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Osteoporosis

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Nayak N.K., Khedkar C.C., Khedkar G.D. and Khedkar C.D. (2016) Osteoporosis. In: Caballero, B., Finglas, P.,
and Toldrá, F. (eds.) The Encyclopedia of Food and Health vol. 4, pp. 181-185. Oxford: Academic Press.

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 Author's personal copy
Osteoporosis
NK Nayak, MGM College of Physiotherapy, India
CC Khedkar, SMBT Institute of Medical Sciences & Research Centre, Nashik, India
GD Khedkar, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, India
CD Khedkar, College of Dairy Technology, Pusad, India
ã 2016 Elsevier Ltd. All rights reserved.
Introduction
Osteoporosis is a disease characterized by a loss of bone mass
(BM) and strength below the threshold level required for
mechanical support of normal activity, as well as an increased
occurrence of non-traumatic fractures. It is a disease that grad-
ually causes the bones to become fragile and break easily. It is a
metabolic bone disorder characterized by a diffuse decrease in
the amount of bone. It affects both men and women, mainly as
they grow older. Loss of BM occurs as a normal part of the
aging process; however, in the individual with osteoporosis,
the loss is so extensive that it falls below the threshold of a
fracture. By their 30s, most people begin to slowly lose more
bone than can be replaced. As a result, bones become thinner
and weaker in structure.
Osteoporosis is the most common disease in elderly
women, affecting millions of white women in the US. More
than 25 million Americans have osteoporosis, and 80% of
them are women. Women of northern European descent who
have an inadequate dietary calcium intake are at the greatest
risk of developing osteoporosis. Fractures that result from oste-
oporosis are a major and growing concern for public health
systems. As the population ages, the number of fractures
worldwide will double or triple in the next 50 years. Osteopo-
rosis causes 1.3 million fractures, with 500 000 vertebral,
250 000 hip, and 240 000 wrist fractures costing $10 billion
per annum. In addition to this direct expenditure on treatment,
enormous economic costs and incalculable losses occur in
terms of disability, pain, and premature death. Only about
25% of women over 45 years of age who sustain a hip fracture
regain prefracture mobility.
An increased risk of falling contributes to a high incidence of
fragility fractures in osteoporotic patients. Osteoporosis is likely
to be caused by complex interactions among local and systemic
regulators of bone cell function. The heterogeneity of osteopo-
rosis is due to differences in the production of systemic and local
regulators, enzymes that produce or inactivate local regulators,
changes in receptors, nuclear transcription factors, and signal
transduction mechanisms. An increase in the elderly population
is directly proportional to the number of cases of osteoporosis.
Historical Background
Osteoporosis has probably existed throughout human history,
but only recently – as the human lifespan increases – has it
become a major clinical problem. In the early nineteenth
century, Sir Astley Cooper – an English surgeon – noted the
lightness and softness of bones, which is observed in the more
advanced stages of life, making them prone to fractures. The
Encyclopedia of Food and Health http://dx.doi.org/10.1016/B978-0-12-384947-2.00507-9
The Encyclopedia of Food and Health, (2016), vol. 4, pp. 181-185
term osteoporosis was first coined by Johann Lobstein at about
the same time. Dr. Fuller Albright, an American physician and
endocrinologist in 1940, described the postmenopausal
osteoporosis, and proposed that it was the consequence of
impaired bone formation due to estrogen deficiency.
Furthermore, the concept of two forms of osteoporosis (one
related to estrogen deficiency at the menopause stage and the
other to calcium deficiency and aging of the skeleton) was
proposed. This was replaced by the more recent concept stating
that osteoporosis represents a continuum in which multiple
pathogenic mechanisms congregate to cause the loss of BM and
microarchitecture deterioration of the skeletal structure.
Hip fracture rates are the highest in Caucasian women
living in temperate climates. These rates are somewhat lower
in women from Mediterranean and Asian countries, and are
lowest in African women. Countries like Hong Kong have seen
significant increases in age-adjusted fracture rates in recent
decades, while those in western countries largely appear to
have reached a plateau. Within the last decade, genetic studies
have facilitated the identification of many of the regulatory
mechanisms that have been linked to osteoporosis.
