (1 oz)
# of Servings
Calcium Content
Total calcium
(mg)
x
x
300mg/serving =
300mg/serving =
________________
________________
x
100mg/serving =
________________
x
x
x
250mg/serving =
400mg/serving =
200mg/serving =
(for nondairy sources)
________________
________________
________________
+ 250 mg
TOTAL
CASE 3: 70-YEAR-OLD WOMAN
The third patient we will discuss is a house-bound elderly
woman, 70 years old, who has low bone hip and spine
density on DXA (osteopenia), but not osteoporosis.
What dietary issues can the patient address to
help maintain her bone health?
_____________
❷
OTC VITAMINS, MINERALS, TRACE
ELEMENTS, AND OTHER NUTRIENTS:
IMPACT ON BONE HEALTH
How to Take Calcium
The body can best handle about 500 mg of calcium at any
one time, whether from food or supplements. Therefore,
calcium-rich foods and/or supplements should be consumed in small doses throughout the day, preferably with a
meal. Multiple-tablet doses can easily be split, with the
first tablet taken at lunch and the second at dinner.
Because the body requires calcium 24 hours a day, some
experts suggest consuming a calcium-rich food such as
yogurt or a calcium supplement at bedtime to provide a
calcium source
during the night.
The recommended daily allowances, adequate intakes, and
tolerable upper limits cited in this newsletter are taken
from the Dietary Reference Intakes (DRIs) established by
the Food and Nutrition Board of the Institute of Medicine,
1997–2001. When insufficient data exist for establishing a
recommended daily intake level, adequate intake levels
are indicated, representing the median intakes reported
from the Food and Drug Administration Total Diet Study.
Vitamins, Minerals, and Trace Elements
Adequate calcium, vitamin D, and protein intake have all
been shown to significantly benefit bone health in elderly
women. They alone will not prevent osteoporosis, but they
are necessary components of an overall prevention or
treatment plan.
Calcium. Calcium is essential for blood clotting, nerve
function, and countless other metabolic processes. It is
also essential for building and maintaining a healthy
skeleton. Ninety-nine percent of the body’s calcium
reserve is stored in bone. Serum calcium balance is tightly regulated by parathyroid hormone (PTH), calcitriol,
and calcitonin. Because the body cannot produce calcium,
calcium lost through the gastrointestinal tract, kidneys,
and skin must be replaced through the diet. When serum
calcium levels are too low, and adequate calcium is not
provided by the diet, calcium is taken from bone. Longterm calcium deficiency is a known risk factor for osteoporosis. The recommended daily calcium intake is 1000
for people aged 19 to 50 and 1200 for people older than
50 with a tolerable upper limit of 2500 mg/day.
Because of her lack of sun exposure, it is probably safe to
assume that this patient is vitamin D deficient. Vitamin D
deficiency contributes significantly to bone loss. To establish serum calcium and 25-hydroxy vitamin D levels, the
physician runs a blood chemistry.
The patient is advised to take a daily supplement that contains adequate vitamin D (400 IU) and calcium (1200
mg). In addition, she is advised to maintain an adequate
intake of protein (50 grams/day).
Adequate calcium intake is necessary for attaining peak
bone mass in early life (until about age 30) and for slowing the rate of bone loss in later life.1 Although calcium
alone (or with vitamin D) has not been shown to prevent
estrogen-related bone loss, multiple studies have found
calcium consumption between 650 and over 1400 mg/day
reduces bone loss and increases lumbar spine BMD.2, 3, 4
Are there any other measures that this patient
can take to help preserve her bone mass?
Immobilization is an established risk factor for bone loss
and osteoporosis. The patient is referred to a physical
therapist to develop a safe movement/exercise plan to ease
the patient into bone-preserving weight-bearing exercises
that she may perform at home.
The physician discusses drugs approved for osteoporosis
prevention and recommends that the patient consider
beginning drug therapy to prevent further bone loss.
Recommended Calcium Intakes*
Ages
Birth – 6 months
6 months – 1 year
1–3
4–8
9–13
14–18
19–30
31–50
51–70
70 or older
References
1.
2.
