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Introduction:
Osteoporosis is a disease of the
bone that results from the loss of
calcium and other materials from the skeleton, leaving bones
with altered structure, less density, and less strength. This
process results in an increased risk for fractures, which not
only affects quality of life but also may result in fatal
consequences.
The impact osteoporosis has on our society can hardly be
overstated. Among Caucasian women over the age of 50, 17% are
found to have osteoporosis, while an additional 42% can be
classified as having �low bone mass� (referred to as
osteopenia). In Caucasian men, 4% are osteoporotic, while
an additional 33% are osteopenic. These figures are somewhat
lower among other ethnic groups.
At present, 40% of women and 13% of men over the age of 50 are
expected to sustain a fracture in their lifetime due to low
bone mass. Annually, we see approximately 1.3 million
fractures due to osteoporosis in the United States, and in
1995, $13.8 billion dollars were spent on osteoporotic
fractures. This amount exceeds the annual cost of treating
asthma and is nearly that of the annual expense of treating
heart failure. Roughly half of all women over the age of 50
who sustain a hip fracture will lose their ability to function
independently, and women over the age of 65 have an
approximate 25% mortality rate within one year of fracturing
their hip. After menopause, a woman has a greater chance of
dying from the consequences of an osteoporotic fracture than
from breast, uterine, and ovarian cancer
combined.
Features of
Osteoporosis:
Osteoporosis is a silent illness.
It can be likened to high blood pressure or elevated
cholesterol levels, neither of which cause symptoms but can
result in an increased risk for heart attacks and strokes. In
the same way, osteoporosis causes no symptoms until it causes
complications � namely fractures.
The most common sites of osteoporotic fractures are the
vertebrae of the spine, followed by the hip and the wrist.
Osteoporotic fractures often occur with little to no injury.
They may occur spontaneously, after a fall, or following a
lifting injury.
Only 1/3 of all vertebral fractures cause symptoms and are
found incidentally on x-ray studies; the remainder can be very
painful. As vertebrae fracture, a loss of height commonly
occurs and may result in changes in posture and the commonly
described �dowager�s hump� along the upper back. Vertebral
fractures only result in a mild increase in mortality, and
wrist fractures have no effect on mortality, but both have a
significant impact on quality of life. Hip fractures, on the
other hand, significantly impair both quality of life and
survival, as mentioned above.
Risk factors for osteoporosis include female gender, Caucasian
or Asian race, advanced age, slender build, low dietary intake
of calcium, family history of osteoporosis, and smoking.
Other factors that can adversely affect bone density include
use of certain medications such as corticosteroids, hormonal
imbalances (low testosterone, elevated levels of hormones from
adrenal or parathyroid glands), and excessive alcohol intake.
Secondary causes of osteoporosis should be sought in younger
individuals or males found to have low bone mass.
Diagnosis:
The most accurate and widely
available method for detecting osteoporosis is known as
bone densitometry. Techniques used for bone densitometry
vary and may include quantitative computerized tomography (CT)
and ultrasound, but the most commonly used modality is
dual-energy x-ray absorptiometry (DEXA).
A
DEXA scan is quick, painless, involves minimal radiation
exposure, and yields valuable information concerning bone
density and subsequent fracture risk. The spine and hip are
the most common areas imaged, but certain machines have the
capability of measuring bone density in the wrist or
calculating a total body measurement. For the most part,
however, assessing bone density of the spine and hip is
sufficient to screen for osteoporosis.
Two numbers are calculated from a DEXA scan: a T-score,
which compares bone density to young adult female averages,
and a Z-score, which compares a patient to averages for
the same age, gender, and race. It is the T-score that is
used to diagnose osteoporosis. A T-score of < -2.5 is
classified as osteoporosis, while a score of -1.0 to -2.4 is
considered osteopenia, and anything above -1.0 is normal.
There are many reasons that the Z-score is less useful; for
example, a �normal� bone density reading for an 80 year old
female imparts a significant risk for fracture. The Z-score
may be most useful when <-2.0, which suggests that a secondary
cause of low bone mass needs to be investigated.
Quantitative CT is less commonly employed and can only provide
information about bone density in the spine, but this method
eliminates the problem of bone spurs, which may falsely
elevate bone density readings on a DEXA scan. Some DEXA
machines are now equipped with software to perform lateral
vertebral measurements and this too may minimize this
problem. Ultrasound is performed on the heel, is very rapid,
inexpensive, and can estimate fracture risks at other sites.
Because ultrasound values correlate poorly with those
performed at other sites, however, pursuing a formal DEXA
study is usually recommended when making decisions about
therapy.