Human Skeleton
The human skeleton is a collection of bones – held together by
ligaments, tendons, muscles, and cartilage – in which crystals
of calcium phosphate are embedded, providing a framework
for the body. It holds and protects the organs. The adult skel-
eton consists of 206 bones. A newborn has more than 300
bones, but many of these fuse together as a child grows into an
adult. Bones are of two types. First is cortical bone, also called
compact bone. With a hard outer layer making up to 80% of
the total BM, it gives white color to the bones. Second is the
trabecular bone, also called cancellous or spongy bone. This
forms the inside and makes up the remaining 20% of the total
BM. It is light and porous, and makes up most of the bone
material. This tissue also has space for blood vessels and bone
marrow. Both cortical and trabecular bone contribute to the
overall strength of a bone. The trabeculae function as a storage
site for calcium phosphate crystals. As osteoporosis progresses,
the cortex also thins and weakens. These bones can be injured
easily, even without a serious accident or fall. Fractures have
been known to result from an affectionate hug.
Bone Strength
Bone mineral density (BMD) is determined by the amount of
bone present in the skeletal structure, that is, the higher the
181
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182 Osteoporosis
BMD, the stronger the bones, and vice-versa. It is greatly influ-
enced by genetic factors which, in turn, are sometimes modified
by environmental factors and medications. Normally, BMD
accumulates during childhood and reaches a peak by around
age 25, which is maintained for about 10 years. After age 35,
both men and women normally lose 0.3–0.5% of their BMD per
year as part of the aging process. Estrogen is important in main-
taining BMD in women. When estrogen levels drop after men-
opause, loss of BMD accelerates. During the first 5–10 years after
menopause, women can suffer up to 2–4% loss of BMD per
annum. This can result in the loss of up to 25–30% of their BMD
during that time period. The accelerated bone loss after meno-
pause is a major cause of osteoporosis in women, referred to as
postmenopausal osteoporosis.
Osteoporosis: Role of Diet and Nutrition
Many nutrients and food components can potentially have a
positive or negative impact on bone health. They may influ-
ence bones by various mechanisms, including: alteration of
bone structure, the rate of bone metabolism, the endocrine
system, and homeostasis of calcium and possibly of other
bone-active mineral elements. Among the essential nutrients,
vitamins A, B, C, and K also play important roles in bone
health. Reduced levels of calcium, vitamins, estrogen, and
physical activity have been implicated in the increased inci-
dences of osteoporosis (Table 1).
Calcium
Calcium is one of the main bone-forming minerals, and an
appropriate supply to bones is essential at all stages of life.
Calcium is required for normal growth and development of the
skeleton; 99% of the calcium in the body is in the skeleton.
Table 1 Potential nutritional determinants of bone health
Beneficial factors
Nutrients
Calcium
Copper
Zinc
Fluoride
Magnesium
Phosphorus
Potassium
Vitamin C
Vitamin D
Vitamin K
B vitamins
n-3 fatty acids
Protein
Novel bioactive food compounds
Whey-derived peptides
Phytoestrogens
Nondigestible oligosaccharides (especially inulin-type fructans)
Source: Cashman, K. D. (2006). A prebiotic substance persistently enhances intestinal calcium absorption and increases bone mineralization in young adolescents. Nutrition Reviews
64:189–196.
The Encyclopedia of Food and Health, (2016), vol. 4, pp. 181-185
Inadequate calcium intake during childhood and adolescence
can impair bone development and may prevent the attainment
of optimal peak BMD during early adulthood. In older adults,
inadequate calcium intake accelerates bone loss and likely
contributes to the development of osteoporosis. Sufficient cal-
cium intake is critical to achieving optimal peak BMD, which
modifies the rate of bone loss associated with aging. Adequate
levels of calcium may slow the development of osteoporosis, as
it suppresses bone resorption and it promotes bone minerali-
zation/calcification – leading to the strengthening of the
bones. A very small amount of calcium is required for muscle
contraction, nerve impulse transmission, and other regulatory
functions of the body. Although the importance of calcium to
bone health is well-recognized, adequate calcium intake alone
is not enough to prevent bone loss; loss that could lead to
osteoporosis and osteoporotic fracture.