Okada N, Nomura M, Morimoto S, Ogihara T, Yoshikawa K. Bone mineral
density of the lumbar spine in psoriatic patients with long-term etretinate
therapy. J Dermatol. 1994;21:308-11.
Kindmark A, Rollman O, Mallmin H, Petren-Mallmin M, Ljunghall S,
Melhus H. Oral isotretinoin therapy in severe acne induces transient suppression of biochemical markers of bone turnover and calcium homeostasis. Acta Derm Venereol. 1998;78:266-9.
Pregnant & Lactating
14–18
19–50
Amount mg/day
210
270
500
800
1300
1300
1000
1000
1200
1200
1300
1000
*Source: National Academy of Sciences (NAS)
❸
Vitamin D deficiency can be a problem among individuals who avoid sunlight, do not drink vitamin D fortified
milk, do not take a multivitamin containing vitamin D, or
are homebound or institutionalized, are on dialysis or
anticonvulsive medication, or suffer from diabetes,
hypertension, chronic neurological disorders, or gastrointestinal diseases. In addition, research on hospital inpatients found a significant degree of vitamin D deficiency
(42%) in patients with no known risk factors.5 The adequate intake for ages 50 to 70 is 10 mcg/day (400 IU)
and for over age 70 is 15mcg/day (600 IU) with a safe
upper limit of 500 mcg/day (2000 IU).
Safety of Calcium Supplements
The health hazards of exposure to lead are well known. In
recent years, much attention has been paid to the fact that
calcium carbonate supplements contain trace amounts of
lead. In one recent study, 4 of the 7 popular over-the-counter calcium carbonate supplements tested contained lead
(~1mg/day for 800 mg/day of calcium and 1-2 mg/day for
1500 mg/day of calcium). 1
Whether or not such levels of exposure are a threat to
health is an open question. Calcium is known to offset the
effects of lead by blocking its absorption (both in the supplement and in other dietary contributors of lead).2 In fact,
research has shown that blood lead levels are lower in people who take calcium supplements than in those who do
not.3 As a consequence, Robert P. Heaney, MD, of
Creighton University, a leader in the field of calcium and
bone, has written, “the calcium sources available today are
generally very safe.”2
Vitamin A (retinol). The deleterious effects on bone of
high levels of vitamin A (as retinol) are well characterized, including reduced bone mass and increased fracture
rates.6 A recent analysis of the Nurses’ Health Study data
involving 72,337 postmenopausal women from 1980–98
looked at associations between intake of retinol and hip
fracture. The analysis found the risk of hip fracture nearly doubled in women not on hormone-replacement therapy who had retinol intakes of +2000 mcg/day (6700 IU)
as compared with intakes under 500 mcg/day (1650
IU).7 Vitamin A from beta carotene was not found to contribute significantly to increased fracture risk.7 The recommended dietary allowance for vitamin A is 900
mcg/day (3000 IU) for men and 700 mcg/day (2300 IU)
for women with a limit of 3000 mcg/day (10,000 IU).
Liver, fish oil, whole-milk dairy products, eggs, and fortified foods such as margarine are dietary sources of
vitamin A.
In short, patients are safe taking calcium supplements from
respected manufacturers. Patients should, however, avoid
supplements derived from dolomite, bone meal, or unrefined oyster shell. Alternatives to calcium carbonate
include calcium citrate, calcium phosphate, and (by prescription) calcium acetate. Be advised that calcium carbonate preparations are
currently the least expensive and the most widely available.
1. Ross EA, Szabo NJ, Tebbett IR. Lead content of calcium supplements. JAMA.
2000;1425-1429.
2. Heaney RP. Lead in calcium supplements: cause for alarm or celebration? JAMA.
2000;284:1432-33
3. Muldoon SB, Cauley JA, Kuller LH, Scott J, Rohay J. Lifestyle and sociodemographic
factors as determinants of blood lead le vels in elderly women. Am J Epidemiol.
1994;139:599-608.
Vitamin C. The recommended intake for vitamin C is
90 mg/day for men over 50 and 75 mg/day for women
over 50 with a tolerable upper limit of 2000 mg/day.
