What are osteoporosis?

Causes and Symptoms

Bone is constantly being remodeled by cells: old bone is reabsorbed by the
osteoclasts, and new bone is formed by the osteoblasts.
Several factors control these processes of bone
formation and resorption, which are about equal in adults. In
children, formation exceeds resorption, and the bone mass increases. In old age,
however, bone resorption exceeds bone formation and bone mass is lost. When bone
mass is reduced, the bone becomes mechanically weak and vulnerable to fractures.
This condition of reduced bone mass is known as osteoporosis and is part of the
aging process. At this time, there is no known cure for osteoporosis. Prevention
is the only strategy for combating bone mineral loss and the development of
osteoporosis. A balanced diet including adequate calcium and vitamin D intake as
well as regular weight-bearing and muscle-strengthening exercises can prevent bone
loss.

Type I osteoporosis is related to aging alone. It has two forms: postmenopausal
(occurring in women between the ages of fifty-one and sixty-five) and senile
(occurring in both men and women past the age of seventy). Type II osteoporosis is
associated with an underlying disease such as hyperparathyroidism or
multiple
myeloma and may occur in younger as well as older
individuals. A third type has been found in young women who are amenorrheic
(having no menstrual cycles) in association with eating
disorders such as anorexia nervosa. Osteoporotic
fractures are occurring in women in their twenties and thirties who have been
amenorrheic for several years. Because it was found in athletic women, the link
between eating disorders, amenorrhea, and osteoporosis was named
the Female Athlete Triad. No matter the type of osteoporosis, it remains a
clinically silent disease and is usually asymptomatic until a fracture occurs. The
frequency of osteoporosis and related fractures is expected to increase in
parallel with the increase in the older population. Women are more vulnerable to
this condition, especially after the menopause. As the life span for men
increases, however, so will their risk for osteoporosis.

In the early postmenopausal period, the distal end of the radius and ulna (wrist)
are particularly susceptible to fractures; a few years later, the patient is
likely to sustain vertebral fractures. The most common presentation of such a
fracture is a sudden onset of very severe, localized back pain,
often occurring spontaneously. The pain is so severe that it incapacitates the
patient and may require the administration of narcotics for relief. Unlike the
pain caused by a disk rupture, this pain does not radiate to the legs, although
some radiation anteriorly may be present. The pain usually lasts about four weeks
and is then spontaneously relieved unless nerve compression or secondary arthritic
changes complicate the condition.

When multiple vertebrae have collapsed, the body height is reduced and the
patient’s arms appear to be disproportionately long. Normally, both
measurements—body height and arm span—are equal. In osteoporosis complicated by
several vertebral fractures, body height is reduced, but the arm span is
unchanged. When multiple thoracic vertebrae collapse, kyphosis (an
increased spinal curvature) develops. The space between the ribs and the pelvic
cavity is also reduced. When lumbar vertebrae are collapsed, the lower end of the
ribs may lie over the pelvic cavity. At this stage, the patient’s lung functions
may be compromised because the chest movements are limited. Pneumonia is
a common, sometimes fatal complication.

Progressive and long-standing osteoporosis may be complicated by fractures of the
femoral neck. Although most of these fractures are preceded by a fall, it is
probable that in some cases the bones are so weakened and fragile that they
fracture spontaneously and cause the patient to fall. Fractures of the femoral
neck are associated with significant mortality and morbidity risks, with 12 to 20
percent of the patients dying within six months of the fracture and about half
losing the ability to live independently.

A number of factors predisposing an individual to osteoporosis have been
identified. Some of these factors cannot be changed. For example, advanced age
increases the risk of developing osteoporosis. Furthermore, although both sexes
are affected by osteoporosis, women tend to be more vulnerable because, in
addition to the accelerated rate of bone loss that occurs after menopause, women
tend to have smaller skeletons than men do and, therefore, are likely to reach the
threshold at which bone fragility is increased well before men do. Caucasians and
Asians are more susceptible to osteoporosis than are Africans or Latinos, in whom
this condition is relatively rare. The reasons for these racial differences are
not well known. Finally, people with large body frames are less likely to develop
osteoporosis than those with small body frames, probably because their bone
reserve allows them to lose bone for a longer period before reaching the threshold
at which the bone fragility is significantly increased. Genetic research has also
determined that variations in the gene for the vitamin D receptor (VDR) may
contribute to 7 to 10 percent of the difference in bone mass density because of
its influence on calcium intake. For those with a family history of osteoporosis
or hip fracture, this factor could lead to identification of an individual’s risk
factor and enable early intervention.