In addition to the amount of calcium in the diet, the absorp-
tion of dietary calcium in foods is also a critical factor in deter-
mining the availability of calcium for development and
management of bones. The calcium that is lost daily through
the urine, sweat, and feces must also be replaced by the calcium
from the skeleton. To prevent a reduction in BM, calcium intake
and absorption must balance calcium losses. With increasing
age, calcium absorption decreases, and is lower in women who
have osteoporosis than in women who do not have osteoporo-
sis. There is a need to identify the foods and the food ingredients
that may positively influence calcium absorption, and to ensure
the calcium’s bioavailability from these foods. This approach is
important for individuals who fail to achieve the recommended
dietary level of calcium, and for those with a low efficiency of
intestinal absorption of calcium.
The current recommended daily allowance of calcium is 1 g
a day. It is recommended that women after menopause
increase their calcium intake to 1.5 g a day to maintain calcium
balance. Calcium in food occurs as salts, or with other dietary
constituents in the form of complexes of calcium ions. Calcium
Potentially detrimental dietary factors
Dietary factors/nutrients
Excess alcohol
Excess caffeine
Excess sodium
Excess fluoride
Excess/insufficient protein
Excess phosphorus
Excess/insufficient vitamin A
Excess n-6 PUFA
 Author's personal copy
must be released in a soluble, and probably ionized, form
before it can be absorbed. The increased bone resorption that
occurs with reduced levels of calcium affects both cortical and
trabecular bone. The incidence of fractures occurring at sites
composed of substantial amounts of both cortical and trabec-
ular bone (the hip, pelvis, proximal humerus, and tibia)
increases slowly with aging until late in the life cycle, when it
rises exponentially.
Phosphorus
Phosphorus is an essential bone-forming element. Its adequate
supply is necessary throughout life. Both calcium and phos-
phorus are required for the appropriate mineralization of the
skeleton. A depletion of serum phosphate leads to impaired
bone mineralization and compromised osteoblast function. In
the case of very low birth-weight infants, the dietary intake of
phosphorus influences the risk of osteoporosis.
Magnesium
Magnesium is required for bone and mineral homeostasis, and
in bone crystal growth and stabilization. Magnesium intake has
been reported, in some of the studies, to be positively associated
with both BMD and bone resorption markers in middle-aged
women. Magnesium is one of the nutrients in fruits and
vegetables that contribute to an alkaline environment, which
may promote bone health by a variety of mechanisms, making it
difficult to examine the effects of magnesium alone.
Fluorine
Fluorosis causes joint stiffness, limb deformities, and staining
of the teeth. Due to naturally high levels of fluoride in drinking
water, fluorosis occurs in several parts of the world, such as
South Africa, Tanzania, and India. Because of its effects on
stimulating osteoblastic activity and inhibiting bone crystal
dissolution, there has been considerable interest in the use of
pharmacologic doses of sodium fluoride for the treatment of
osteoporosis. At levels below those associated with fluorosis,
and when combined with a low calcium intake, high fluorine
intake has been associated with widened bones, reduced BMD,
and osteoporosis of cortical regions of the skeleton—possibly
due to excessive urinary calcium excretion.
Vitamins
Vitamin D is synthesized in the skin when exposed to ultravi-
olet radiation from sunlight, and can be obtained from the
diet. Older people tend to have reduced endogenous produc-
tion of the vitamin for a variety of reasons, and they become
more dependent on dietary sources to maintain adequate vita-
min D status. Younger people also have a reliance on dietary
sources of vitamin D, especially if they have limited exposure
to sunlight or if they are dark skinned and are living outside of
the tropics. It is a well-established fact that marginal vitamin D
The Encyclopedia of Food and Health, (2016), vol. 4, pp. 181-185
Osteoporosis 183
deficiency is common, and it increases the risk of osteoporosis.