Higher intake of vitamin C (~100-125 mg/day) has been
linked in some studies to reduced hip fracture risk and
increases BMD in postmenopausal women. 8, 9, 10 This
effect was found to be stronger in women with high
calcium intakes.10
Dietary sources of calcium include dairy products (milk,
yogurt, and cheeses); fortified juices, breads, and cereals;
nuts and seeds; fish eaten with bones (sardines, salmon);
soy milk and tofu processed with calcium salts; green
vegetables, such as turnip greens, broccoli, and collards;
beans, such as chick peas and soy beans; and some fruits,
such as oranges, raisins, and dried figs.
Research into the effect of vitamin C on BMD is not
conclusive, and contrary results have been found. 11
Animal studies suggest that a very high intake of vitamin
C (i.e., 2000 mg/day or more) may accelerate bone loss
and increase the risk of kidney stones.
Achieving bone-building and bone-preserving effects of
pharmacologic therapies for osteoporosis requires adequate calcium intake.
Dietary sources of vitamin C include citrus fruits and
fruit juices; other fruits, such as cantaloupe and strawberries; and some vegetables, such as potatoes, cabbage,
peppers, and broccoli.
Vitamin D. Vitamin D regulates intestinal calcium
absorption and helps mineralize bone. The most readily
available source of vitamin D is direct sunlight. However,
people are often encouraged to avoid sunlight because of
skin cancer and wrinkles, and the skin’s ability to metabolize vitamin D diminishes with age. Other sources of vitamin D include fish liver oils, fatty fish, eggs, liver, and
fortified foods such as milk and cereal.
Vitamin K. The recommended daily intake of vitamin K
is 120 mcg/day for men and 90 mcg/day for women, with
no established upper limit. Besides being essential to
blood clotting, vitamin K is necessary for making a protein, osteocalcin, involved in bone formation. Vitamin K
❹
is made by bacteria in the intestinal tract and stored in the
liver. Food sources of vitamin K include fermented soy
and dairy products, fish, meat, liver, eggs, leafy greens,
brussel sprouts, cabbage, and plant oils. Patients with malabsorption syndromes or in whom intestinal bacteria have
been destroyed by antibiotic therapy should be monitored
for vitamin K deficiency. The role of vitamin K supplementation in osteoporosis therapy is as yet unclear. Studies
have suggested that vitamin K supplementation over the
recommended intake levels may have a positive impact on
bone mass in postmenopausal women.12, 13, 14 Research in
this area is ongoing.
(dark green) vegetables, whole grains, meats, milk,
bananas, nuts, and seeds. Because magnesium is found in
many foods, magnesium deficiency is uncommon but can
be found in patients with malabsorption conditions or
those on a limited diet.
Magnesium appears to affect bone remodeling, strength,
and preservation. However, the small number of welldesigned studies looking at magnesium intake and BMD
have to date yielded inconclusive results. Patients with
kidney disease should not take magnesium supplements.
Boron. There are currently no recommended daily intake
or average intake levels established for the trace element
boron.16 However, a tolerable upper limit has been established at 20 mg/day.17 Studies in rats have shown
increased bone mass with unchanged bone flexibility
following exposure to boron. In addition, a study in
humans found a positive impact on calcium metabolism in
postmenopausal women receiving supplemental boron of
3 mg/day. Common sources of boron are nuts, fruits,
milk, eggs, potatoes, vegetables, legumes, and pulses (e.g.
peas, beans, lentils).
Manganese, Copper, Zinc. The dietary minerals manganese, copper, and zinc are cofactors for enzymes
required for healthy bone metabolism.
There is currently no recommended daily intake for
manganese. Adequate intakes for men are 2.3 mg/day and
for women of 1.8 mg/day with a tolerable upper limit of
11 mg/day. Dietary sources of manganese include nuts,
legumes, tea, and whole grains.
The recommended intake of copper for adults is 900
mcg/day with an upper limit of 10000 mcg/day. Dietary
sources of copper include organ meats, seafood, nuts,
seeds, cereals, whole grains, and cocoa.