A number of risk factors that can be reversed have also been identified. A low
dietary calcium intake is associated with a reduced bone mass and an increased
fracture rate. Conversely, an elevated calcium intake, particularly before
puberty, is associated with an increased mass. In 1994, the US National Institutes
of Health consensus statement recommended an increase in daily calcium, and in
1997 the National Academy of Sciences’ recommended dietary allowance (RDA)
increased from 800 milligrams per day to 1,300 milligrams at age nine up to age
eighteen. Men from age nineteen to seventy years should take in 1,000 milligrams,
increasing to 1,200 milligrams at age seventy-one. Women from age nineteen to
fifty should take in 1,000 milligrams, increasing to 1,200 milligrams after the
age of fifty-one. Higher doses may be detrimental, as they may cause the formation
of kidney stones, so the benefit must be weighed against the risk in each case.
Getting the greatest percentage of the calcium from the diet is preferred, but, if
it is to be taken as a supplement, no more than 500 milligrams should be taken at
one time and always with meals. Calcium is not absorbed well, so having stomach
acid present, as well as vitamin D and protein, enhances the absorption. Vitamin D
deficiency and excess vitamin A intake are also risk factors for the development
of osteoporosis.

Physical inactivity is associated with a reduced bone mass and therefore an
increased predisposition to developing osteoporosis. There is also evidence that
people who have a sedentary lifestyle are more susceptible to osteoporosis than
those who are physically active. During the formative years, exercise is
imperative to develop the highest bone density possible. Then throughout the rest
of life, exercise is essential to slow the rate of bone loss, particularly
weight-bearing and muscle-strengthening exercises. Several factors modulate the
response of the skeleton to exercise. These include the subject’s age and gender;
the intensity, frequency, and type of exercise; and the subject’s endocrinal
status. The current recommendation for exercise in relationship to osteoporosis is
preventive: a variety of exercise, both weight-bearing and vigorous, to be done
regularly (thirty to sixty minutes per day, three to five days per week)
throughout life. Variety is essential because no single exercise stresses all
bones equally. The stimulus to build bone comes from the muscle that is attached
to the bone pulling on the attachment site, which makes the bone remodel itself to
resist the stress.

In the elderly, exercise may have a secondary benefit. Often, a fracture is
precipitated by a fall, and the cause of the fall may be a loss of balance or
coordination. Maintaining an active lifestyle helps with balance and coordination,
all of which may help in the prevention of a fall. Studies in the elderly have
demonstrated that a general exercise such as walking is not enough to maintain
gains in bone density in the long term. Exercise studies of one or two years’
duration show a decline begins after about one year. To combat that loss, a
regular strength training regimen, targeting the most common fracture sites, done
two or three times a week for twenty minutes to stimulate specific bones, should
be added to any other activities that are done.

Cigarette smoking is associated with osteoporosis; however, the underlying
mechanism is not clearly understood. It is possible that cigarette smokers are
more likely to lead a sedentary life and have a reduced dietary calcium intake
compared to nonsmokers. Cigarette smoking may have a direct effect on the bone
cells, or it may have an indirect effect by modulating the release of substances
that may affect the activity of these cells, such as the parathyroid hormone or
calcitonin secretion. Smoking cessation is highly recommended
to reduce one's risk of developing osteoporosis. Alcohol abuse
is also a risk factor for the development of osteoporosis, and cirrhosis of
the liver further increases an individual's risk for osteoporosis. Excessive
alcohol intake should be avoided.

A number of drugs may induce osteoporosis. These include long-term anticoagulation
medications, hormonal therapies, glucocorticosteroids, some immunosuppressants,
lithium, thiazolidinediones (glitazones), and long-term proton pump inhibitor use.
For a person at risk for osteoporosis, anytime that medications are prescribed,
calcium interaction should be considered.

A number of diseases and disorders are associated with osteoporosis, including
genetic factors such as cystic fibrosis, hemochromatosis, and porphyria. Endocrine
disorders associated with osteoporosis include hyperparathyroidism, anorexia
nervosa, diabetes
mellitus, Cushing syndrome, and excess thyroid hormone.
Gastrointestinal disorders such as celiac disease, Crohn disease, cirrhosis, and
malabsorption can increase the risk of osteoporosis.
Rheumatoid arthritis and hematologic disorders such as multiple myeloma,
thalassemia, and leukemia also put individuals at risk of developing
osteoporosis.