The active form of this vitamin increases the intestinal absorp-
tion of calcium and prevents urinary calcium loss. In the
absence of vitamin D, calcium absorption is not efficient
enough to satisfy the body’s needs, even when calcium intake
is adequate. Vitamin D deficiency contributes to accelerated
bone loss, increasing fragility, and also neuromuscular impair-
ment leading to the increased the risk of falling. Calcium and
vitamin D supplementation is now advocated as the basic
minimum for treatment of osteoporosis and secondary fracture
prevention in women several years after menopause.
Among the vitamins, thinning of the cortices and loss of
trabecular architecture are common features of stark vitamin C
deficiency. Ascorbic acid is a cofactor in the hydroxylation of
lysine and proline, and is therefore important in the cross-
linking of collagen fibers in bone.
Vitamin K is a cofactor in the gamma carboxylation
of glutamic acid, which is important in the production of
osteocalcin—one of the main noncollagenous proteins of
bone. Inverse relationships have been reported between low
vitamin K intake in older people, BMD, and the risk of fragility
fractures—possibly through an increase in the amount of
osteocalcin produced in its under-carboxylated and less fully
functional form.
It is reported that a high intake of vitamin A as retinol has
been associated with hip fracture in Sweden. There are studies
linking low intakes of vitamin B6 and other B-vitamins with
low BMC and hip fracture.
Estrogen
Estrogen has a protective effect on the bone by suppressing
resorption. Estrogen deficiency is a major contributory factor
to the development of osteoporosis in women, and hormone
replacement therapy (HRT) remains the mainstay for preven-
tion of bone loss in postmenopausal women. Deficiency of
estrogen causes bone loss after menopause in women in their
70s and 80s, as evidenced by the fact that estrogen treatment
rapidly reduces bone breakdown in these older women. This
effect occurs for several reasons. Estrogen improves calcium
absorption in the intestinal tract and decreases calcium loss
in the urine.
Increased levels of estrogen lead to elevated levels of vita-
min D in the circulatory system in healthy human subjects. The
hypothesis that the estrogen deficiency is critical to the patho-
genesis of osteoporosis was based initially on the fact that
postmenopausal women, whose estrogen levels naturally
decline, are at the highest risk for developing the disease.
Estrogen stimulates the production of calcitonin, which pre-
vents removal of calcium from the bone. The level of estrogen
required to maintain relatively normal bone remodeling in
older postmenopausal women is lower than that required to
stimulate classic target tissues, such as the breast and uterus.
Trabecular bone tends to be more sensitive than cortical
bone to changes in the level of estrogen. Decreased levels of
estrogen have been implicated in the high incidence of Colles’
and vertebral fractures noted in women. These sites are com-
posed primarily of trabecular bone. Clinical trials involving
older individuals at high risk for calcium and vitamin D
 Author's personal copy
184 Osteoporosis
deficiency indicate that supplementation of both can reverse
secondary hyperparathyroidism, decrease bone resorption,
increase BD, decrease fracture rates, and even decrease the
frequency of falling.
Proteins
Protein intake is a determinant of urinary calcium excretion.
Animal protein (which is rich in sulfur-containing amino
acids) contributes to an acidic environment, leading to higher
excretion of calcium in urine. High protein intakes have been
linked with hip fracture because the consumption of protein,
particularly in the form of meat and dairy products, is greatest
in countries where hip fractures are common. A low protein
intake was associated with the greatest bone loss. At present,
there is no firm evidence on which to base recommendations
about optimal protein intake for bone growth, or for the
prevention of osteoporosis.
Physical Activity
Physical activity enhances bone strength by optimizing BMD,
and improving bone quality reduces the risk of falling. Resis-
tance training increase BM and prevents age-related declines in
BMD. Bone atrophy with accentuated calcium losses has been
reported after periods of inactivity, either from prolonged bed
rest or from immobilization. The emphasis of physical exercise
programs in elderly osteoporotic patients should be on
improving muscle strength and balance. They should be
encouraged to participate safely in any activity in a frequent,
regular, and sustained manner. The exercises should be weight
bearing and easy to complete and should fit into their daily
routine. A program of walking, sitting, and standing exercises
(or water aerobics) can be recommended to start with, and
gradually increased to more rigorous activity. For patients with
an osteoporotic fracture, physical exercise programs can help
reduce pain and increase functional capacity. The program
should increase the patient’s ability to perform routine daily
activities while minimizing the risk of further fractures. For
patients with vertebral fractures, back flexion exercises have
been found to be harmful and to increase the risk of new
vertebral fractures. These patients will benefit from resistance
exercises that strengthen back extensor muscles.