Fluoride. Fluoride is a trace element necessary for
growth of teeth and bone. There is no recommended daily
intake level. Adequate intakes are 4 mg/day for adult men
and 3 mg/day for adult women, with a tolerable upper
limit of 10 mg/day. Sodium fluoride has long been investigated as a possible defense against bone loss and osteoporosis. High doses (50+ mg/day) have been shown to
increase bone mass significantly, but do not reduce risk of
fracture, because the bone formed is brittle.18 Research
suggests that long-term low doses (~20-50 mg/day) of fluoride with calcium and vitamin D may have benefits for
BMD and reduced vertebral fracture risk.19, 20, 21 Since these
data are controversial, fluoride is not suggested for the
prevention or treatment of osteoporosis. Over-the-counter
fluoride preparations containing 1-2 mg were at one time
available. Currently, only topical gels and rinses for
dental health containing .01%-.1% concentrations are
available over-the-counter. Dietary sources of fluoride
include marine fish, teas, and fluoridated water.
The recommended intake of zinc for adults is 11 mg/day
for men and 8 mg/day for women with an upper limit of
40 mg/day, assuming that the person has normal kidney
function. Dietary sources of zinc include fortified cereals,
eggs, dairy products, nuts, red meat, peas, and certain
seafood. Patients with kidney disease should not take zinc
supplements.
Phosphorus. The recommended intake for phosphorus
is 700 mg/day for men and women, with an upper limit of
4000 mg/day until age 70, after which the safe limit drops
to 3000 mg/day. Dietary sources of phosphorus include
dairy products, meat, peas, eggs, and some cereals.
Phosphorous is also found in cola beverages and many
processed foods. It has long been known that excess phosphorus intake increases the need for calcium by interfering with calcium absorption. However, a recent study
found that phosphorous deficiency may reduce the
absorption of calcium and thereby lead to bone loss.15
Strontium. Strontium is a trace element found in sea
water. Its primary source in the diet is seafood. Other
sources include whole milk, wheat bran, meat, poultry,
and root vegetables. There are no recommended daily or
adequate intakes established for strontium. However, average daily intakes have been estimated to be about 1 to 3
mg. Research on animals has suggested that strontium
may increase bone strength. 22, 23 Human studies have also
suggested positive effects of strontium supplementation
on BMD.24, 25 However, high intakes of strontium have
been found to increase bone fragility and impair vitamin
D metabolism and bone mineralization.26
Magnesium. Magnesium is required for many enzyme
reactions as well as synthesis of proteins and nucleic
acids. Magnesium is needed for the secretion and action
of parathyroid hormone, an important regulator of calcium status.
The recommended daily intake for men is 420 mg and for
women is 320 mg. The safe upper limit for magnesium is
established at 350 mg/day from supplement/ pharmaceutical sources (not including food and water), if kidney function is normal. Sources include chlorophyll-containing
❺
Established Bone
Benefit
• Calcium
• Vitamin D
• Protein
Reading the Label
Since 1999, foods and dietary supplements have been
required to provide nutritional information on the product’s
ingredients.
Possible Bone Benefit
• Boron
• Copper
• Fluoride*
• Magnesium
• Manganese
• Omega-3 fatty acids
(non-retinol)
• Phosphorus
• Soy (isoflavones)
• Strontium+
• Vitamin C
• Vitamin K
• Zinc
A food’s “Nutrition Facts” panel indicates the amount of
calcium in the product in terms of percent daily value (%
DV). Dietary supplements usually have a “Supplement
Facts” panel that lists nutritional content both in terms of
% DV and milligrams or international units (IUs).
For the purpose of food/supplement labeling, the % DV for
calcium is 1000 milligrams. A food containing 30% DV for
calcium contains 300 mg of calcium per serving.
Keep in mind that to receive the calcium indicated on the
label, one must consume the appropriate size serving. For
example, let’s say a product’s Nutrition Facts panel indicates that it contains 1000 mg of
calcium “per serving,” and one “serving” is equal to 4
tablets. To receive 1000 mg of calcium, you must take 4
tablets. Consumers who do not read the label carefully may
only take 1 tablet, and only get 250 mg of calcium.