Treatment and Therapy

Several tests are available to confirm the diagnosis of osteoporosis, quantify its degree, and identify underlying diseases that might cause or aggravate the osteoporosis.

X-rays used to be the only way to evaluate patients with osteoporosis. Although
they are helpful in assessing bone involvement from other diseases, they are not
useful for the detection of early osteoporosis because the characteristic
appearances are seen only when at least 40 percent of the bone mass has been lost.
In the 1990s, a new analysis technique was developed using a simple X-ray of the
hand and then computer analysis. It is able to reveal as little as 1 percent bone
loss.

The most accurate technique now available to measure bone density uses a technique
called dual energy X-ray absorptiometry (DEXA). DEXA is based on the principle
that if a beam of radiation is directed at a bone, the amount of radiation trapped
by the bone is proportional to the amount of mineral and calcium inside. By
knowing the amount of radiation aimed at the bone and the amount reaching a
detector crystal across the bone, the amount of mineral can be calculated. To
differentiate the radiation trapped by the surrounding muscles and fat from the
radiation trapped by the bone itself, radiation with two different peaks (which
are absorbed to a different extent by bone and soft tissue) is used. The exposure
to radiation is minimal, one-fiftieth the radiation as in a chest X-ray. The same
densitometry machine can do whole-body or single-site readings, making it even
more useful for diagnosis.

Osteoporosis therapy includes several options. Several drugs are currently being
used or investigated for use. Bisphosphonates are usually the first-line choice
when pharmacological therapy is indicated. Bisphosphonates include alendronate,
ibandronate, risedronate, and zoledronic acid. Parathyroid hormone (teriparatide)
delivered subcutaneously may also be a first-line treatment choice among patients
with the highest risk for fracture. Teriparatide works by increasing the action of
osteoblasts and causes bones to become denser and more resistant to fractures.
Other medications such as estrogen receptor modulators (raloxifene, lasofoxifene,
tibolone) are recommended for postmenopausal women with osteoporosis.

Calcitonin, a hormone produced by the thyroid gland, specifically inhibits
the osteoclasts, which are the bone resorbing cells. As a result, there is a
relative increase in the rate of bone formation, and the bone mass increases.
After the initial increase, however, the bone mass tends to stabilize, and the
continued administration of calcitonin beyond this point may be associated with an
actual decline in bone mass. Therefore, the risks of calcitonin may outweigh the
benefits.

Calcium supplements are useful if the patient’s dietary calcium intake is less
than recommended. Similarly, if the daily vitamin D intake is below the
recommended level of 600 to 800 international units in the elderly population,
supplementation is recommended. Vitamin D supplements may also be necessary in
patients who are taking a medication that interferes with vitamin D metabolism. An
excessive vitamin D and calcium intake, however, may lead to the development of
kidney stones.

Several nonpharmacological treatments may also improve quality of life and
functional status in persons with osteoporosis. Progressive quadriceps strength
and proprioception training and balance training are associated with a decrease in
falls in postmenopausal women with osteoporosis. Pilates and weight-bearing
exercises may also improve function in persons with osteoporosis, and tai chi may
improve balance and lessen the risk of falls.

Perspective and Prospects

The early diagnosis of osteoporosis and the ability to quantify its degree have
represented major strides in the diagnosis, management, and prevention of this
disease. It is now recommended that all women approaching the menopause be checked
to determine a baseline bone density reading and to help with prevention and
possible treatment options. Indeed, physicians can now identify patients with
early osteoporosis and assess their response to treatment accurately.
Additionally, modifiable risk factors increasing the likelihood of developing
osteoporosis have been identified; these include a low dietary calcium and vitamin
D intake, cigarette smoking, excessive alcohol use, anorexia nervosa or bulimia
nervosa, and a sedentary lifestyle. Education of the public, therefore, has an
important part to play in the prevention and management of osteoporosis.

Working with young people may be the best way to combat osteoporosis. For many
people, making the right choices early in life may have great influence in
preventing this debilitating disease later in life. For the older adult, attempts
are being made to develop “risk profiles” that can be used to estimate the
individual patient’s fracture risk. This in turn will allow physicians to identify
those in the population who are particularly likely to benefit from specific
therapy. Moreover, the increased understanding of bone formation, bone resorption,
and bone metabolism has led to a considerable amount of research work on the
development of effective treatment programs. Drugs that can build strong bones, or
ones that can prevent further bone loss, will need to be continually studied in
both men and women, and everything that can be done to reduce side effects from
these or other drugs that affect calcium stores in the bones must be a top
priority of research dollars spent.

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