Lifestyle
An inactive lifestyle or extended bed rest tends to weaken
bones. Cigarette smoking is bad for bones as well as the heart
and lungs. Similarly, excessive consumption of alcohol
increases the risk of bone loss and fractures.
Risk Factors for Osteoporosis
Low BMD is only one of several risk factors underlying osteo-
porotic fracture. Other factors include both skeletal and non-
skeletal factors. The BMD in the later portion of life of an
The Encyclopedia of Food and Health, (2016), vol. 4, pp. 181-185
individual depends on the peak BMD achieved during growth,
and the rate of subsequent age-related bone loss. Development
of maximal BMD during growth and reduction of loss of bone
later in life are the two main strategies of preventing osteopo-
rosis. Consequently, any factor that influences the develop-
ment of peak BMD or the loss of bone in middle-age will
affect later fracture risk. The factors like low BMD, physical
frailty, propensity to fall, and a history of fracture also appear
to be strong predictors of osteoporosis.
Those factors that influence the BMD are broadly grouped
into non modifiable factors (gender, age, body [frame] size,
genetics, and ethnicity) and modifiable factors (hormonal
status [especially sex and calciotropic hormone status], lifestyle
factors including physical activity levels, smoking and alcohol
consumption patterns, and diet). The interactions of these
genetic, hormonal, environmental, and nutritional factors
influence both the development of bone to peak BD at matu-
rity and its subsequent loss.
Symptoms of Osteoporosis
Osteoporosis is often called a silent disease because bone loss
occurs without symptoms. The lack of any symptoms may
continue for decades because osteoporosis does not cause
symptoms until a bone fractures. Patients may not be aware
of their osteoporosis until they suffer a painful fracture. The
symptom associated with osteoporotic fractures usually is pain
at the site of fracture. The symptoms in men are similar to those
in women. The disease remains unnoticed until the bones
become so weak that a sudden strain, bump, or fall causes a
hip to fracture, or a vertebra to collapse. Collapsed vertebrae
may initially be felt or seen in the form of severe back pain or
spinal deformities.
Diagnosis of Osteoporosis
The BMD refers to the amount of minerals in a specific area of
the bones. It gives an overall picture of bone health. A BMD test
compares the person’s results with the optimal peak bone
density of a healthy young adult of that sex. Tests are safe and
painless, with no needles or other invasive instruments.
Typically, the test is performed with a central dual energy
x-ray absorptiometry machine. It also may be done with com-
puted tomography or an ultrasound.
Treatment of Osteoporosis
A comprehensive treatment program includes a focus on proper
nutrition, exercise, and safety issues to prevent falls that may
result in fractures. Treatments with medication can be broadly
divided into two categories: antiresorptive (or anti-catabolic)
and anabolic agents. Antiresorptive drugs help slow bone loss,
and studies show they can decrease the risk of fractures.
Antiresorptive agents (which include oestrogen), selective
estrogen receptor modulators, and bisphosphonates reduce
bone resorption (and subsequently bone formation), preserv-
ing BMD. Anabolic agents, including full-length parathyroid
 Author's personal copy
hormone (PTH1-84) and teriparatide (PTH1-34), stimulate
bone formation (and subsequently bone resorption), thereby
increasing BMD. Strontium ranelate is another agent that
reduces fracture risk. It has weak effects on bone remodeling
and probably improves bone strength mainly through effects
on bone material properties.
HRT may consist of estrogens alone, or in combination
with progestin. Even at low doses, HRT helps to slow bone
loss, reducing the risk of osteoporosis and fractures in women
who have gone through menopause. HRT is safe and effective
for most women under the age of 60 who have osteoporosis
and who also need hormonal treatment to relieve the symp-
toms of menopause.