No Demonstrated Bone
Benefit
• Progesterone cream
Potential Harm to Bone
• Vitamin A from retinol
• High intake of fluoride
• High intake of oxalate
• High intake of phosphorous
• High intake of strontium
* Long-term, low-dose
fluoride only
+ Low-dose strontium only
Phytoestrogens and Omega-3 Fatty Acids.
Phytoestrogens are compounds found in plants that have
mild estrogenic or antiestrogenic effects on specific tissues in the body, depending on factors such as gender,
age, and hormonal status. There are two main categories
of phytoestrogens: isoflavones and lignans.
It’s essential for patients to understand labeling on food
and dietary supplements in order to effectively meet their
nutritional needs. For more information on nutritional
labeling, visit http://vm.cfsan.fda.gov/~dms/foodlab.html.
For more information on calcium, contact the National
Osteoporosis Foundation at www.nof.org.
An accumulating body of evidence suggests that high consumption of isoflavones (over 50 mg/day) has a beneficial
effect on the cardiovascular system and skeleton in postmenopausal women.30,31
Foods and Other Products
Dietary sources of isoflavones include soy, chick peas, red
clover, and legumes. Long-term clinical trials are needed
to assess the effectiveness of isoflavones on fracture rate
and BMD at various skeletal sites.
Omega-3, or n-3, polyunsaturated fatty acids come from
plant sources (lignans) or animal sources (fish oil).
Omega-3 fatty acids have been shown in animal and cell
research to have a beneficial effect on bone mass.32 In
ovariectomized rats, the beneficial effect has been shown
to increase with the addition of estrogen.32 To date, human
studies have not shown a similar benefit. Plant sources of
omega-3 fatty acids (lignans) include soybeans, flaxseed,
and walnuts. Animal sources of omega-3 fatty acids
include fatty fish (e.g., salmon, mackerel, and sardines).
Vegetable sources may be preferable to avoid detrimental
effects of retinol, found in high concentrations in fish oil.
(See above discussion on vitamin A.) Supplements are
widely available.
Protein. Recommended intake of protein is 63 grams/day
for adult men and 50 grams/day for adult women.27 A highprotein diet has been demonstrated to increase the body’s
need for calcium. Furthermore, a high-protein diet can
cause urinary loss of calcium. However, a three-year study
of 342 men and women over 65 found that in the presence
of 500 mg/day calcium and vitamin D supplementation, a
high-protein diet (average 79 grams/day) significantly
benefited bone density.28 Any association between protein,
osteoporosis, and fracture risk has not been fully explored.
On the other hand, low intake of protein has been linked to
low femoral neck BMD in institutionalized elderly.
Outcomes following hip fracture in such patients were significantly improved with protein supplementation, which
resulted in reduced bone loss from the hip.29
Oxalate. Oxalate, a nutrient found in some foods, including spinach, rhubarb, and sweet potatoes, binds with
calcium, disrupting absorption of the calcium in that food
(not in other foods). Oxalate intake is usually not a meaningful problem if daily calcium intake overall is adequate.
Progesterone creams. Clinical studies have reported
that progesterone applied topically as a cream is absorbed
into the body.33, 34 However because absorbed levels of
❻
progesterone observed in studies have been much lower
than levels achieved through oral or vaginal progesterone
therapies, the bone-health benefits of such therapies are
as yet uncertain. One randomized study looking at 102
women found no bone-protective effect at one year of
transdermal progesterone therapy (20 mg/day), but did
find vasomotor improvement in the treatment group.35
Associated risks to tissues such as the breast have yet to
be characterised. It may be advisable to monitor serum
levels in patients using progesterone creams.
12.Douglas AS, Robins SP, Hutchinson JD, Porter RW, Stewart A, Reid
DM. Carboxylation of osteocalcin in post-menopausal osteoporotic
women following vitamin K and D supplementation. Bone.
1995;17(1):15-20.
13.Knapen MH, Hamulyak K, Vermeer C. The effect of vitamin K supplementation on circulating osteocalcin (bone Gla protein) and urinary
calcium excretion. Ann Intern Med. 1989;111(12):1001-5.