Bone density measurement is recommended for: 1) all
individuals with �low energy� fractures (simple falls, etc.),
2) women entering menopause with additional risk factors for
osteoporosis, 3) all women over the age of 65, 4) men over the
age of 70, 5) those planning long-term steroid therapy or
other medications that may cause bone loss, 6) those making
decisions about whether to start therapy to prevent bone loss,
and 7) monitoring the effects of therapy for low bone mass.
Plain x-rays may demonstrate evidence for prior fractures and
can demonstrate bones that appear less dense, but by the time
these changes are detectable by x-rays alone, a substantial
amount of bone mineral has already been lost. For this
reason, plain x-ray alone is a poor screening tool for
osteoporosis and is not recommended.
Therapy:
Treating osteoporosis involves stopping the
net loss of bone mineral that is occurring. Osteoporosis
occurs when more material is being taken away, or resorbed,
from bone that what is being put into the bone. If we can
slow down bone mineral being taken away (resorption) or
increase bone mineral being added (formation), bone
density will increase.
Decisions about the intensity of therapy are typically best
made on the basis of DEXA or other bone density measurements.
In an individual who is felt to be at low risk for ongoing
loss of bone density and who has a T-score of >-1.0,
maintaining an adequate intake of calcium and vitamin D is
sufficient. For those with relatively normal bone density or
mild osteopenia who have other risk factors for osteoporosis
or fractures to develop, an additional medication to help
prevent future loss of bone mass is prudent. For those with a
T-score of < -2.0, those with additional risk factors
and a T-score of < -1.5, or those with existing
fragility fractures, more aggressive treatment is indicated.
Exercise has
beneficial effects on bone density by stimulating �remodeling�
of bone. Low-impact activities such as walking or gentle
running are preferred. Exercise has the additional benefit of
improving muscle tone, which helps prevent falls.
Calcium and vitamin D supplementation
is the first step in treating and preventing osteoporosis.
During years of skeletal growth until peak bone mass is
achieved around the age of 35, an adequate calcium intake of
1,000 mg/day and vitamin D 400 units/day is important to build
strong bones. The first few years after menopause are
characterized by rapid loss of bone mineral, and at that point
1,200 to 1,500 mg/day of calcium and 400 to 800 units of
vitamin D are recommended. Similar recommendations are made
for those taking corticosteroids and older men.
Dairy products and some orange juice preparations are good
dietary sources of calcium, while carbonated beverages with
high phosphate content generally result in loss of calcium
from bones. Calcium supplements over the counter containing
calcium carbonate or calcium citrate in combination with
vitamin D provide additional protection. If added to a
reasonable diet, 2 to 3 tablets of a calcium and vitamin D
combination supplement are usually sufficient to provide for
one�s daily needs. While some brands of calcium may attempt
to claim superiority over others, it is not so much the form
of calcium but the amount of calcium that is important.
Estrogen replacement
therapy, given in form of pills or patches, prevents the loss
of bone mineral that occurs after menopause, and when begun
after the age of 65 may increase bone density by as much as
5-10%. Studies have documented lower vertebral fractures and
suggested lower hip fracture rates in women taking estrogen.
Recent widely publicized data, however, has shown an increased
risk of blood clots and heart attacks in women taking
estrogen, particularly in those with other risk factors such
as smoking. There has also been a longstanding concern about
the risk of breast cancer with estrogen. When this
information became available, many women stopped taking their
estrogen preparations without discussing this matter with the
prescribing physician. The unfortunate consequence of this
decision is that bone density drops rapidly after estrogen is
discontinued. Women should have a frank discussion with their
doctors about the pros and cons of taking estrogen as well as
alternatives to such therapy to prevent bone loss and the
complications that may result if no bone protective therapy is
being given.
Bisphosphonates are
medications that powerfully inhibit resorption of bone. By
doing so, bone density increases over time. Currently
available medications in this class include alendronate (Fosamax)
and risedronate (Actonel). Both of these medications may be
given either once daily or once weekly in pill form, and
Fosamax is also available in liquid form. Both of these
agents increase bone density in both the spine and the hip,
but more importantly reduce fracture risk at both of these
sites by as much as 50% within 6 months of starting therapy.
Because these drugs must be well absorbed, they are taken on
an empty stomach first thing in the morning, and it is
recommended that no food or other medications be given until
at least 30 minutes later. Some individuals experience an
upset stomach or possibly even some damage to the stomach
lining, which is minimized by taking these drugs with a full
glass of water in the upright position. Patients with
strictures in their esophagus who have difficulty swallowing
pills may not be good candidates for the pill form of these
medications but could still take the liquid form of Fosamax.