It was demonstrated in recent studies that HRT decreases
fragility fracture risk by 20–35%. However, its discontinuation
results in acceleration of bone turnover, decrease in BMD, and
eventual loss of anti-fracture efficacy. It was also reported that
even low doses of HRT protects bone turnover markers levels
and prevents bone loss. At present, HRT is regarded as the
acceptable treatment for osteoporosis only after all other treat-
ments have been considered, and when all the risks and ben-
efits have been carefully explained to the patient. It has also
been observed in some of the studies that the HRT can also
induce vaginal bleeding and breast tenderness.
Conclusion
Osteoporosis is a treatable disease and in some cases, prevent-
able. It is a complex, polygenic disorder. The contributions of
specific gene polymorphisms are likely to be relatively small,
but may still be clinically important. If treatment begins early,
patients can be spared pain and suffering, and will likely lower
the overall health cost incurred from treatment of osteoporosis
complications. Preventative and therapeutic treatment should
be given before signs occur, or as early in the disease as possi-
ble. To keep pace with the modern developments in research,
large cohort studies using standardized genotyping methodol-
ogy are needed to better define the role of specific genes in
pathogenesis of osteoporosis.
The Encyclopedia of Food and Health, (2016), vol. 4, pp. 181-185
View publication stats
Osteoporosis 185
See also: Alcohol: Metabolism and Health Effects; Calcium:
Physiology; Dahi; Dairy Products: Dietary and Medical Importance;
Fish: Dietary Importance and Health Effects; Milk: Role in the Diet;
Mushrooms and Truffles: Role in the Diet; Vitamins: Overview; World
Health Organization.
Further Reading
Baldock PA and Eisman JA (2004) Genetic determinants of bone mass. Current Opinion
in Rheumatology 16: 450–456.
Cashman KD (2006) A prebiotic substance persistently enhances intestinal calcium
absorption and increases bone mineralization in young adolescents. Nutrition
Reviews 64: 189–196.
Faienza MF, Ventura A, Marzano F, and Cavallo L (2013) Postmenopausal
osteoporosis: the role of immune system cells. Clinical and Developmental
Immunology 2013: 1–6, Article ID 575936.
Favus MJ (2010) Bisphosphonates for osteoporosis. The New England Journal of
Medicine 363(21): 2027–2035.
Kronenberg H and Kobayashi T (2004) Transcriptional regulation in development of
bone. Endocrinology 146: 1012–1017.
Lean JM, Jagger CJ, Kirstein B, Fuller K, and Chambers TJ (2005) Hydrogen peroxide
is essential for estrogen-deficiency bone loss and osteoclast formation.
Endocrinology 146: 728–735.
McNamara LM (2010) Perspective on post-menopausal osteoporosis: establishing an
interdisciplinary understanding of the sequence of events from the molecular level
to whole bone fractures. Journal of the Royal Society Interface 7(44): 353–372.
Rosen CJ (2005) Clinical practice. Postmenopausal osteoporosis. New England Journal
of Medicine 353: 595–603.
Tyagi AM, Srivastava K, Mansoori MN, Trivedi R, Chattopadhyay N, and Singh D (2012)
Estrogen deficiency induces the differentiation of IL-17 secretingTh17 cells: a new
candidate in the pathogenesis of osteoporosis. PLoS One 7(9): e44552.
Viljakainen HT, Natri AM, Karkkainen M, et al. (2006) A positive dose–response effect of
vitamin D supplementation on site-specific bone mineral augmentation in
adolescent girls: a double-blinded randomized placebo-controlled 1-year
intervention. Journal of Bone and Mineral Research 21: 836–844.
Relevant Websites
http://dx.doi.org/10.1172/JCI27071 – PubMed Central.
http://www.nof.org/osteoporosis/diseasefacts.htm – National Osteoporosis Foundation.
http://rheumatology.oxfordjournals.org/content/48/suppl_4/iv3.full – Oxford Journals.