14.Sokoll LJ, Booth SL, O’Brien ME, Davidson KW, Tsaioun KI,
Sadowski JA. Changes in serum osteocalcin, plasma phylloquinone,
and urinary gamma-carboxyglutamatic acid in response to altered
intakes of dietary phylloquinone in human subjects. Am J Clin Nutr.
1997;65(3):779-84.
15.Heaney RP, Nordin BEC. Calcium effects on phosphorus absorption:
Implications for the prevention and co-therapy of osteoporosis. J Am
Coll Nutr.2002; 21(3):239.
16.Chapin RE, Ku WW, Kenney MA, McCoy H, Gladen B, Wine RN,
Wilson R, Elwell MR. The effects of dietary boron on bone strength in
rats. Fundam Appl Toxicol. 1997;35(2):205-15.
17.Neilsen FH, Hunt CD, Mullen LM, Hunt JR. Effect of dietary boron on
mineral, estrogen, and testosterone metabolism in postmenopausal
women. FASEB J. 1987;1(5):394-397.
18.Marcus R, Feldman D, Kelsey J, Eds. Osteoporosis. Academic Press,
Inc. San Diego, 1996; 1373 pp.
19.Pak CYC, Sakhaee K, Adams-Huet B, Piziak V, Peterson RD,
Pointdexter JR. Treatments of postmenopausal osteoporosis with slow
release sodium fluoride. Ann Intern Med. 1995;123:401-8.
20.Reginster JY, Meurmans L, Zegels B, et al. The effect of sodium
monofluorophosphate plus calcium on vertebral fracture rate in post
menopausal women with moderate osteoporosis. Ann Intern Med.
1998;129(1):1-8.
21.Ringe JD, Kipshoven C, Coster A, Umbach R. Therapy of established
post-menopausal osteoporosis with monofluorophosphate plus calci
um: Dose-related effects on bone density and fracture rate. Osteoporos
Int. 1999;9(2):171-8.
22.Okayama S, Akao M, Nakamura S, Shin Y, Higashikata M, Aoki H.
The mechanical properties and solubility of strontium-substituted
hydroxyapatite. Biomed Mater Eng. 1991;1(1)11-17.
23.Buehler J, Chappuis P, Saffar JL, Tsouderos Y, Vignery A. Strontium
ranelate inhibits bone resorption while maintaining bone formation in
alveolar bone in monkeys (Macaca fascicularis). Bone.
2001;29(2):176-9.
24.Reginster JY. Miscellaneous and experimental agents. Am J Med Sci.
1997;313(1):33-40.
25.Reginster JY, Roux C, Juspin I, Provvedini DM, Birman P, Tsouderos
Y. Strontium ranelate for the prevention of bone loss of early
menopause. [Abstract] Osteoporos Int. 1998;8:12.
26.Schaafsma A. de Vries PJ, Saris WHM. Delay of natural bone loss by
higher intakes of specific minerals and vitamins. Crit Rev Food Sci
Nutr. 2001;41(4):225-49.
27.National Research Council, Ed. Recommended Dietary Allowances.
National Academy Press. Washington, DC. 1989.
28.Dawson-Hughes B, Harris SS. Calcium intake influences the association of protein intake with rates of bone loss in elderly men and
women. Am J Clin Nutr. 2002 Apr;75(4):773-9.
29.Schurch MA, Rizzoli R, Slosman D, Vadas L, Vergnaud P, Bonjour JP.
Protein supplements increase serum insulin-like growth factor-I levels
and attenuate proximal femur bone loss in patients with recent hip
fracture. A randomized, double-blind, placebo-controlled trial. Ann
Intern Med. 1998;128(10):801-9.
30.Scheiber MD, Liu JH, Subbiah MT, Rebar RW, Setchell KD. Dietary
inclusion of whole soy foods results in significant reductions in clinical
risk factors for osteoporosis and cardiovascular disease in normal postmenopausal women. Menopause. 2001;8(5):384-92.
31.Somekawa Y, Chiguchi M, Ishibashi T, Aso T. Soy intake related to
menopausal symptoms, serum lipids, and bone density in postmenopausal Japanese women. Obstet Gynecol. 2001 Jan;97(1):109-15.