Raloxifene (Evista)
is a medication that acts as a �selective estrogen
receptor modifier,� producing the positive effects of
estrogens on bone, while avoiding the negative effects of
estrogen on breast tissue and possibly avoiding the increased
risk of heart attacks from estrogen. Given in pill form once
daily without the requirement of an empty stomach, Evista has
been shown to increase bone density in both the spine and hip,
but has only been shown to reduce fractures in the spine. It
is possible that hip fractures are reduced as well, but
studies to date may not have included enough patients to
demonstrate such an effect. A small increase in blood clots
may be seen with Evista, but beneficial effects are seen in
cholesterol levels, and it is possible that this agent may
actually reduce the risk of breast cancer (studies to
confirm this effect are underway).
Teriparatide (Forteo)
is a derivative of a hormone in the body known as parathyroid
hormone (PTH). This hormone stimulates both bone formation
and bone resorption, and depending on how much is present,
bone density either increases or decreases. Forteo is
designed to favor bone formation, and is the only available
treatment for osteoporosis that works in this way (all other
medications work mostly to inhibit bone resorption). It is
given in a once daily injection and while costly, assistance
programs to Medicare recipients are readily available.
Forteo increases bone density in both the spine and the hip
but has only been shown to reduce vertebral fractures.
Moreover, this agent may become less effective when given
continuously for over 2 years. While many physicians hoped
that Forteo could be given in combination with bisphosphonates
for additional benefit, studies have shown no more benefit
when combining these therapies than when using either agent
alone.
Calcitonin is also a
hormone normally made by the body that blocks bone resorption.
It is most commonly given in the form of a nasal spray once
daily and is associated with minimal side effects. The gains
in bone density seen with this agent, however, are less than
what are seen with other therapies and beneficial effects are
only observed in the spine. Nonetheless, vertebral fractures
are reduced when using this medication long-term and it does
have a role in treating osteoporosis in patients unable to
take other medications.
Novel agents in
development for treating osteoporosis include zoledronic acid,
strontium, osteoprotegerin, and inhibitors of RANK-ligand.
Zoledronic acid is an intravenous bisphosphonate similar to
Fosamax and Actonel. The advantage of this therapy is that it
can be given once a year and seems to have a prolonged effect
on inhibiting bone resorption. Thus far, studies have yet to
document a beneficial effect on reducing fractures. Strontium
is a medication given orally that both increases bone
formation while decreasing resorption. This agent appears to
increase bone density in the spine and the hip as well as
reducing vertebral fractures. Both osteoprotegerin and RANK-ligand
inhibitors are in early stages of development but appear to be
involved in the balance between bone formation and resorption,
representing another method for reducing fractures.
Vertebroplasty and
kyphoplasty are procedures that are now available for
treating symptomatic vertebral compression fractures. Both
involve the insertion of a catheter into the collapsed
vertebra under x-ray guidance. With vertebroplasty, a
cement-like material is injected into the vertebra to provide
stability and reduce pain, while kyphoplasty involves first
inflating the vertebra with a balloon before injecting with
cement. Kyphoplasty has the additional benefit of improving
postural changes, but is not clearly superior to
vertebroplasty alone in improving outcomes. When using these
methods, experienced centers are necessary, and after
completion of these procedures, it is essential to pursue
medical therapy to prevent future fractures.
Monitoring the effects of therapy is necessary to determine
whether the medication is having its desired effect on bone
density. DEXA scans performed every 1 to 2 years are usually
adequate to assess whether bone density is being maintained,
or hopefully increased. While important, increases in bone
density explain only a fraction of fracture reduction in
patients on certain therapies (bisphosphonates, for example).
Small gains in bone density may result in large reductions in
fracture risk.
Because of the time needed to see a meaningful change in bone
density, urine markers of �bone turnover� are available and
may demonstrate positive effects within a few months of
beginning osteoporosis therapy. The most common test run is a
urinary �N-telopeptide,� which is best collected on the second
urination of the morning. This level is often elevated in
those with ongoing risk for future loss of bone density but is
suppressed when medications designed to inhibit resorption
have their desired effect.
Because osteoporosis therapy has to be given continuously over
long periods of time and does not typically result in
improvement in symptoms, it is often difficult to encourage
patients remain on their medications. Adherence to the plan
of treatment, however, prevents complications and should
result in a greater overall quality, and perhaps duration, of
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