32.Watkins BA, Li Y, Lippman HE, Seifert MF. Omega-3 polyunsaturated
fatty acids and skeletal health. Exp. Biol. Med. 2001;226(6):485-97.
33. Carey BJ, Carey AH, Patel S, Carter G, Studd JW. A study to evaluate
serum and urinary hormone levels following short and long ter m
administration of two regimens of progesterone cream in postmenopausal women. BJOG. 2000;107(6):722-6.
34.O’Leary P, Feddema P, Chan K, Taranto M, Smith M, Evans S.
Salivary, but not serum or urinary levels of progesterone are elevated
after topical application of progesterone cream to pre- and postmenopausal women. Clin Endocrinol (Oxf). 2000;53(5):615-20.
35.Leonetti HB, Longo S, Anasti JN. Transdermal progesterone cream for
vaso-motor symptoms and post-menopausal bone loss. Obstet Gynecol.
1999;94(2):225-8.
Summary
The Food and Drug Administration has limited regulatory
control of the over-the-counter vitamin, supplement, and
botanical industry. Oversight, such as it is, is restricted to
voluntary organizations that charge a fee for their review
and certification of a product. United States
Pharmacopeia (USP), Good Housekeeping Institute, and
Consumerlab.com are three such entities. There are efforts
on the part of these organizations to tighten and standardize their testing and certification procedures. However,
the bottom line is still “buyer beware.” Additional information on non-FDA approved therapies is available from
the National Institutes of Health’s National Center for
Complimentary and Alternative Medicine at
http://altmed.od.nih.gov. In addition, consumer information on nutrition and dietary supplements is available at
the FDA Dietary Supplement Questions and Answers web
site at http://www.cfsan.fda.gov/~dms/ds-faq.html and the
federal government’s nutrition website at http://www.nutrition.gov.
References
1. Kanis JA. The use of calcium in the management of osteoporosis.
Bone.1999;24(4):279-90.
2. Reid IR, Ames RW, Evans MC, Gamble GD, Sharpe SJ. Long-term effects
of calcium supplementation on bone loss and fractures in postmenopausal women: A randomized controlled trial. Am J Med.
1995;98(4):331-5.
3. Riggs LB, O’Fallon MW, Muhs J, O’Connor MK, Kumar R, Melton JL.
Long-term effects of calcium supplementation on serum parathyroid hormone level, bone turnover, and bone loss in elderly women. J Bone Miner
Res. 1998;13(2):168-74.
4. Reid IR, Ames RW, Evans MC, Gamble GD, Sharpe SJ. Effect of calcium
supplementation on bone loss in postmenopausal women. N Engl J Med.
1993;328(7):460-4.
5. Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch
BT, Vamvakas EC, Dick IM, Prince RL, Finkelstein JS. Hypovitaminosis D
in medical inpatients. N Engl J Med. 1998;338(12):777-83.
6. Binkley N, Krueger D. Hypervitaminosis A and bone. Nutr Rev.
2000;58:138-144.
7. Feskanich D, Singh V, Willett WC, Colditz GA. Vitamin A intake and hip
fractures among postmenopausal women. JAMA. 2002;287:47-54.
8. New SA, Bolton-Smith C, Grubb DA, Reid DM. Nutritional influences on
bone mineral density: A cross-sectional study in premenopausal women.
Am J Clin Nutr.1997;65:1831-9.
9. Wang MC, Luz Villa M, Marcus R, Kelsey JL. Associations of vitamin C,
calcium, and protein with bone mass in postmenopausal MexicanAmerican women. Osteoporosis Int. 1997;7(6):533-8.
10.Hall SL, Greendale GA. The relation of dietary vitamin C intake to bone
mineral density: Results from the PEPI study. Calcif Tissue Int.
1998;63(3):183-9.
11.Leveille SG, LaCroix AZ, Koepsell TD, Beresford SA, Van Belle G, Buchner
DM. Dietary vitamin C and bone mineral density in postmenopausal
women in Washington State, USA. J Epidemiol Community Health.
1997;51(5):479-85.
Close this window to return to the exam.
➐